The article addresses the topic of alternative legal models for pursuing out-of-court claims for medical damages, taking as its starting thesis the inefficiency of the Polish model stemming from its ...faulty legal construction. The purpose of the article is to conduct a legal analysis of the Polish alternative model of medical damage compensation, with particular attention to de lege ferenda postulates presented in the legal doctrine. In addition, in order to show the possible directions of legislative changes, the article presents the characteristics of selected foreign alternative models of medical damage compensation, including the model operating in New Zealand, which is an example of a model that can be classified as ‘no-fault’, the German model and the French model. The article culminates with an analysis of the draft of the Law on Quality in Health Care and Patient Safety to the extent that the draft provides for a new legal regulation of the alternative model for the out-of-court settlement of medical damage claims. The purpose of this analysis was to see whether the legislator has recognized the demands for change articulated in the legal doctrine, and whether the draft law on quality in health care and patient safety is inspired by solutions adopted in foreign legislation in terms of the legal construction of the alternative model of compensation for medical damages. The analysis here confirms the initial thesis of the work and leads to the conclusion that the draft law on quality in health care and patient safety takes into account many proposals constructed in the legal doctrine in connection with regulating an alternative model for the compensation of medical damages. It is also clear that the proposed model is inspired by some solutions that have been successful in other countries. Nevertheless, the article distinguishes proposed regulations that may still raise doubts and reservations.
•Polysaccharides of rape straw and miscanthus were hydrolyzed with hydrolytic enzymes.•Experiments were conducted with native and alkaline pretreated substrates.•The study demonstrates a significant ...impact of xylanases on the hydrolysis yield.
The research was carried out with the aim to determine the impact of various combinations of cellulase and hemicellulase preparations on the effectiveness of enzymatic hydrolysis of polysaccharides of rape straw and Miscanthus giganteus after alkaline pretreatment. Their effectiveness was evaluated based on the quantity of saccharides released during enzymatic reaction and yield calculated in respect of the sum of polysaccharides present in native substrates. The complex of preparations produced from Trichoderma longibrachiatum fungi turned out to be the most effective. The study demonstrated a significant effect of xylanases from T. longibrachiatum, the presence of which evoked a 27–45% increase in the effectiveness of polysaccharides hydrolysis compared to the enzymatic complexes without their addition. In addition, results achieved in this study confirmed the necessity of applying the pretreatment in lignocellulose substrates conversion into bioethanol.
JAK (Janus kinase)/STAT (signal transducers and activators of transcription) signaling is involved in the regulation of cell growth, differentiation and apoptosis. Constitutive activation of STATs, ...in particular STAT3, is observed in a large number of human tumors, including gliomas and may contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis, thus it emerges as a promising target for anti-cancer therapy. To investigate the therapeutic potential of blocking STAT3 in glioma cells a set of small synthetic molecules - caffeic acid derivatives, structurally related to AG490 was screened for its ability to inhibit STAT3. Inhibitor 2 (E)-2-cyano-N-(S)-1-phenylethyl-3-(pyridin-2-yl)acrylamide was the most effective in inhibition of JAK/STAT3 signaling and at doses ≥ 25 μM significantly reduced the level of phosphorylated JAK1, JAK2 and STAT3 (at Tyr705) and downregulated the expression of known STAT3 targets. In treated cells we observed rapid detachment and rounding of cells associated with reduction of focal adhesion kinase phosphorylation and activity, followed by upregulation of phosphorylated p38, JNK and ERK1/2 levels. Accumulation of cells with fragmented DNA, increases of the cleaved caspase 3 and fragmented PARP levels were detected 24 h after the treatment suggesting ongoing apoptotic cell death. Three human malignant glioblastoma cell lines defective in tumor suppressors TP53 and/or PTEN were susceptible to inhibitor 2 that induced the programmed cell death. Global gene expression profiling revealed modulation of numerous genes in cells treated with inhibitor 2 revealing novel, potential JAK/STAT targets. Our study demonstrates that suitably modified caffeic acid molecules exhibit significant cytotoxic potential toward glioma cells.
STAT Signaling in Glioma Cells Swiatek-Machado, Karolina; Kaminska, Bozena
Advances in experimental medicine and biology,
01/2020, Letnik:
1202
Journal Article
Recenzirano
STAT (signal transducers and activators of transcription) are latent cytoplasmic transcription factors that function as downstream effectors of cytokine and growth factor receptor signaling. The ...canonical JAK/STAT signaling pathway involves the activation of Janus kinases (JAK) or growth factors receptor kinases, phosphorylation of STAT proteins, their dimerization and translocation into the nucleus where STATs act as transcription factors with pleiotropic downstream effects. STAT signaling is tightly controlled with restricted kinetics due to action of its negative regulators. While STAT1 is believed to play an important role in growth arrest and apoptosis, and to act as a tumor suppressor, STAT3 and 5 are involved in promoting cell cycle progression, cellular transformation, and preventing apoptosis. Aberrant activation of STATs, in particular STAT3 and STAT5, have been found in a large number of human tumors, including gliomas and may contribute to oncogenesis. In this chapter, we have (1) summarized the mechanisms of STAT activation in normal and malignant signaling; (2) discussed evidence for the critical role of constitutively activated STAT3 and STAT5 in glioma pathobiology; (3) disclosed molecular and pharmacological strategies to interfere with STAT signaling for potential therapeutic intervention in gliomas.
Self-assembled monolayers of α-helical peptides on a gold surface were employed as model systems for the investigation of mediated electron transfer. The peptides contained 14, 15, 16, and 17 amino ...acid residues. The measurements of electron transmission through single molecules of helical peptides were performed using scanning tunneling spectroscopy (STS). The molecules were trapped between the gold tip and the substrate. Electrical contact between the molecule and the gold probe was achieved by the use of peptides containing thiol groups present at each end of the helix. The conductance behavior of the peptides was examined as a function of tip−substrate distance at fixed bias voltage. Measurements performed with peptides containing different numbers of amino acid residues indicate that the distance dependence of electron transmission through an α-helix is weaker than that through simple n-alkyl bridges.
We synthesized an α-helical peptide containing two terminal thiol groups and demonstrated the method of preparation of a self-assembled monolayer (SAM) on gold with uniform orientation of the ...molecules on the surface. The monolayers were employed as model systems for the investigations of mediated electron transfer. The measurements of electron transfer efficiency through the peptide were performed using scanning tunneling spectroscopy (STS). The molecules were trapped between the gold tip and the substrate using a Au−S linkage. The electron transfer behavior of the peptide was examined as a function of the tip−substrate distance at fixed bias voltage and as a function of bias voltage at a fixed distance between the tip and the substrate. The data obtained from these experiments indicated that the electron transfer through α-helical peptide is very efficient, and its conductivity is comparable to those observed for dodecanedithiol. There is also a directional dependence of electron transmission through the peptide, which is connected with the electric field generated by the molecular dipole of the helix.
STAT signaling in glioma cells Swiatek-Machado, Karolina; Kaminska, Bozena
Advances in experimental medicine and biology,
01/2013, Letnik:
986
Journal Article
Recenzirano
STAT (signal transducers and activators of transcription) are latent cytoplasmic transcription factors that function as downstream effectors of cytokine and growth factor receptor signaling. The ...canonical JAK/STAT signaling pathway involves the activation of Janus kinases (JAK) or growth factors receptor kinases, phosphorylation of STAT proteins, their dimerization and translocation into the nucleus where STATs act as transcription factors with pleiotropic downstream effects. STAT signaling is tightly controlled with restricted kinetics due to action of its negative regulators. While STAT1 is believed to play an important role in growth arrest and apoptosis, and to act as a tumor suppressor, STAT3 and 5 are involved in promoting cell cycle progression, cellular transformation, and preventing apoptosis. Aberrant activation of STATs, in particular STAT3 and STAT5, have been found in a large number of human tumors, including gliomas and may contribute to oncogenesis. In this chapter, we have (1) summarized the mechanisms of STAT activation in normal and malignant signaling; (2) discussed evidence for the critical role of constitutively activated STAT3 and STAT5 in glioma pathobiology; (3) disclosed molecular and pharmacological strategies to interfere with STAT signaling for potential therapeutic intervention in gliomas.
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