Phenethyl isothiocyanate exhibits antileukemic activity in vitro and in vivo by inactivation of Akt and activation of JNK pathways

Effects of phenethyl isothiocyanate (PEITC) have been investigated in human leukemia cells (U937, Jurkat, and HL-60) as well as in primary human acute myeloid leukemia (AML) cells in relation to apoptosis and cell signaling events. Exposure of cells to PEITC resulted in pronounced increase in the activation of caspase-3, -8, -9, cleavage/degradation of PARP, and apoptosis in dose- and time-dependent manners. These events were accompanied by the caspase-independent downregulation of Mcl-1, inactivation of Akt, as well as activation of Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt by LY294002 significantly enhanced PEITC-induced apoptosis. Conversely, enforced activation of Akt by a constitutively active Akt construct markedly abrogated PEITC-mediated JNK activation, Mcl-1 downregulation, caspase activation, and apoptosis, and also interruption of the JNK pathway by pharmacological or genetically (e.g., siRNA) attenuated PEITC-induced apoptosis. Finally, administration of PEITC markedly inhibited tumor growth and induced apoptosis in U937 xenograft model in association with inactivation of Akt, activation of JNK, as well as downregulation of Mcl-1. Taken together, these findings represent a novel mechanism by which agents targeting Akt/JNK/Mcl-1 pathway potentiate PEITC lethality in transformed and primary human leukemia cells and inhibitory activity of tumor growth of U937 xenograft model

The Effect of Structural Complexity, Prey Density, and “Predator-Free Space” on Prey Survivorship at Created Oyster Reef Mesocosms

Interactions between predators and their prey are influenced by the habitat they occupy. Using created oyster (Crassostrea virginica) reef mesocosms, we conducted a series of laboratory experiments that created structure and manipulated complexity as well as prey density and “predator-free space” to examine the relationship between structural complexity and prey survivorship. Specifically, volume and spatial arrangement of oysters as well as prey density were manipulated, and the survivorship of prey (grass shrimp, Palaemonetes pugio) in the presence of a predator (wild red drum, Sciaenops ocellatus) was quantified. We found that the presence of structure increased prey survivorship, and that increasing complexity of this structure further increased survivorship, but only to a point. This agrees with the theory that structural complexity may influence predator-prey dynamics, but that a threshold exists with diminishing returns. These results held true even when prey density was scaled to structural complexity, or the amount of “predator-free space” was manipulated within our created reef mesocosms. The presence of structure and its complexity (oyster shell volume) were more important in facilitating prey survivorship than perceived refugia or density-dependent prey effects. A more accurate indicator of refugia might require “predator-free space” measures that also account for the available area within the structure itself (i.e., volume) and not just on the surface of a structure. Creating experiments that better mimic natural conditions and test a wider range of “predator-free space” are suggested to better understand the role of structural complexity in oyster reefs and other complex habitats

Systematic mechanical assessment of consolidants for canvas reinforcement under controlled environment

In conservation, adhesives are commonly used for the consolidation of canvases, yet their impact upon the canvas longevity has raised some concerns amongst conservators. As such, this study presents a testing protocol developed to assess the performance of commonly-used adhesives (natural animal glue and synthetic Beva® 371) and a newly developed nanocellulose consolidant, nanofibrillated nanocellulose (CNF). This includes their effect on the visual appearance, consolidation, and response of the mechanical properties of the treated canvases to programmed changes in relative humidity (RH). Scanning electron microscopy (SEM) images of animal glue- and Beva® 371-treated canvases revealed the presence of adhesive and consolidant on and in-between cotton fibres. The consolidants form bridges linking and connecting the cotton fibres and holding them together, whereas the CNF treatment, formed a visible continuous and dense surface coating. None of the treatments induced any discernible colour change. Controlled environment mechanical testing was performed in two ways: by applying a linearly increasing static force at fixed RH (Young’s modulus) and by applying a dynamic force together with a programmed RH cycling between 20 and 80% (RH dependent viscoelastic properties). CNF gave a higher value of Young’s modulus than either of the two commonly-used materials. Measurements at different values of RH (20 and 80%) demonstrated for all the treated canvases that at the lower value (RH 20%) Young’s modulus values were higher than at the higher value (RH 80%). Besides, the dynamic mode showed that the rate of response in all cases was rapid and reversible and that the nanofibrillated cellulose treated sample showed the highest variation in storage (or elastic) modulus measured at the end of RH plateaux (20 and 80% RH). Thus CNF appears to be a promising material given its higher mechanical performance. The protocol developed in this study has enabled us to examine and compare candidate materials for the consolidation of canvases systematically, using testing parameters that remained relevant to the field of canvas conservation

Orally available Mn porphyrins with superoxide dismutase and catalase activities

Superoxide dismutase/catalase mimetics, such as salen Mn complexes and certain metalloporphyrins, catalytically neutralize reactive oxygen and nitrogen species, which have been implicated in the pathogenesis of many serious diseases. Both classes of mimetic are protective in animal models of oxidative stress. However, only AEOL11207 and EUK-418, two uncharged Mn porphyrins, have been shown to be orally bioavailable. In this study, EUK-418 and several new analogs (the EUK-400 series) were synthesized and shown to exhibit superoxide dismutase, catalase, and peroxidase activities in vitro. Some also protected PC12 cells against staurosporine-induced cell death. All EUK-400 compounds were stable in simulated gastric fluid, and most were substantially more lipophilic than the salen Mn complexes EUK-189 and EUK-207, which lack oral activity. Pharmacokinetics studies demonstrate the presence of all EUK-400 series compounds in the plasma of rats after oral administration. These EUK-400 series compounds are potential oral therapeutic agents for cellular damage caused by oxidative stress

Allorecognition in the Tasmanian Devil (Sarcophilus harrisii), an Endangered Marsupial Species with Limited Genetic Diversity

Tasmanian devils (Sarcophilus harrisii) are on the verge of extinction due to a transmissible cancer, devil facial tumour disease (DFTD). This tumour is an allograft that is transmitted between individuals without immune recognition of the tumour cells. The mechanism to explain this lack of immune recognition and acceptance is not well understood. It has been hypothesized that lack of genetic diversity at the Major Histocompatibility Complex (MHC) allowed the tumour cells to grow in genetically similar hosts without evoking an immune response to alloantigens. We conducted mixed lymphocyte reactions and skin grafts to measure functional MHC diversity in the Tasmanian devil population. The limited MHC diversity was sufficient to produce measurable mixed lymphocyte reactions. There was a wide range of responses, from low or no reaction to relatively strong responses. The highest responses occurred when lymphocytes from devils from the east of Tasmania were mixed with lymphocytes from devils from the west of Tasmania. All of the five successful skin allografts were rejected within 14 days after surgery, even though little or no MHC I and II mismatches were found. Extensive T-cell infiltration characterised the immune rejection. We conclude that Tasmanian devils are capable of allogeneic rejection. Consequently, a lack of functional allorecognition mechanisms in the devil population does not explain the transmission of a contagious cancer

Etiological study of esophageal squamous cell carcinoma in an endemic region: a population-based case control study in Huaian, China

BACKGROUND: Continuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC). Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and food-borne carcinogens exposure, and XME polymorphisms in formation of ESCC, and to investigate possible gene-gene and gene-environment interactions associated with ESCC in Huaian, China. METHODS: A population based case-control study was conducted in 107 ESCC newly diagnosed cases and 107 residency- age-, and sex-matched controls in 5 townships of Huaian. In addition to regular epidemiological and food frequency questionnaire analyses, genetic polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX) were assessed from genomic DNA using PCR based techniques. RESULTS: Consuming acrid food, fatty meat, moldy food, salted and pickled vegetables, eating fast, introverted personality, passive smoking, a family history of cancer, esophageal lesion, and infection with Helicobacter pylori were significant risk factors for ESCC (P < 0.05). Regular clean up of food storage utensils, green tea consumption, and alcohol abstinence were protective factors for ESCC (P < 0.01). The frequency of the GSTT1 null genotype was higher in cases (59.4%) compared to controls (47.2%) with an odds ratio (OR) of 1.68 and 95% confidence interval (CI) from 0.96 to 2.97 (P = 0.07), especially in males (OR = 2.78; 95% CI = 1.22–6.25; P = 0.01). No associations were found between polymorphisms of CYP1A1, CYP1B1, CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05). CONCLUSION: Our results demonstrated that dietary and environmental exposures, some demographic parameters and genetic polymorphism of GSTT1 may play important roles in the development of ESCC in Huaian area, China

Growth Inhibition of Human Gynecologic and Colon Cancer Cells by Phyllanthus watsonii through Apoptosis Induction

Phyllanthus watsonii Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other Phyllanthus species, published information on the cytotoxicity of P. watsonii are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the P. watsonii extracts and fractions on human gynecologic (SKOV-3 and Ca Ski) and colon (HT-29) cancer cells. P. watsonii extracts exhibited strong cytotoxicity on all the cancer cells studied with IC50 values of ≤ 20.0 µg/mL. Hexane extract of P. watsonii was further subjected to bioassay-guided fractionation and yielded 10 fractions (PW-1→PW-10). PW-4→PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1→PPWH-8). PPWH-7 possessed greatest cytotoxicity (IC50 values ranged from 0.66 – 0.83 µg/mL) and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with P. watsonii especially with PPWH-7. The study also indicated that P. watsonii extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic P. watsonii was investigated for the first time by bioassay-guided approach. These results demonstrated that P. watsonii selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence, P. watsonii has the potential to be further exploited for the discovery and development of new anti cancer drugs

Nurse-patient interaction and communication: a systematic literature review

Aim: The purpose of this review is to describe the use and definitions of the concepts of nurse-patient interaction and nurse-patient communication in nursing literature. Furthermore, empirical findings of nurse-patient communication research will be presented, and applied theories will be shown. Method: An integrative literature search was executed. The total number of relevant citations found was 97. The search results were reviewed, and key points were extracted in a standardized form. Extracts were then qualitatively summarized according to relevant aspects and categories for the review. Results: The relation of interaction and communication is not clearly defined in nursing literature. Often the terms are used interchangeably or synonymously, and a clear theoretical definition is avoided or rather implicit. Symbolic interactionism and classic sender-receiver models were by far the most referred to models. Compared to the use of theories of adjacent sciences, the use of original nursing theories related to communication is rather infrequent. The articles that try to clarify the relation of both concepts see communication as a special or subtype of interaction. Conclusion: The included citations all conclude that communication skills can be learned to a certain degree. Involvement of patients and their role in communication often is neglected by authors. Considering the mutual nature of communication, patients’ share in conversation should be taken more into consideration than it has been until now. Nursing science has to integrate its own theories of nursing care with theories of communication and interaction from other scientific disciplines like sociology

Impact of inactivity and exercise on the vasculature in humans

The effects of inactivity and exercise training on established and novel cardiovascular risk factors are relatively modest and do not account for the impact of inactivity and exercise on vascular risk. We examine evidence that inactivity and exercise have direct effects on both vasculature function and structure in humans. Physical deconditioning is associated with enhanced vasoconstrictor tone and has profound and rapid effects on arterial remodelling in both large and smaller arteries. Evidence for an effect of deconditioning on vasodilator function is less consistent. Studies of the impact of exercise training suggest that both functional and structural remodelling adaptations occur and that the magnitude and time-course of these changes depends upon training duration and intensity and the vessel beds involved. Inactivity and exercise have direct “vascular deconditioning and conditioning” effects which likely modify cardiovascular risk