The therapeutic aspects of the endocannabinoid system (ECS) for cancer and their development: from nature to laboratory

The endocannabinoid system (ECS) is a group of neuromodulatory lipids and their receptors, which are widely distributed in mammalian tissues. ECS regulates various cardiovascular, nervous, and immune system functions inside cells. In recent years, there has been a growing body of evidence for the use of synthetic and natural cannabinoids as potential anticancer agents. For instance, the CB1 and CB2 receptors are assumed to play an important role inside the endocannabinoid system. These receptors are abundantly expressed in the brain and fatty tissue of the human body. Despite recent developments in molecular biology, there is still a lack of knowledge about the distribution of CB1 and CB2 receptors in the human kidney and their role in kidney cancer. To address this gap, we explore and demonstrate the role of the endocannabinoid system in renal cell carcinoma (RCC). In this brief overview, we elucidate the therapeutic aspects of the endocannabinoid system for various cancers and explain how this system can be used for treating kidney cancer. Overall, this review provides new insights into cannabinoids' mechanisms of action in both in vivo and in vitro models, and focuses on recent discoveries in the field

The Darboux-Backlund transformation for the static 2-dimensional continuum Heisenberg chain

We construct the Darboux-Backlund transformation for the sigma model describing static configurations of the 2-dimensional classical continuum Heisenberg chain. The transformation is characterized by a non-trivial normalization matrix depending on the background solution. In order to obtain the transformation we use a new, more general, spectral problem.Comment: 12 page

Interleukin 1-β, Interleukin-1 Receptor Antagonist, and Interleukin 18 in Children with Acute Spontaneous Urticaria

Very little is known about the role of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in urticaria. Material and Methods. Serum levels of IL-1β, IL-1 receptor antagonist (IL-1RA), and IL-18 were measured in 56 children with urticaria and in 41 healthy subjects. Results. Serum IL-1β did not differ between children with acute urticaria and controls. Children with single episode of urticaria had higher levels of IL-1RA and IL-18 than healthy subjects. In children with single episode of urticaria, level of IL-1RA correlated with C-reactive protein (CRP), D-dimer, and IL-1β levels. In subjects with recurrence of urticaria IL-1RA was positively correlated with WBC and D-dimer levels. No correlation of cytokine levels and urticaria severity scores (UAS) in all children with urticaria was observed. In children with single episode of urticaria UAS correlated with CRP level. In the group with single episode of urticaria and in children with symptoms of upper respiratory infection, IL-1RA and IL-18 levels were higher than in controls. The former was higher than in noninfected children with urticaria. In conclusion, this preliminary study documents that serum IL-1RA and IL-18 levels are increased in some children with acute urticaria. However further studies are necessary to define a pathogenic role of IL-1β, IL-1RA, and IL-18 in urticaria

Impact of minority concentration on fundamental (H)D ICRF heating performance in JET-ILW

ITER will start its operation with non-activated hydrogen and helium plasmas at a reduced magnetic field of B-0 = 2.65 T. In hydrogen plasmas, the two ion cyclotron resonance frequency (ICRF) heating schemes available for central plasma heating (fundamental H majority and 2nd harmonic He-3 minority ICRF heating) are likely to suffer from relatively low RF wave absorption, as suggested by numerical modelling and confirmed by previous JET experiments conducted in conditions similar to those expected in ITER's initial phase. With He-4 plasmas, the commonly adopted fundamental H minority heating scheme will be used and its performance is expected to be much better. However, one important question that remains to be answered is whether increased levels of hydrogen (due to e. g. H pellet injection) jeopardize the high performance usually observed with this heating scheme, in particular in a full-metal environment. Recent JET experiments performed with the ITER-likewall shed some light onto this question and the main results concerning ICRF heating performance in L-mode discharges are summarized here

Cross-sensitization to Artemisia and Ambrosia Pollen Allergens in an Area Located Outside of the Current Distribution Range of Ambrosia

Introduction : The role of long-distance transported (LDT) Ambrosia pollen in inducing new sensitization and affecting sensitization rates in Artemisia -sensitized patients is unclear. Aim : The aim of this study was to estimate the degree of cross-sensitization to Ambrosia / Artemisia allergens in citizens of Poznan (Western Poland). This area is covered by extensive Artemisia populations but does not currently have local Ambrosia populations. Material and methods : Sera of 119 patients were tested by fluoroenzyme immunoassay (CAP-FEIA system) against pollen allergen extracts of Artemisia vulgaris and Ambrosia artemisiifolia , an allergenic component of A. vulgaris (nArt v 1), and an allergenic component of A. artemisiifolia ( nAmb a 1 ). Skin prick tests (SPTs, n = 86) were performed with pollen allergen extracts of A. vulgaris and A. artemisiifolia . Artemisia and Ambrosia pollen in ambient air was collected (1996�2013) by a Hirst type volumetric trap sited at roof level (33 m). Results : The SPT showed that the prevalence of sensitization to Ambrosia and Artemisia pollen exceeded 3.5, and 10.5, respectively. The measurements of IgE in blood serum (CAP-FEIA) revealed that among Ambrosia -sensitized patients 90.1 (20/22 patients) were concomitantly sensitized to Artemisia . 59.1 (13/22) of these patients reacted to nArt v 1, suggesting primary sensitization to Artemisia pollen. Only 2 (9.1) patients were mono-sensitized to Ambrosia pollen extract, but surprisingly not to nAmb a 1 . Conclusions : The LDT Ambrosia pollen had a negligible effect on the rate of sensitization to Ambrosia allergens in Poznan and did not increase the prevalence of sensitization to Artemisia pollen in this region. However, the majority of patients showing hypersensitization to Artemisia pollen might also present symptoms during elevated episodes of LDT of Ambrosia pollen

Minority and mode conversion heating in (3He)-H JET plasma

Radio frequency (RF) heating experiments have recently been conducted in JET (He-3)-H plasmas. This type of plasmas will be used in ITER's non-activated operation phase. Whereas a companion paper in this same PPCF issue will discuss the RF heating scenario's at half the nominal magnetic field, this paper documents the heating performance in (He-3)-H plasmas at full field, with fundamental cyclotron heating of He-3 as the only possible ion heating scheme in view of the foreseen ITER antenna frequency bandwidth. Dominant electron heating with global heating efficiencies between 30% and 70% depending on the He-3 concentration were observed and mode conversion (MC) heating proved to be as efficient as He-3 minority heating. The unwanted presence of both He-4 and D in the discharges gave rise to 2 MC layers rather than a single one. This together with the fact that the location of the high-field side fast wave (FW) cutoff is a sensitive function of the parallel wave number and that one of the locations of the wave confluences critically depends on the He-3 concentration made the interpretation of the results, although more complex, very interesting: three regimes could be distinguished as a function of X[He-3]: (i) a regime at low concentration (X[He-3] < 1.8%) at which ion cyclotron resonance frequency (ICRF) heating is efficient, (ii) a regime at intermediate concentrations (1.8 < X[He-3] < 5%) in which the RF performance is degrading and ultimately becoming very poor, and finally (iii) a good heating regime at He-3 concentrations beyond 6%. In this latter regime, the heating efficiency did not critically depend on the actual concentration while at lower concentrations (X[He-3] < 4%) a bigger excursion in heating efficiency is observed and the estimates differ somewhat from shot to shot, also depending on whether local or global signals are chosen for the analysis. The different dynamics at the various concentrations can be traced back to the presence of 2 MC layers and their associated FW cutoffs residing inside the plasma at low He-3 concentration. One of these layers is approaching and crossing the low-field side plasma edge when 1.8 < X[He-3] < 5%. Adopting a minimization procedure to correlate the MC positions with the plasma composition reveals that the different behaviors observed are due to contamination of the plasma. Wave modeling not only supports this interpretation but also shows that moderate concentrations of D-like species significantly alter the overall wave behavior in He-3-H plasmas. Whereas numerical modeling yields quantitative information on the heating efficiency, analytical work gives a good description of the dominant underlying wave interaction physics

Treatment goal attainment for secondary prevention in coronary patients with or without diabetes mellitus : Polish multicenter study POLASPIRE

Introduction: Cardiovascular disease is still a leading cause of death in Poland and across Europe. The aim of this study was to assess the attainment of the main treatment goals for secondary cardiovascular prevention in coronary patients with or without diabetes mellitus (DM) in Poland. Material and methods: The study group included 1026 patients (65.5 ±9 y.o.; males: 72%) included at least 6 months after the index hospitalisation for myocardial infarction, unstable angina, elective percutaneous coronary intervention or coronary artery bypass surgery. The target and treatment goals were defined according to the 2016 European Society of Cardiology guidelines on cardiovascular prevention. Results: Patients with DM (n = 332; 32%) were slightly older compared to non-diabetic (n = 694) individuals (67.2 ±7 vs. 64.6 ±9 years old; p < 0.0001). The DM goal was achieved in 196 patients (60%). The rate of primary (LDL: 51% vs. 35%; p < 0.0001) and secondary (non-HDL: 56% vs. 48%; p < 0.02) goal attainment was higher in DM(+) compared to DM(–) patients. The rate of target blood pressure was lower in DM(+) than in normoglycemic patients (52% vs. 61% at < 140/90 mm Hg, p < 0.01. As expected, goal achievement of normal weight (9.5% vs. 19%; p < 0.0001) and waist circumference (7% vs. 15%; p < 0.001) was lower in diabetic patients and the rate of regular physical activity was similar (DM+ 12% vs. DM– 14%; p = ns). Finally, there was no difference in active smokers (DM+ 23% vs. DM– 22%; p = ns). Conclusions: Great majority of Polish patients in secondary prevention do not achieve treatment goals. Although lipid goals attainment is better in DM and the rate of smokers is similar, the management of all risk factors needs to be improved

Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis

Background: Sympathetic tone is one of the main determinants of blood pressure (BP) variability and treatment-resistant hypertension. The aim of our study was to assess changes in BP variability after renal denervation (RDN). In addition, on an exploratory basis, we investigated whether baseline BP variability predicted the BP changes after RDN. Methods: We analyzed 24-h BP recordings obtained at baseline and 6 months after RDN in 167 treatmentresistant hypertension patients (40% women; age, 56.7 years; mean 24-h BP, 152/90 mmHg) recruited at 11 expert centers. BP variability was assessed by weighted SD [SD over time weighted for the time interval between consecutive readings (SDiw)], average real variability (ARV), coefficient of variation, and variability independent of the mean (VIM). Results: Mean office and 24-h BP fell by 15.4/6.6 and 5.5/ 3.7 mmHg, respectively (P &lt; 0.001). In multivariable-adjusted analyses, systolic/diastolic SDiw and VIM for 24-h SBP/DBP decreased by 1.18/0.63 mmHg (P 0.01) and 0.86/0.42 mmHg (P 0.05), respectively, whereas no significant changes in ARV or coefficient of variation occurred. Furthermore, baseline SDiw (P ¼ 0.0006), ARV (P ¼ 0.01), and VIM (P ¼ 0.04) predicted the decrease in 24-h DBP but not 24-h SBP after RDN. Conclusion: RDN was associated with a decrease in BP variability independent of the BP level, suggesting that responders may derive benefits from the reduction in BP variability as well. Furthermore, baseline DBP variability estimates significantly correlated with mean DBP decrease after RDN. If confirmed in younger patients with less arterial damage, in the absence of the confounding effect of drugs and drug adherence, baseline BP variability may prove a good predictor of BP response to RDN

Mathematical images in advertising: constructing difference and shaping identity, in global consumer culture

Mathematics educators have long emphasised the importance of attitudes and feelings towards mathematics, as crucial in motivating (or not) its learning and use, and as influenced in turn by its social images. This paper is about images of mathematics. Our search for advertisements containing such images of in UK daily newspapers, during 2006-2008, found that 4.7% of editions included a ‘mathematical’ advert, compared with 1.7% in pilot work for 1994-2003. The incidence varied across type of newspaper, being correlated with class and gender profiles of the readership. Three-quarters of advertisements were classified as containing only very simple mathematics. ‘Semiotic-discursive’ analysis of selected advertisements suggests that they draw on mathematics not to inform, but to connote qualities like precision, certainty and authority. We discuss the discourse on mathematics in advertising as ‘quasi-pedagogic’ discourse, and argue that its oversimplified forms, being empty of mathematical content, become powerful means for regulating and ‘pedagogising’ today’s global consumers

Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in mucoepidermoid carcinoma cells.

Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Exposure to increasing concentrations of H2O2 resulted in a reduction of cell viability, DNA damage, and early apoptotic phenomena. Hsp60, p-C3, p53, and p21 were assessed by Western blotting and immunocytochemistry before and after OS. Hsp60 and p-C3 were present before and after OS induction. Immunoprecipitation experiments showed an Hsp60/p-C3 complex before OS that persisted after it, while an Hsp60/p53 complex was not detected in either condition. The presence of wild type (wt) p53 was confirmed by RT-PCR, and p21 detection suggested p53 activation after OS. We postulate that, although OS may induce early apoptosis in NCI-H292 cells, Hsp60 exerts an anti-apoptotic effect in these cells and, by extension, it may do so in other cancer cell