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Soltysik K.,Medical University of Silesia, Katowice
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society | Year: 2013

The functions of estrogens are relatively well known, however the molecular mechanism of their action is not clear. The classical pathway of estrogen action is dependent on ERα and ERβ which act as transcription factors. The effects of this pathway occur within hours or days. In addition, so-called, non-classical mechanism of steroid action dependent on membrane estrogen receptors (mER) was described. In this mechanism the effects of estrogen action are observed in a much shorter time. Here we review the structure and cellular localization of mER, molecular basis of non-classical mER action, physiological role of mER as well as implications of mER action for cancer biology. Finally, some concerns about the new estrogen receptor - GPER and candidates for estrogen receptors - ER-X and ERx, are briefly discussed. It seems that mER is a complex containing signal proteins (signalosome), as IGF receptor, EGF receptor, Ras protein, adaptor protein Shc, non-receptor kinase c-Src and PI-3K, what rationalizes production of second messengers. Some features of membrane receptors are almost identical if compared to nuclear receptors. Probably, membrane and nuclear estrogen receptors are not separate units, but rather the components of a complex mechanism in which they both cooperate with each other. We conclude that the image of the estrogen receptor as a simple transcription factor is a far-reaching simplification. A better understanding of the mechanisms of estrogen action will help us to design more effective drugs affecting signal pathways depending on both membrane and nuclear receptors. Source


Buldak R.J.,Medical University of Silesia, Katowice
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society | Year: 2013

Visfatin has recently been established as a novel adipokine that is predominantly expressed in visceral fat. Recombinant visfatin has immunomodulating properties, which can activate human leukocytes in vitro to induce cytokine production (IL-1β, TNF-α, and IL-6). Only few studies have investigated the effect of visfatin on prostate, breast, ovarian cancer as well as astrocytoma cell biology. There have been no studies on the cytokine secretion in human melanoma cells in response to visfatin stimulation along with intracellular protein kinases inhibitors. ELISA assay was performed in supernatants of Me45 cells stimulated with visfatin in the presence or the absence of specific pharmacological inhibitors of the indicated protein kinases (p38, MEK 1, PI3k and JAK kinase) and nuclear factor kappa B (NK-κB) inhibitor. Intracellular reactive oxygen species level was measured in 2', 7'-dichlorodihydrofluorescein diacetate (H2DCF-DA)-loaded cells using a fluorescent measurement system. For determination of NF-κB activation, activated NF-κB p65 subunit was determined using an EZ-TFA-detect chemiluminescent transcription factor assay. We report that visfatin led to the significant increase in IL-6 and IL-8 level in culture supernatants of human malignant melanoma Me45 cells. Additionally visfatin resulted in the increase of the intracellular reactive oxygen species level. PI3k and NF-κB pathways were activated upon visfatin stimulation. The results may reflect the fact that PI3k pathway stimulation by visfatin may further lead to NF-κB activation and pro-inflammatory response. Source


Cieslik-Bielecka A.,Medical University of Silesia, Katowice
Journal of biological regulators and homeostatic agents | Year: 2012

Platelets, as main actors of the first stage of the healing process, play an important role in tissue repair. Their granules contain many active substances, particularly over 30 growth factors with significant effects on the resident cells at the site of injury, such as mesenchymal stem cells, chondrocytes, fibroblasts, osteoblasts. This potential may be increased by the concentration of the platelets, using platelet-rich plasma/fibrin products. In the four families of platelet concentrates, 2 families contain also significant concentrations of leukocytes: L-PRP (Leukocyte- and Platelet-Rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich Fibrin). Inductive properties of platelet concentrates were widely described. However, they present also antimicrobial effects. The antibacterial effects of L-PRP were highlighted in only a few in vitro studies. Strong activity comparable to gentamicin and oxacillin for L-PRP against methicillin susceptible Staphylococcus aureus (MSSA) was already demonstrated. L-PRP also inhibited the growth of methicillin resistant Staphylococcus aureus (MRSA) and Escherichia coli. Some authors also reported clinical observations about the reduction of infections and the induction of healing processes after the use of platelet concentrates in cardiac, orthopaedic, oral and maxillofacial surgery. However, very little is yet known about the antibacterial effects of these concentrates. In this manuscript, the current data about the antimicrobial agents and cells present in the platelet-rich plasma/fibrin are highlighted and discussed, in order to introduce this new key chapter of the platelet concentrate technology history. Source


Kukla M.,Medical University of Silesia, Katowice
Hepatology International | Year: 2013

It has become increasingly clear that angiogenesis occurring during chronic wound healing and fibrogenesis provides a key contribution to disease progression and complications. The association of fibrogenesis and angiogenesis should be regarded as crucial in the modern evaluation of liver disease progression and in the search for therapeutic targets. Physiological hepatic angiogenesis occurs during liver regeneration, contributing to the formation of new functional sinusoids. Pathological angiogenesis in liver is characterized by intrahepatic vascular remodeling with capillarization of the sinusoids and development of intrahepatic shunts, which lead to increased hepatic resistance and decreased effective hepatocyte perfusion. The problem of angiogenesis in chronic hepatitis C and nonalcoholic fatty liver disease has not been fully resolved. This manuscript briefly describes pathogenesis of new blood vessel formation in chronic hepatitis and potential role of angiogenesis in disease progression. © 2012 Asian Pacific Association for the Study of the Liver. Source


Kasperska-Zajac A.,Medical University of Silesia, Katowice
Journal of the European Academy of Dermatology and Venereology | Year: 2012

The patterns of acute-phase response (APR) biomarkers differ upon various inflammatory conditions. Little information is available on the systemic inflammatory response in urticaria/angio-oedema. It has been shown that concentrations of circulating APR biomarkers, IL-6 and C-reactive protein (CRP), are elevated more in severe chronic urticaria (CU) than in patients showing milder urticarial symptoms. It is not clear whether the increase of IL-6 and CRP is merely an epiphenomenon or may contribute to the pathogenesis of CU. It is tempting to speculate that mediators of APR may enhance urticarial inflammation. In addition, there is some association between APR and activation of coagulation/fibrinolysis in CU. It is well known that even slight elevation in CRP baseline concentration is enough to produce significant increase in cardiovascular risk. In this light, one should ask whether CU patients, in particular those showing stronger systemic inflammatory response and long-lasting course are more vulnerable to the cardiovascular events. Apart from highly troublesome symptoms and low quality of life, CU may then involve some remote, serious systemic consequences. Taken together, CU can be identified as a mast cell- and basophil-dependent inflammatory disorder of the skin, which is accompanied by APR. Characterization of APR in CU may appear essential for an insight into the activity of this disease and for assessment of the inflammation degree. Moreover, measurement of these biomarkers might be particularly relevant while assessing CU patients demanding an anti-inflammatory or immunosuppressive therapy. This review summarizes information regarding APR in the course of urticaria/angio-oedema. © 2011 European Academy of Dermatology and Venereology. Source

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