New histone deacetylase inhibitors as potential therapeutic tools for advanced prostate carcinoma

The anti-epileptic drug valproic acid is also under trial as an anti-cancer agent due to its histone deacetylase (HDAC) inhibitory properties. However, the effects of valproic acid (VPA) are limited and concentrations required for exerting anti-neoplastic effects in vitro may not be reached in tumour patients. In this study, we tested in vitro and in vivo effects of two VPA-derivatives (ACS2, ACS33) on pre-clinical prostate cancer models. PC3 and DU-145 prostate tumour cell lines were treated with various concentrations of ACS2 or ACS33 to perform in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and to evaluate tumour cell adhesion to endothelial cell monolayers. Analysis of acetylated histones H3 and H4 protein expression was performed by western blotting. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. Tumour sections were assessed by immunohistochemistry for histone H3 acetylation and proliferation. ACS2 and ACS33 significantly up-regulated histone H3 and H4 acetylation in prostate cancer cell lines. In micromolar concentrations both compounds exerted growth arrest in PC3 and DU-145 cells and prevented tumour cell attachment to endothelium. In vivo, ACS33 inhibited the growth of PC3 in subcutaneous xenografts. Immunohistochemistry and western blotting confirmed increased histone H3 acetylation and reduced proliferation. ACS2 and ACS33 represent novel VPA derivatives with superior anti-tumoural activities, compared to the mother compound. This investigation lends support to the clinical testing of ACS2 or ACS33 for the treatment of prostate cancer

Physical and Mechanical Properties of an Artificial Aggregate Made up of Ground Granulated Blast-Furnace Slag

Manufacturing artificial aggregate by utilizing waste materials has gained great importance as the aggregate occupies a high volume in concrete (60–70%). In this paper, ground granulated blast furnace slag (GGBFS) is utilized in aggregate manufacturing. Cold bonding and sintering methods were used as production processes. The pellets were put through a series of tests like dry density, specific gravity, water absorption, and crushing strength. The results indicated that the density of pellets increased by increasing the GGBFS dosage while the water absorption capacity was reduced. Furthermore, the highest crushed strength was recorded at 50% addition of GGBFS

Targeting sustainable competitiveness in Croatia by implementation of “20 Keys” methodology

Throughout the current wave of regulatory reforms, several theoretical models have been proposed that call for the emergence of instruments of self-regulation under some form of state supervision as part of the demand to improve product development performances aligned with awareness of environmental needs, to help with meeting regulation and to reduce the risk of production nonconformance. “20 Keys” is one example of a mass application of a methodology for raising sustainable development and holistic approach to competitiveness in new EU member the Republic of Croatia, and therefore, the aim of this study is to observe the results of the methodology application in Croatian companies. 20 Keys is a methodology that brings an integrated set of tools aimed at increasing overall productive efficiency and quality level with simultaneous reduction of costs. As it was shown in this paper, implementation success is coincident with senior management’s active role in setting the main goals for implementation, assuring that suitable methods and tools are used, allocating resources appropriately and enabling communication within the company

The histone deacetylase inhibitor valproic acid alters growth properties of renal cell carcinoma in vitro and in vivo

Histone deacetylase (HDAC) inhibitors represent a promising class of antineoplastic agents which affect tumour growth, differentiation and invasion. The effects of the HDAC inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre-clinical renal cell carcinoma (RCC) models. Caki-1, KTC-26 or A498 cells were treated with various concentrations of VPA during in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and to evaluate cell cycle manipulation. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. The anti-tumoural potential of VPA combined with low-dosed interferon-α (IFN-α) was also investigated. VPA significantly and dose-dependently up-regulated histones H3 and H4 acetylation and caused growth arrest in RCC cells. VPA altered cell cycle regulating proteins, in particular CDK2, cyclin B, cyclin D3, p21 and Rb. In vivo, VPA significantly inhibited the growth of Caki-1 in subcutaneous xenografts, accompanied by a strong accumulation of p21 and bax in tissue specimens of VPA-treated animals. VPA–IFN-α combination markedly enhanced the effects of VPA monotherapy on RCC proliferation in vitro, but did not further enhance the anti-tumoural potential of VPA in vivo. VPA was found to have profound effects on RCC cell growth, lending support to the initiation of clinical testing of VPA for treating advanced RCC

The mediating role of self/everyday creativity and depression on the relationship between creative personality traits and problematic social media use among emerging adults

Personality is one of the important contributory factors in the development of problematic technology use. The purpose of the present study was to investigate the direct and indirect associations of creative personality traits with problematic social media use via self/everyday creativity, depression, and loneliness. A total of 460 Turkish emerging adults aged between 18 and 26 years (61% female) were surveyed. Findings indicated that (i) task-orientedness was indirectly associated with problematic social media use via self/everyday creativity, (ii) self-confidence was directly and indirectly associated with problematic social media use via self/everyday creativity and depression, (iii) risk-taking was indirectly associated with problematic social media use via depression, and (iv) self/everyday creativity and depression were directly associated with problematic social media use. The present study is the first to suggest that creative personality traits (i.e., task-orientedness, self-confidence, and risk-taking) and self/everyday creativity are associated with problematic social media use and that these factors should be taken into account when considering the etiology of problematic social media use

On the size of two families of unlabeled bipartite graphs

Let Bu(n,r) denote the set of unlabeled bipartite graphs whose edges connect a set of n vertices with a set of r vertices. In this paper, we provide exact formulas for |Bu(2,r)| and |Bu(3,r)| using Polya's Counting Theorem. Extending these results to n≥4 involves solving a set of complex recurrences and remains open. In particular, the number of recurrences that must be solved to compute |Bu(n,r)| is given by the number of partitions of n that is known to increase exponentially with n by Ramanujan-Hardy-Rademacher's asymptotic formula. © 2017 Kalasalingam University