Effects of moderate beer consumption on first-line immunity of healthy adults

Moderate alcohol consumption has shown to induce benefits on host specific (cell-mediated and humoral) immune system, but there is scarce literature regarding first-line immune responses. The aim of this study was to investigate differences in non-specific immunity after alcohol abstention and moderate beer consumption in healthy adults. After a 30 day-alcohol abstemious period, 57 healthy volunteers were submitted to a daily moderate consumption of beer (330 mL for women and 660 mL for men, respectively) during the following 30 days. White blood cell counts and phagocytic and oxidative burst activity were evaluated at three points: a) basal, b) abstemious, c) after moderate consumption of beer. Absolute values of leukocytes, neutrophils, lymphocytes and basophiles (x10(9)/L) increased significantly in women from point b to point c (6.34 +/- 1.26 vs. 7.27 +/- 1.97, 3.43 +/- 0.88 vs. 4.13 +/- 1.53, 2.14 +/- 0.50 vs. 2.38 +/- 0.63, and 0.05 +/- 0.02 vs. 0.06 +/- 0.03, respectively; p < 0.05) as well as basophils in men (0.05 +/- 0.03 vs. 0.06 +/- 0.03). A significant increase of oxidative burst capacity was also observed after the moderate consumption of beer in both women (33.90 +/- 19.00 vs. 48.86 +/- 21.83) and men (27.39 +/- 18.13 vs. 39.25 +/- 24.53). In healthy adults, after 30 days of moderate beer consumption the parameter describing the non-specific immunity improved when compared to the basal situation. For several of these parameters, the response is more enhanced in women.     

Encapsulation and exfoliation of inorganic lamellar fillers into polycaprolactone by electrospinning

The present paper reports, for the first time, the successful fabrication of layered double hydroxide (Mg-Al LDH)-reinforced polycaprolactone (PCL) nanofibers by electrospinning. Either the LDH in carbonate form or an LDH organically modified with 12-hydroxydodecanoic acid (LDH-HA) were incorporated into PCL and electrospun using a voltage of 20 KV. The LDH-HA was prepared by an ionic exchange reaction from pristine LDH and encapsulated into PCL from acetone solutions at 15 wt %. The morphological analysis showed pure PCL fibers with an average diameter of 600 +/- 50 nm, and this dimension was maintained in the fibers with LDH, with the inorganic component residing outside the fibers and not exfoliated. At variance, the fibers with the LDH-HA showed a significantly lower average diameter in the range of 350 +/- 50 nm, indicating the improved electrospinnability of PCL. Moreover, the inorganic lamellae were exfoliated, as shown by X-rays and residing inside the nanofibers as demonstrated by energy dispersive X-ray spectroscopy analysis. The structural parameters, such as degradation temperature and crystallinity, were investigated for all the samples and correlated with the electrospinning process.     

Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer

Stemness was recently depicted as a dynamic condition in normal and tumor cells. We found that the embryonic protein Cripto-1 (CR1) was expressed by normal stem cells at the bottom of colonic crypts and by cancer stem cells (CSCs) in colorectal tumor tissues. CR1-positive populations isolated from patient-derived tumor spheroids exhibited increased clonogenic capacity and expression of stem-cell-related genes. CR1 expression in tumor spheroids was variable over time, being subject to a complex regulation of the intracellular, surface and secreted protein, which was related to changes of the clonogenic capacity at the population level. CR1 silencing induced CSC growth arrest in vitro with a concomitant decrease of Src/Akt signaling, while in vivo it inhibited the growth of CSC-derived tumor xenografts and reduced CSC numbers. Importantly, CR1 silencing in established xenografts through an inducible expression system decreased CSC growth in both primary and metastatic tumors, indicating an essential role of CR1 in the regulation the CSC compartment. These results point to CR1 as a novel and dynamically regulated effector of stem cell functions in colorectal cancer.Increasing evidence suggests that stemness is not a static condition, neither in normal cells nor in cancer.^{1, 2} Spontaneous interconversion between states of higher and lower stemness has been observed both in embryonic stem cells (ESCs) and in adult tissues.^{3, 4, 5, 6} In cancer, the transition between stem cells and non-stem cells is critical to the maintenance of a phenotypic equilibrium in which cell populations rapidly regulate relative hierarchic proportions in response to external stimuli.⁷ Stem cell dynamics have been particularly studied in the intestinal epithelium, where recent studies provided impressive insight on the behavior of normal stem cells.⁸ By contrast, the comprehension of stem cells dynamics in colorectal cancer (CRC) is at its beginning, although cancer stem cells (CSC) plasticity has been observed as the result of therapeutic and microenvironmental factors and proposed to influence patient outcome.⁹ In particular, the extracellular cues that regulate stem cell metastability in CRC remain largely unknown. Cripto-1 (CR1), also known as teratocarcinoma-derived growth factor-1 (TDGF-1), is an extracellular glycosylphosphatidylinositol (GPI)-anchored protein expressed in mouse and human ESCs, where it regulates stem cell differentiation.¹⁰ CR1 is usually low or absent in adult tissues but is reactivated in pathological conditions. Indeed, CR1 expression is rapidly induced in skeletal muscle upon acute injury and it is required in the muscle stem cell (satellite cell) compartment to promote efficient tissue regeneration.¹¹ CR1 is also overexpressed in several types of human tumors¹² where it has a functional role in malignant transformation.¹³ Intriguingly, CR1 was found to be expressed in human ESCs with the highest self-renewal potential and was identified as a potential surface marker for an undifferentiated subpopulation in human embryonic carcinoma cells.^{14, 15} We found that CR1 is expressed by cells at the bottom of colonic crypts in normal human and mouse colon and by CSCs in human tumor tissues. In multicellular spheroid cultures of patient-derived colon cancer cells, CR1 expression was subject to a complex regulation at the intracellular, surface and secreted levels, which reflected the amount of self-renewing cells. Furthermore, CR1 silencing decreased CSC numbers and tumor growth, pointing to a functional role of this protein in regulating the size of the CSC compartment.     

Synthesis of novel antimitotic agents based on 2-amino-3-aroyl-5-(hetero)arylethynyl thiophene derivatives

Microtubules are dynamic structures that play a crucial role in cellular division and are recognized as an important target for cancer therapy. In search of new compounds with strong antiproliferative activity and simple molecular structure, a new series of 2-amino-3-(3′,4′,5′-trimethoxybenzoyl)-5-(hetero)aryl ethynyl thiophene derivatives was prepared by the Sonogashira coupling reaction of the corresponding 5-bromothiophenes with several (hetero)aryl acetylenes. When these compounds were analyzed in vitro for their inhibition of cell proliferation, the 2- and 3-thiophenyl acetylene derivatives were the most powerful compounds, both of which exerted cytostatic effects at submicromolar concentrations. In contrast, the presence of a more flexible ethyl chain between the (hetero)aryl and the 5-position of the thiophene ring resulted in significant reduction in activity relative to the 5-(hetero)aryl acetylene substituted derivatives. The effects of a selected series of compounds on cell cycle progression correlated well with their strong antiproliferative activity and inhibition of tubulin polymerization. We found that the antiproliferative effects of the most active compounds were associated with increase of the proportion of cells in the G₂/M and sub-G₁ phases of the cell cycle.     

Antiviral activity of seed extract from Citrus bergamia towards human retroviruses

The effects of an extract from Citrus bergamia (BSext) and those of two products purified from the same extract, that is, nomilin and limonin, and reference compounds, towards HTLV-1 have been reported. Moreover, they were also compared with those obtained towards HIV-1. Results showed that the efficacy of both BSext and limonin in inhibiting HTLV-1 as well as HIV-1 expression in infected cells, as evaluated by comparable quantitative assays, was close to that of the effective, reference compounds, respectively. The protective effect of BSext and of the purified products was associated with the inhibition of both HTLV-1 and HIV-1 RT activities in conceptually similar, cell-free assays. The cytotoxicity of the assayed compounds of natural origin was substantially less pronounced than that of the reference compounds, thus showing a favourable selectivity index for the novel BSext product.     

The agent is right: when motor embodied cognition is space-dependent

The role of embodied mechanisms in processing sentences endowed with a first person perspective is now widely accepted. However, whether embodied sentence processing within a third person perspective would also have motor behavioral significance remains unknown. Here, we developed a novel version of the Action-sentence Compatibility Effect (ACE) in which participants were asked to perform a movement compatible or not with the direction embedded in a sentence having a first person (Experiment 1: You gave a pizza to Louis) or third person perspective (Experiment 2: Lea gave a pizza to Louis). Results indicate that shifting perspective from first to third person was sufficient to prevent motor embodied mechanisms, abolishing the ACE. Critically, ACE was restored in Experiment 3 by adding a virtual "body" that allowed participants to know "where" to put themselves in space when taking the third person perspective, thus demonstrating that motor embodied processes are space-dependent. A fourth, control experiment, by dissociating motor response from the transfer verb's direction, supported the conclusion that perspective-taking may induce significant ACE only when coupled with the adequate sentence-response mapping.     

DNA electrophoretic migration patterns change after exposure of Jurkat cells to a single intense nanosecond electric pulse

Intense nanosecond pulsed electric fields (nsPEFs) interact with cellular membranes and intracellular structures. Investigating how cells respond to nanosecond pulses is essential for a) development of biomedical applications of nsPEFs, including cancer therapy, and b) better understanding of the mechanisms underlying such bioelectrical effects. In this work, we explored relatively mild exposure conditions to provide insight into weak, reversible effects, laying a foundation for a better understanding of the interaction mechanisms and kinetics underlying nsPEF bio-effects. In particular, we report changes in the nucleus of Jurkat cells (human lymphoblastoid T cells) exposed to single pulses of 60 ns duration and 1.0, 1.5 and 2.5 MV/m amplitudes, which do not affect cell growth and viability. A dose-dependent reduction in alkaline comet-assayed DNA migration is observed immediately after nsPEF exposure, accompanied by permeabilization of the plasma membrane (YO-PRO-1 uptake). Comet assay profiles return to normal within 60 minutes after pulse delivery at the highest pulse amplitude tested, indicating that our exposure protocol affects the nucleus, modifying DNA electrophoretic migration patterns.     

<Emphasis Type="Italic">N</Emphasis>-Arylpiperazine modified analogues of the P2X<Subscript>7</Subscript> receptor KN-62 antagonist are potent inducers of apoptosis of human primary osteoclasts

Summary The P2X₇ nucleotide receptor is an ATP-gated ion channel that plays an important role in bone cell function. Here, we investigated the effects of L-tyrosine derivatives 1–3 as potent P2X₇ antagonists on human primary osteoclasts. We found that the level of expression of P2X₇ receptor increased after treatment with the derivatives 1–3, together with the induction of high levels of apoptosis. This effect is associated with activation of caspase-3 and inhibition of expression of IL-6. Interestingly, no pro-apoptotic effect of compounds 1–3 was found on human osteoblasts. Our results suggest that the development of specific P2X₇ receptor antagonists may be considered a useful tool to modulate apoptosis of human osteoclasts. Since bone loss due to osteoclast-mediated resorption represents one of the major unsolved problem in osteopenic disorders, the identification of molecules able to induce apoptosis of osteoclasts is of great interest for the development of novel therapeutic strategies.