Anticonvulsant valproic acid and other short-chain fatty acids as novel anticancer therapeutics: Possibilities and challenges

Results from numerous pre-clinical studies suggest that a well known anticonvulsant drug valproic acid (VPA) and other short-chain fatty acids (SCFAs) cause significant inhibition of cancer cell proliferation by modulating multiple signaling pathways. First of all, they act as histone deacetylase (HDAC) inhibitors (HDIs), being involved in the epigenetic regulation of gene expression. Afterward, VPA is shown to induce apoptosis and cell differentiation, as well as regulate Notch signaling. Moreover, it up-regulates the expression of certain G protein-coupled receptors (GPCRs), which are involved in various signaling pathways associated with cancer. As a consequence, some pre-clinical and clinical trials were carried out to estimate anticancer effectiveness of VPA, in monotherapy and in new drug combinations, while other SCFAs were tested in pre-clinical studies. The present manuscript summarizes the most important information from the literature about their potent anticancer activities to show some future perspectives related to epigenetic therapy

Use of the far infrared spectroscopy for NaCl and KCl minerals characterization : a case study of halides from Kłodawa in Poland

The paper presents research on chloride minerals of natural origin from Kłodawa (Poland), i.e., colorless, blue and purple halite as well as colorless sylvite. Selected samples of minerals were studied by chemical analysis (ICP-OES, ICP-MS, titration methods) and crystallographic measurements. Then, for the tested halides, research was carried out using far-infrared spectroscopy. Spectroscopic studies confirmed the simple way of distinguishing NaCl and KCl minerals using far-infrared spectroscopy, known in the literature. The novelty is that the article presents for the first time the experimental far infrared spectra of natural blue and purple halite. It was observed that the blue (178 cm−1) and purple (176 cm−1) halites have the strongest infrared band slightly shifted towards higher wavenumbers compared to colorless halite (174 cm−1). As part of the work, the infrared spectra of the crystal structure models of sodium and potassium chloride were calculated for the first time using the density functional theory (with the B3LYP functional and the 6-31G* basis set, 125-atom model). The proposed approach can be used not only as a powerful method differentiating NaCl and KCl minerals, but it can also help with understanding of different defects in crystal lattices for naturally occurring halides and crystals of other minerals

The chemistry and quality of water from the artesian wells of the Jurassic aquifer in Krakow

Selected quality parameters of groundwater from four artesian wells of the Jurassic aquifer located in the center of Krakow (Cracow) are presented. Water from these public wells i.e. Nadzieja, Jagielloński, Królewski and Lajkonik, during 20 years of exploitation, has had constant bacteriological purity and rather constant chemical composition. A comparison of nitrates concentration in the investigated wells with Quaternary wells located in the same area, and with municipal drinking water in Krakow shows that water from the above-mentioned four wells is characterized by the lowest concentration of NO3−  ions. Very low nitrate and nitrite concentration suggests that despite passage of time the chemical composition of water from the investigated intakes is not affected by anthropogenic pollution because of isolation of water reservoir due to geological conditions

Usefulness of kidney function evaluation in the interpretation of cardiovascular risk in the group of patients with arterial hypertension

Wstęp Przewlekła choroba nerek jest niezależnym czynnikiem ryzyka chorób układu sercowo-naczyniowego (CVD). Również nadciśnienie tętnicze jest czynnikiem ryzyka CVD i występuje u 70-85% pacjentów z przewlekłą chorobą nerek. W obecnych wytycznych Kidney Disease Outcomes Quality Initiative zaleca się, by funkcję nerek oceniać poprzez oszacowanie przesączania kłębuszkowego (GFR) zamiast stężenia kreatyniny w surowicy. Pozwala to na zidentyfikowanie pacjentów z przewlekłą chorobą nerek oraz ocenę stopnia niewydolności nerek. Materiał i metody Oceniano częstość występowania upośledzonej funkcji nerek na podstawie GFR u 58 hospitalizowanych osób (20 kobiet oraz 38 mężczyzn) chorujących na nadciśnienie tętnicze. Pacjentów podzielono na dwie grupy: A - 28 osób bez towarzyszącej choroby niedokrwiennej serca (9 kobiet i 19 mężczyzn) oraz B - 30 osób ze stwierdzoną chorobą niedokrwienną serca (11 kobiet i 19 mężczyzn). Wyniki Zgodnie ze wzorem Modification of Diet in Renal Disease stwierdzono: 1. stopień przewlekłej choroby nerek w grupie pacjentów z nadciśnieniem tętniczym bez towarzyszącej choroby niedokrwiennej serca (A) u 25% osób, natomiast w grupie pacjentów chorujących na nadciśnienie tętnicze i chorobę niedokrwienną serca (B) u 6,67% chorych; 2. stopień przewlekłej choroby nerek w grupie pacjentów z nadciśnieniem tętniczym bez towarzyszącej choroby niedokrwiennej serca (A) u 39,29% osób, natomiast w grupie pacjentów z nadciśnieniem tętniczym i chorobą niedokrwienną serca (B) u 50% chorych; 3. stopień przewlekłej choroby nerek w grupie pacjentów z nadciśnieniem tętniczym bez towarzyszącej choroby niedokrwiennej serca (A) u 14,29% osób, natomiast w grupie pacjentów z nadciśnieniem tętniczym i chorobą niedokrwienną serca (B) u 23,33% osób. Wnioski Pacjenci z nadciśnieniem tętniczym i chorobą niedokrwienną serca cechowali się wyższym od setkiem bardziej zaawansowanej niewydolności nerek. Zależność GFR oraz wieku od rozkurczowego ciśnienia tętniczego u chorych z nadciśnieniem i bez choroby niedokrwiennej serca wskazuje na wartość rokowniczą stopnia wydolności nerek w interpretacji ryzyka sercowo-naczyniowego.Background Hypertension is one of the cardiovascular disease (CVD) risk factors and is present in approximately 70-85% of patients with chronic renal failure. The current Kidney Disease Outcomes Quality Initiative guidelines advocate creatinine-based equations for estimating glomerular filtration rate (GFR) to identify patients with potential chronic kidney disease (CKD) and to classify them into different stages on the basis of these values. Material and methods Assessment of prevalence of CKD using estimating GFR according to Modification of Diet in Renal Disease (MDRD) formula in 58 hospitalized hypertensive patients (20 women and 38 men). They were divided in two groups: A - 28 patients without coronary artery disease (9 women and 19 men) and B - 30 patients with coronary artery disease (11 women and 19 men). Results According to MDRD formula: stage 1 CKD in the group of hypertensive patients without coronary artery disease (A) was found in 25%, whereas in the group of hypertensive patients with coronary artery disease (B) it was found in 6.67%. Stage 2 CKD in the group of hypertensive patients without coronary artery disease (A) was found in 39.29%, whereas in the group of hypertensive patients with coronary artery disease (B) it was found in 50%. Stage 3 CKD in the group of hypertensive patients without coronary artery disease (A) was found in 14.29%, whereas in the group of hypertensive patients with coronary artery disease (B) it was found in 23.33%. Conclusions There is a need to estimate GFR according to MDRD formula, because there isn’t a linear dependence between GFR and creatinine concentration. We have to remember that GFR which gives evidence of chronic kidney disease is considered to be a significant cardiovascular risk factor

How far is the EU from the ‘United States of Europe’?

The European Union was an attempt to concentrate the economic resources of politically and socially independent countries in order to meet the challenges that could arise in case of confrontation with stronger players. From the very beginning, the creators of the idea of integration put the goal: the unification of Europe must be done in the form of a federal structure, and it has been demonstrated by the fact that further reforms reflected the influence of the idea of federalism during the unification process. From a functional perspective, the European countries are today as integrated as the North American states were in the 19th century, but with the difference that the formal statehood of the European Union is still divided in 27 Member States. For the makers of the European Union, federalism was not so much a method of building a united Europe, but the result of its creation process in the form of concrete steps. Steps that have to rely on giving back sector by sector of public activity under the control of transnational bodies. The concept of a clear division of competences between the EU and the Member States seems real, while the proposal of formation of a European government or the creation of the category of "European nation" is still a difficult issue to implement. From this point of view, it seems that the perspectives for the creation of the United States of Europe are still relatively distant.ABSTRACT The European Union came into the world with a vertical organization and centralized control. The answer to the question whether it should focus on integration and harmonization of the following areas of state activity, or to integrate into their ranks as the largest number of new countries, is dependent on how it is defined the final desired form. Opponents of federalization of the EU, focus on the donation, transfer of competences to the European level, the loss of competences and erosion of sovereignty. Its supporters - say that absolute sovereignty in the world today is already a myth and outdated construction, with a federation or not - say rather a common exercise of sovereignty, supporting and complementing the national and European level.Of course you cannot prejudge whether this process federalization of Europe will be achieve in the near future, but the problem of federal future will returning with ever new actuality. Real seems to be the concept of a clear division of competences between the Community and the Member States, while difficult issue to implemented is the proposal of formation the European government or creation the category "European nation". From this point of view, it seems that the prospect of the creation of the United States of Europe is still relatively distant.ResumenLa Unión Europea fue un intento de concentración de recursos económicos de países social y políticamente individuales para afrontar los retos que se plantean en caso de confrontación con jugadores más fuertes. Desde el inicio los creadores de la idea de integración establecieron el objetivo: la unificación de Europa ha de ser bajo la forma de una estructura federal, hecho que viene demostrado por las reformas que se han dado durante el proceso de integración. Desde una perspectiva funcional, los países europeos están ahora igual de integrados que los estados de América del Norte del siglo XIX, pero la principal diferencia radica en el hecho de que la condición formal de Estado de la UE sigue independiente en los 27 Estados miembros. Para los fundadores de la Unión Europea, el federalismo no era tanto un método de construcción de una Europa unida, sino que surgió en todo el proceso de su creación bajo la forma de medidas concretas. Pasos que tienen que ver con la cesión de soberanía nacional en beneficio del control de organismos transnacionales. Real parece ser la clara división de competencias entre la UE y los Estados miembros, mientras que es un asunto difícil aplicar la propuesta de la formación de un gobierno europeo o la creación de la categoría de "nación europea". Desde este punto de vista, parece que la perspectiva de la creación de los Estados Unidos de Europa está aún relativamente lejana

Mapping of DNA methylationsensitive cellular processes in gingival and periodontal ligament fibroblasts in the context of periodontal tissue homeostasis

Interactions between gingival fibroblasts (GFs) and oral pathogens contribute to the chronicity of inflammation in periodontitis. Epigenetic changes in DNA methylation are involved in periodontitis pathogenesis, and recent studies indicate that DNA methyltransferase (DNMT) inhibitors may protect against epithelial barrier disruption and bone resorption. To assess the impact of DNMT inhibition on GFs, cells were cultured with decitabine (5-aza-2’-deoxycytidine, DAC) for 12 days to induce DNA hypomethylation. We observed several potentially detrimental effects of DAC on GF biological functions. First, extended treatment with DAC reduced GF proliferation and induced necrotic cell death. Second, DAC amplified Porphyromonas gingivalis- and cytokine-induced expression and secretion of the chemokine CCL20 and several matrix metalloproteinases (MMPs), including MMP1, MMP9, and MMP13. Similar pro-inflammatory effects of DAC were observed in periodontal ligament fibroblasts. Third, DAC upregulated intercellular adhesion molecule-1 (ICAM-1), which was associated with increased P. gingivalis adherence to GFs and may contribute to bacterial dissemination. Finally, analysis of DAC-induced genes identified by RNA sequencing revealed increased expression of CCL20, CCL5, CCL8, CCL13, TNF, IL1A, IL18, IL33, and CSF3, and showed that the most affected processes were related to immune and inflammatory responses. In contrast, the genes downregulated by DAC were associated with extracellular matrix and collagen fibril organization. Our observations demonstrate that studies of DNMT inhibitors provide important insights into the role of DNA methylation in cells involved in periodontitis pathogenesis. However, the therapeutic potential of hypomethylating agents in periodontal disease may be limited due to their cytotoxic effects on fibroblast populations and stimulation of pro-inflammatory pathways.</p