Influence of Polydatin on the Tumor Microenvironment In Vitro: Studies with a Colon Cancer Cell Model

The tumor microenvironment of colon carcinoma, the site at which tumor cells and the host immune system interact, is influenced by signals from tumor cells, immunocompetent cells, and bacterial components, including LPS. A large amount of LPS is available in the colon, and this could promote inflammation and metastasis by enhancing tumor cell adhesion to the endothelium. Polydatin (PD), the 3-β-D-glucoside of trans-resveratrol, is a polyphenol with anti-cancer, anti-inflammatory, and immunoregulatory effects. This study was designed to explore whether PD is able to produce antiproliferative effects on three colon cancer lines, to reduce the expression of adhesion molecules that are upregulated by LPS on endothelial cells, and to decrease the proinflammatory cytokines released in culture supernatants. Actually, we investigated the effects of PD on tumor growth in a coculture model with human mononuclear cells (MNCs) that mimics, at least in part, an in vitro tumor microenvironment. The results showed that PD alone or in combination with MNC exerts antiproliferative and proapoptotic effects on cancer cells, inhibits the production of the immunosuppressive cytokine IL-10 and of the proinflammatory cytokines upregulated by LPS, and reduces E-selectin and VCAM-1 on endothelial cells. These data provide preclinical support to the hypothesis that PD could be of potential benefit as a therapeutic adjuvant in colon cancer treatment and prevention.     

Sperm Physiological Response to Female Serum—Potential New Insights into the Reproductive Incompatibility Diagnostics

Infertility is assumed to arise exclusively from male- and female-dependent pathological factors. However, recent studies have indicated that reproductive failure may also result from the reproductive incompatibility of the partners. Selection against such incompatibilities likely occurs via female-derived reproductive secretions, including follicular fluid (FF), that mediate gamete-level mate choice towards the sperm of specific males. To facilitate potential development of diagnostic tests for human reproductive incompatibility, we examined whether sperm physiological response to female serum indicate male–female compatibility in the presence of FF. We performed a full-factorial experiment, in which the sperm of 10 males were treated with the FF and serum of 6 healthy females. We found that sperm motility and viability in both biofluids were highly similar and that in 70% of the males, sperm serum treatment predicted male–female compatibility. We also identified male human leucocyte antigen (HLA) alleles and female (FF and serum) anti-HLA antibodies and tested whether the number of allele–antibody matches predict sperm physiological response to female fluids. However, no association was found between measured sperm traits and the number of allele–antibody matches. Overall, the present results may open novel possibilities for the future development of reproductive incompatibility tests and may pave the way towards more accurate infertility diagnostics and treatments.     

Changes in Radiosensitivity to Gamma-Rays of Lymphocytes from Hyperthyroid Patients Treated with I-131

This study investigated the peripheral blood lymphocytes (PBL) response to a dose of γ-rays in patients treated with radioiodine (I-131) for hyperthyroidism vs. healthy controls, to gain information about the individual lymphocytes’ radio-sensitivity. Blood samples were taken from 18 patients and 10 healthy donors. Phosphorylated histone variant H2AX (γ-H2AX) and micronuclei (MN) induction were used to determine the change in PBL radio-sensitivity and the correlations between the two types of damage. The two assays showed large inter-individual variability in PBL background damage and in radio-sensitivity (patients vs. healthy donors). In particular, they showed an increased radio-sensitivity in 36% and 33% of patients, decrease in 36% and 44%, respectively. There was a scarce correlation between the two assays and no dependence on age or gender. A significant association was found between high radio-sensitivity conditions and induced hypothyroidism. PBL radio-sensitivity in the patient group was not significantly affected by treatment with I-131, whereas there were significant changes inter-individually. The association found between clinical response and PBL radio-sensitivity suggests that the latter could be used in view of the development of personalized treatments.     

Functional Heterodimerization between the G Protein-Coupled Receptor GPR17 and the Chemokine Receptors 2 and 4: New Evidence

GPR17, a G protein-coupled receptor, is a pivotal regulator of myelination. Its endogenous ligands trigger receptor desensitization and downregulation allowing oligodendrocyte terminal maturation. In addition to its endogenous agonists, GPR17 could be promiscuously activated by pro-inflammatory oxysterols and chemokines released at demyelinating lesions. Herein, the chemokine receptors CXCR2 and CXCR4 were selected to perform both in silico modelling and in vitro experiments to establish their structural and functional interactions with GPR17. The relative propensity of GPR17 and CXCR2 or CXCR4 to form homo- and hetero-dimers was assessed by homology modelling and molecular dynamics (MD) simulations, and co-immunoprecipitation and immunoenzymatic assay. The interaction between chemokine receptors and GPR17 was investigated by determining receptor-mediated modulation of intracellular cyclic adenosine monophosphate (cAMP). Our data show the GPR17 association with CXCR2 or CXCR4 and the negative regulation of these interactions by CXCR agonists or antagonists. Moreover, GPR17 and CXCR2 heterodimers can functionally influence each other. In contrast, CXCR4 can influence GPR17 functionality, but not vice versa. According to MD simulations, all the dimers reached conformational stability and negative formation energy, confirming the experimental observations. The cross-talk between these receptors could play a role in the development of the neuroinflammatory milieu associated with demyelinating events.     

A hierarchical optimization technique for the strategic design of distribution networks

The paper addresses the optimal design of the last supply chain branch, i.e., the Distribution Network (DN), starting from manufacturers till the retailers. It considers a distributed system composed of different stages connected by material links labeled with suitable performance indices. A hierarchical procedure employing direct graph (digraph) modeling, mixed integer linear programming, and the Analytic Hierarchy Process (AHP) is presented to select the optimal DN configuration. More in detail, a first-level DN optimization problem taking into account the definition and evaluation of the distribution chain performance provides a set of Pareto optimal solutions defined by digraph modeling. A second level DN optimization using the AHP method selects, on the basis of further criteria, the DN configuration from the Pareto face alternatives. To show the method effectiveness, the optimization model is applied to a case study describing an Italian regional healthcare drug DN. The problem solution by the proposed design method allows improving the DN flexibility and performance.     

How probiotics face food stress: They get by with a little help

Abstract

The dietary consumption of probiotics in the form of pharmaceuticals or functional food can improve human health and contribute to disease prevention. However, the biological activity and health potential of food-delivered probiotics can be severely compromised by the stress conditions encountered by the microorganisms throughout the manufacture process, from probiotic preparation to their inclusion into food, subsequent storage and ingestion. Here, we give an account of the stress factors that can have major negative impacts on probiotic viability and functionality, with a focus on food-related environmental adverse conditions. We also describe some of the mechanisms elicited by the microbial cells to counteract these stresses and summarize a few relevant approaches proposed in literature to develop more robust and competitive probiotics by enhancing their stress tolerance, with the aim to improve the efficacy and health value of probiotic functional food.     

Behaviour of oat globulins in lactic acid fermentation of oat bran

Oat bran fermentation (OBF) is used to produce non-dairy yogurt-type products. Such products may be designed being rich in probiotic bacteria and/or dietary-fibre. Oat bran is, however, also rich in proteins, especially 12 S globulins. Understanding the behaviour of globulins in OBF would thus offer a basis for further exploitation of proteins in the product design. The behaviour of oat globulins was monitored during a model OBF in order to study changes in protein solubility and possible protein hydrolysis. Proteins were extracted from OBF samples with a buffered and a non-buffered extraction procedure. The extracts were analyzed with SDS-PAGE and a Lowry assay. Combined effect of pH and NaCl-concentration on the solubility of oat globulin isolate was studied. The solubility of oat globulins decreased during OBF; this appeared as their shift from the salt-soluble fraction to the residual protein fraction. The shift in oat globulin solubility was due to the acidifying conditions present in OBF, which lead to the unfolding of globulins and also apparently induced protein aggregation. No major protein hydrolysis was observed during OBF.     

Photoproduction of H2 by wildtype Anabaena PCC 7120 and a hydrogen uptake deficient mutant: from laboratory experiments to outdoor culture

We have analyzed the filamentous cyanobacterium Anabaena PCC 7120 (wildtype) containing one nitrogenase, one uptake hydrogenase and one bidirectional hydrogenase and its hydrogen uptake deficient mutant AMC 414 for their H₂ production capacities. Anabaena PCC 7120 and AMC 414 had similar growth rates in turbidostat mode with increased growth rates at higher light intensity. Rates of C₂H₂ reduction were similar for both strains. In contrast to the wildtype, AMC 414 produced H₂ in a PhotoBioReactor (PhBR) using air as the lifting gas. The rate of H₂ production increased with light intensity and was not even saturated at 456 μEm⁻² s⁻¹. H₂ production increased significantly when replacing the air with argon. The maximal H₂ production during outdoor conditions was recorded using AMC 414 with a peak at 14.9 ml H₂ h⁻¹ l⁻¹. Despite the relatively high production, maximal efficiency of solar energy to H₂ conversion was only 0.042%. A molecular method was developed to analyze the relative abundancies of weight and mutant in competition experiments in the PhBR.     

Overt and covert identification of fragmented objects inferred from performance and electrophysiological measures.

The authors investigated visual processing leading to object identification by manipulating the number of fragments and nature of the study. During the study, participants either named or drew objects in Experiment 1 and drew them all in Experiment 2. During the test, participants made an identification judgment at each of 6 different fragmentation levels for studied and new objects. Fewer fragments were needed to identify studied than unstudied objects. Reaction times (RTs) were faster for studied than unstudied objects both at identification and at the preceding level. Event-related brain potentials (ERPs) to unidentified objects were characterized by a late negativity in contrast to a positivity to identified objects. ERPs to studied but not to new objects contained a smaller and later version of the identification positivity at level just prior to identification, which was not due to differential response confidence. Much covert visual analysis and even object identification may precede overt identification, depending on the nature of prior experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)