Eastern dimension of the ENP – a new challenge for the European Union. The case of Ukraine

У своїй статті автори досліджують суть поняття Європейська політика сусідства (ЄПС), як інструменту розвитку держави в і поза об'єднанням "Європейський Союз". ЄПС розглянутий як "справжній парадокс", що є перехідним, але не обов'язковим чинником для повноправної асоціації в ЄС. Приведені приклади країн ЦВЄ на шляху до європейської інтеграції, зокрема, Польщі, і обкреслені перспективи в рамках ЄПС для України.В своей статье авторы исследуют сущность понятия Европейская политика соседства (ЕПС), как инструмента развития государства в и вне объединения "Европейский Союз". ЕПС рассмотрен как "настоящий парадокс", являющийся переходным, но не обязательным фактором для полноправной ассоциации в ЕС. Приведены примеры стран ЦВЕ на пути к европейской интеграции, в частности, Польши, и очерчены перспективы в рамках ЕПС для Украины

Mimicking of glutathione peroxidase deficiency by exposition of JAR cells to increased level of synthetic hydroperoxide

A short chain synthetic analogue of lipid hydroperoxides was used to overload glutathione peroxidase (GPx) in human choriocarcinoma cell line JAR cells. Cells exposed to 100 µM tBuOOH displayed a 40% reduction in ATP level and significantly increased in membrane permeability, visualised by the lactate dehydrogenase (LDH) release into the extracellular medium. The intracellular level of oxygen free radicals measured as an oxidation of the dichlorodihydro-fluorescein diacetate (H2DCF-DA) significantly increased after 2 hours of cell exposition to 100 µM tBuOOH. Concomitantly MDA, 4-HNE level increased to 2 nmol/mg of cell protein after 2 hours. Mitochondria stained with MitoTracker Red CMXRos displayed a filamentous appearance in control cells but changed into granular less energised organelles after exposition to tBuOOH. Collectively, the above results indicate the importance of the contribution of oxidative stress in the development of pre-eclampsia

Using a smartphone application to promote healthy dietary behaviours and local food consumption

Smartphone “apps” are a powerful tool for public health promotion, but unidimensional interventions have been ineffective at sustaining behavioural change. Various logistical issues exist in successful app development for health intervention programs and for sustaining behavioural change. This study reports on a smartphone application and messaging service, called “SmartAPPetite,” which uses validated behaviour change techniques and a behavioural economic approach to “nudge” users into healthy dietary behaviours. To help gauge participation in and influence of the program, data were collected using an upfront food survey, message uptake tracking, experience sampling interviews, and a follow-up survey. Logistical and content-based issues in the deployment of the messaging service were subsequently addressed to strengthen the effectiveness of the app in changing dietary behaviours. Challenges included creating relevant food goal categories for participants, providing messaging appropriate to self-reported food literacy and ensuring continued participation in the program. SmartAPPetite was effective at creating a sense of improved awareness and consumption of healthy foods, as well as drawing people to local food vendors with greater frequency. This work serves as a storehouse of methods and best practices for multidimensional local food-based smartphone interventions aimed at improving the “triple bottom line” of health, economy, and environment

Synthesis and in vitro antiproliferative activity of novel (4-chloro- and 4-acyloxy-2-butynyl)thioquinolines

The series of new acetylenic thioquinolines containing propargyl, 4-chloro-2-butynyl, and 4-acyloxy-2-butynyl groups have been prepared and tested for antiproliferative activity in vitro against human [SW707 (colorectal adenocarcinoma), CCRF/CEM (leukemia), T47D (breast cancer)] and murine [P388 (leukemia), B16 (melanoma)] cancer lines. Most of the obtained compounds exhibited antiproliferative activity, especially compounds 8, 12, and 21 showed the ID50 values ranging from 0.4 to 3.8 μg/ml comparable to that of cisplatin used as reference compounds

1-methylnicotinamide and its structural analog 1,4-dimethylpyridine for the prevention of cancer metastasis

Background: 1-methylnicotinamide (1-MNA), an endogenous metabolite of nicotinamide, has recently gained interest due to its anti-inflammatory and anti-thrombotic activities linked to the COX-2/PGI2 pathway. Given the previously reported anti-metastatic activity of prostacyclin (PGI2), we aimed to assess the effects of 1-MNA and its structurally related analog, 1,4-dimethylpyridine (1,4-DMP), in the prevention of cancer metastasis. Methods: All the studies on the anti-tumor and anti-metastatic activity of 1-MNA and 1,4-DMP were conducted using the model of murine mammary gland cancer (4T1) transplanted either orthotopically or intravenously into female BALB/c mouse. Additionally, the effect of the investigated molecules on cancer cell-induced angiogenesis was estimated using the matrigel plug assay utilizing 4T1 cells as a source of pro-angiogenic factors. Results: Neither 1-MNA nor 1,4-DMP, when given in a monotherapy of metastatic cancer, influenced the growth of 4T1 primary tumors transplanted orthotopically; however, both compounds tended to inhibit 4T1 metastases formation in lungs of mice that were orthotopically or intravenously inoculated with 4T1 or 4T1-luc2-tdTomato cells, respectively. Additionally, while 1-MNA enhanced tumor vasculature formation and markedly increased PGI2 generation, 1,4-DMP did not have such an effect. The anti-metastatic activity of 1-MNA and 1,4-DMP was further confirmed when both agents were applied with a cytostatic drug in a combined treatment of 4T1 murine mammary gland cancer what resulted in up to 80 % diminution of lung metastases formation. Conclusions: The results of the studies presented below indicate that 1-MNA and its structural analog 1,4-DMP prevent metastasis and might be beneficially implemented into the treatment of metastatic breast cancer to ensure a comprehensive strategy of metastasis control

p53 Activation following Rift Valley Fever Virus Infection Contributes to Cell Death and Viral Production

Rift Valley fever virus (RVFV) is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production

p53 Regulates Cell Cycle and MicroRNAs to Promote Differentiation of Human Embryonic Stem Cells

Multiple studies show that tumor suppressor p53 is a barrier to dedifferentiation; whether this is strictly due to repression of proliferation remains a subject of debate. Here, we show that p53 plays an active role in promoting differentiation of human embryonic stem cells (hESCs) and opposing self-renewal by regulation of specific target genes and microRNAs. In contrast to mouse embryonic stem cells, p53 in hESCs is maintained at low levels in the nucleus, albeit in a deacetylated, inactive state. In response to retinoic acid, CBP/p300 acetylates p53 at lysine 373, which leads to dissociation from E3-ubiquitin ligases HDM2 and TRIM24. Stabilized p53 binds CDKN1A to establish a G1 phase of cell cycle without activation of cell death pathways. In parallel, p53 activates expression of miR-34a and miR-145, which in turn repress stem cell factors OCT4, KLF4, LIN28A, and SOX2 and prevent backsliding to pluripotency. Induction of p53 levels is a key step: RNA-interference-mediated knockdown of p53 delays differentiation, whereas depletion of negative regulators of p53 or ectopic expression of p53 yields spontaneous differentiation of hESCs, independently of retinoic acid. Ectopic expression of p53R175H, a mutated form of p53 that does not bind DNA or regulate transcription, failed to induce differentiation. These studies underscore the importance of a p53-regulated network in determining the human stem cell state