J. Veteskova, M. Obsivan, Z. Kmecova, M. Radik, J. Srankova, E. Malikova, J. Klimas and P. Krenek
Aim: Chemokine stromal cell derived factor-1 (SDF-1) plays an important role in many processes such as apoptosis, proliferation, migration and angiogenesis, and these effects are mediated mostly by the receptor CXCR4. The aim of this study was to determine the expression of SDF-1 and CXCR4 in the ventricles of rats with monocrotaline-induced pulmonary hypertension.
Methods: 10–12 weeks old male Wistar rats were injected with monocrotaline (s. c., 60mg/kg; MON) or vehicle (CON). Rats were sacrificed 1 week (1W-MON, 1W-CON), 2 weeks (2W-MON, 2W-CON) and 4 weeks after monocrotaline administration (4W-MON, 4W-CON). Gene expression of SDF-1 and CXCR4 was determined by qRT-PCR.
Results: We observed a decrease in the SDF-1 expression on mRNA level in the right ventricle in 2W-MON and 4W-MON rats without any changes in the left ventricles and a decrease in CXCR4 expression in 1W-MON in both ventricles with an increase of CXCR4 expression in 4W-MON in the left ventricle (*P ˂ 0.05).
Conclusion: SDF-1/CXCR4 axis is affected in both ventricles of rats with monocrotaline model of pulmonary hypertension.
Our previous reports showed that the cyclic-AMP-response element-binding protein (CREB) served as a proto-oncogene in the process of tumorigenesis and mediated the growth and metastatic activity of renal cancer cells. Our study, therefore, explored the role of CREB in sorafenib- -inhibited cell proliferation, migration and invasion. Renal cancer cells were cultured in medium containing sorafenib for 12, 24, 48 and 72 h. The MTT assay was used to study the cytotoxic effects of sorafenib. Cell invasion and migration were assayed in wound healing and transwell experiments, respectively. Protein expression levels were evaluated by western blotting. The results show that sorafenib treatment decreased cell viability in a dose- and time-dependent manner. Sorafenib inhibited cell migration and invasion and decreased the expression of MMP-2 and MMP-9. Moreover, addition of the recombinant plasmid pCI-neo/ CREB (PN) reversed the sorafenib-induced inhibition of cell proliferation, migration and invasion. These results show that CREB is associated with the sorafenib-induced inhibition of proliferation, migration and invasion.
M. Kocmálová, J. Ľupták, J. Barboríková, I. Kazimierová, M. Grendár and J. Šutovský
Background: This study specified the role of several significant ion channels regulating the metabolism of calcium ions in contraction and relaxation of human detrusor muscle in order to identify possible target for future drugs that are capable of treating diseases resulting from impaired detrusor activity, e.g. overactive bladder. Although this disease can be successfully treated with muscarinic receptor antagonists or β3 agonist, many patients may not be suitable for chronic therapy, especially due to the relatively high side effects of the treatment.
Material and Methods: The study used the isolated detrusor tissue samples, which were obtained from the macroscopic healthy tissue of urinary bladder from 19 patients undergoing a total prostatectomy because of localized prostate cancer. Each biological sample was prepared into 8 strips. We used oxybutynin and mirabegron as control drugs and several blockers of specific subtypes calcium and potassium ion channels as tested substances. The contractility of bladder was investigated by an organ tissue bath method in vitro and contraction was induced by carbachol.
Results: The amplitude of contraction was successfully decreased by positive control drugs and, from tested agents, the comparable effect had the substance capable of influencing IP3 receptors and Orai-STIM channels and combination consisting of drugs possessing an inhibitory effect on IP3 receptors, L- and T-type voltage-gated calcium channels and Orai-STIM channels.
Conclusion: The present work represents a new finding about handling Ca2+ in urinary bladder contraction and pointed to a dominant role of IP3 receptor-mediated pathway in the regulation of Ca2+ metabolism, which may represent a future strategy in pharmacotherapy of impaired detrusor activity.
, Giacomini M, Gaillard RC. Transient sex-related changes in the mice hypothalamopituitary- adrenal (HPA) axis during the acute phase of the inflammatory process. Mediators Inflamm. 1993;2:123-127.
 Franklin M, Hlavacova N, Babic S, Pokusa M, Bermudez I, Jezova D. Aldosterone Signals the Onset of Depressive Behaviour in a Female Rat Model of Depression along with SSRI Treatment Resistance. Neuroendocrinology. 2015;102:274-287.
 Jezova D, Jurankova E, Mosnarova A, Kriska M, Skultetyova I. Neuroendocrine response during stress with
Priyanshee Gohil, Himani Thakkar, Unnati Gohil and Shrikalp Deshpande
inflammatory bowel disease, Mediators Inflamm. 7 (1998) 157-162; DOI: 0962-9351/98/030157-06.
C. D. Kim, Y. K. Kim and S. H. Lee, Rebamipide inhibits neutrophil adhesion to hypoxia/re-oxygenation stimulated endothelial cells via nuclear factor-κB dependent pathway, J. Pharmacol. Exp. Ther. 294 (2000) 864-869; DOI: 0022-3565/00/2943-0864.
J. Y. Ro, J. Y. Kim and K. H. Kim, The inhibitory mechanism of rebamipide on the mediator release in the guinea pig lung mast cells activated with specific antigen
Gongwen Liang, Na Li, Liping Ma, Zhonglian Qian, Yuwen Sun, Luwen Shi and Libo Zhao
. DeArmond and S. B. Prusiner, Pharmacokinetics of quinacrine efflux from mouse brain via the P-glycoprotein efflux transporter, PLoS One 7 (2012) e39112; DOI: 10.1371/journal.pone.0039112.
4. D. Pal, D. Kwatra, M. Minocha, D. K. Paturi, B. Budda and A. K. Mitra, Efflux transporters- and cytochrome P-450-mediated interactions between drugs of abuse and antiretrovirals, Life Sci. 88 (2011) 959–971; DOI: 10.1016/j.lfs.2010.09.012.
5. A. Antinori, G. Arendt, J. T. Becker, B. J. Brew, D. A. Byrd, M. Cherner, D. B. Clifford, P. Cinque, L. G. Epstein, K
Veronika Kováčiková, Marek Obložinský, Renáta Kollárová, Lýdia Bezáková, Katarína Šišková and Ingrid Pauliková
] Radmark O, Werz O, Steinhilber D. 5-Lipoxygenase: regulation
of expression and enzyme activity. Trends Biochem.
 Riccioni G, Zanasi A, Vitulano N, Mancini B, D’orazio N.
Leukotrienes in Atherosclerosis: New Target Insights
and Future Therapy Perspectives. Mediators of Inflamm.
2009;Article ID 737282, 6 pages.
 Romano M. Lipid mediators: lipoxin and aspirin-triggered
15-epi-lipoxins. Inflamm. Allergy Drug Targets 2006;5:
 Schindler CH. The metabolic
Martin Ambrož, Markéta Šmatová, Michaela Šadibolová, Eva Pospíšilová, Pavlína Hadravská, Michaela Kašparová, Veronika Hanušová Skarková, Věra Králová and Lenka Skálová
bladder cancer cells is mediated through ROS generation and mitochondrial dysfunction, Molecules 18 (2013) 1418–1433; https://doi.org/10.3390/molecules18021418
11. Y. S. Sun, L. X. Lv, Z. Zhao, X. He, L. You, J. K. Liu and Y. Q. Li, Cordycepol C induces caspase-independent apoptosis in human hepatocellular carcinoma HepG2 cells, Biol. Pharm. Bull . 37 (2014) 608–617.
12. T. C. Chou, Drug combination studies and their synergy quantification using the Chou-Talalay method, Cancer Res . 70 (2010) 440–446; https://doi.org/10.1158/0008-5472.CAN-09
Zhaoxiang Zhou, Meng Wang, Zengjun Guo and Xiaoying Zhang
. 23 (1999) 991-1007; DOI: 10.1111/j.1530-0277.1999.tb04217.x.
13. V. Breinholt, E. A. Offord, C. Brouwer, S. E. Nielsen, K. Brøsen and T. Friedberg, In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids, Food Chem. Toxicol. 40 (2002) 609-616; DOI: 10.1016/S0278-6915(01)00125-9.
14. D. Pal and A. K. Mitra, MDR- and CYP3A4-mediated drug-herbal interactions, Life Sci. 78 (2006) 2131-2145; DOI: 10.1016/j.lfs.2005.12.010.
15. T. Y. Shih, T. H. Young, H. S. Lee, C. B. Hsieh and O. Y. Hu
Kateřina Lněničková, Lenka Skálová, Lucie Stuchlíková, Barbora Szotáková and Petra Matoušková
, Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism, Cancer Res. 63 (2003) 5513-5520.
15. M. D. Burke and R. T. Mayer, Ethoxyresorufin: direct fluorimetric assay of a microsomal O-dealkylation which is preferentially inducible by 3-methylcholanthrene, Drug Metab. Dispos. 2 (1974) 583-588.
16. A. Untergasser, I. Cutcutache, T. Koressaar, J. Ye, B. C. Faircloth, M. Remm and S. G. Rozen, Primer3 - new capabilities and interfaces, Nucleic Acids Res. 40 (2012) e