Identification of CXCL8c.105A>G and CXCL8c.210C>T polymorphism in Polish HF cattle

Background: Bovine chemokine C-X-C motif legend 8 (CXCL8) also known as interleukin 8 (IL8) is a chemotactic factor that attracts neutrophils, basophils, and T-cells, in response to an inflammatory stimulus. The aim of this study was to investigate the novel single nucleotide polymorphisms (SNPs) located at the promoter region of CXCL8 gene in Polish Holstein Friesian (HF) bulls.Methods: Genotypic profiling of CXCL8c.105A>G and CXCL8c.210C>T SNP polymorphism were carried out by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) methods using HpyCH4VI and RsaI restriction enzymes. Polymorphism study was conducted on 151 randomly selected Polish HF bulls.Results: The genotype frequencies of CXCL8c.105A>G SNPs polymorphism in the investigated Polish HF bulls were observed as 0.24%, 0.5% and 0.26% respectively, whereas, the genotype frequencies of CXCL8c.210C>T SNPs polymorphism were observed as 0.27%, 0.5% and 0.23% respectively. Overall, the allele frequencies were recorded higher for “G’ allele for CXCL8c.105A>G and “C” allele and CXCL8c.210C>T SNP polymorphism. In both investigated SNP polymorphism, the state of genetic equilibrium was maintained in Polish HF bulls. Overall, the obtained results identified four haplotypes with the highest frequencies of CG (0.493%) and TA (0.476%) haplotypes, and the lowest frequencies of CA (0.02%) and TG (0.01%) haplotypes, respectively.Conclusions: Study concludes that both polymorphism could be further investigated for the trait-associated studies in the breeding population of Polish HF cattle

The cytotoxic effect of copper (II) complexes with halogenated 1,3-disubstituted arylthioureas on cancer and bacterial cells

A series of eight copper (II) complexes with 3-(4-chloro-3-nitrophenyl)thiourea were designed and synthesized. The cytotoxic activity of all compounds was assessed in three human cancer cell lines (SW480, SW620, PC3) and human normal keratinocytes (HaCaT). The complexes 1, 3, 5, 7 and 8 were cytotoxic to the studied tumor cells in the low micromolar range, without affecting the normal cells. The complexes 1, 3, 7 and 8 induced lactate dehydrogenase (LDH) release in all cancer cell lines, but not in the HaCaT cells. They provoked early apoptosis in pathological cells, especially in SW480 and PC3 cells. The ability of compounds 1, 3, 7 and 8 to diminish interleukin-6 (IL-6) concentration in a cell was established. For the first time, the influence of the most promising Cu (II) complexes on intensities of detoxifying and reactive oxygen species (ROS) scavenging the enzymes of tumor cells was studied. The cytotoxic effect of all copper (II) conjugates against standard and hospital bacterial strains was also proved

The pipecolic linker - a new handle for the synthesis of new serotonin receptors ligands on solid phase

Prezentowana praca obejmuje dwie główne części. Pierwszą jest wstęp, w którym nakreślono podstawowe zagadnienia dotyczące receptorów serotoninowych typu 6, ich roli w psychiatrycznych zaburzeniach ośrodkowego układu nerwowego takich jak schizofrenia, lęk i depresja, oraz w chorobie Alzheimera i otyłości. Kolejno, dokonano charakterystyki ligandów receptora 5-HT6, o cechach agonistów i antagonistów, oraz zaprezentowano związki będące przedmiotem badań klinicznych.W części doświadczalnej niniejszej pracy opisano syntezę zaprojektowanych serii związków, jako potencjalnych ligandów receptora 5-HT6. Związki uzyskano realizując syntezę na nośniku polimerowym zaopatrzonym w linker pipekolowy – nowe narzędzia do syntezy związków organicznych na fazach stałych. Pierwszą grupę (12 związków) stanowiły amidowe pochodne N-sufamoiloaminokwasów, natomiast drugą (14 związków), analogi kwasu 2-arylo-pirolo-3-karboksylowego i amin alicyklicznych, modyfikowane fragmentami arylosulfonowymi.Realizując zamierzony cel, w pierwszym etapie przygotowano linker pipekolowy na żywicy aminometylopolistyrenowej. Następnie, w wyniku wieloetapowych syntez, stosując m.in. w reakcji amidowania nowoczesne czynniki aktywujące – HATU i COMU oraz strategię manewrowania grupami protekcyjnymi, otrzymano zaplanowane połączenia. Związki oczyszczono metodą wysokosprawnej preparatywnej chromatografii cieczowej, a struktury w sposób niepodważalny potwierdzono analizą widm LC/MS oraz magnetycznego rezonansu jądrowego (1H NMR i 13C NMR).Produkty finalne przekazano do Zakładu Chemii Leków Instytutu Farmakologii Polskiej Akademii Nauk, celem wykonania testów biologicznych określających ich powinowactwo do receptorów serotoninowych typu 6.The present work is consisted of two main parts. In the introduction, the basic concepts of 5-HT6 receptors, their role in psychiatric disorders of the central nervous system such as schizophrenia, anxiety, and depression, as well as Alzheimer's disease and obesity were outlined. Subsequently, the 5-HT6 receptor agonsits and antagonists, followed by the compounds being currently under clinical trials,were described.The aim of the study was the synthesis of two, designed series of compounds, as potential 5-HT6 receptor ligands. The compounds were synthesized according to the multi-step solid-supported methodology using the pipecolic linker (a new handle for the synthesis of organic compounds on solid phase). The first group (12 compounds) consisted in amide derivatives of N-sufamoiloaminoacids, while the second (14 compounds) were classified as arylsulfonamide analogs of 2-aryl-pyrrole-3-carboxylic acid amides.In the first stage, the pipecolic linker was synthetized on aminomethylpolystyrene resin. Then, using a modern activating agents such as HATU and COMU designed molecules were synthesized in a multistage reactions.The final products were purified using high performance preparative chromatography, and the chemical structures were confirmed using LC/MS and nuclear magnetic resonance (1H NMR and 13C NMR).All the synthesized designed compounds were submitted to the Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences for evaluation for their affinity for 5-HT6 receptors

Effect of Mo on stability of quasicrystalline phase in Al-Mn-Fe alloy

Microstructure evolution in rapidly solidified Al91Mn 6Fe2Mo1 ribbons after annealing was investigated using X-ray diffraction, scanning electron microscopy and analytical transmission electron microscopy including in situ heating experiment in TEM. As spun ribbons consisted of icosahedral quasicrystalline particles enriched in Fe, Mn and Mo embedded in an aluminium matrix. A small amount of quasicrystals containing Fe and Mn which coexisted with the Al3(Fe, Mn) phase was also observed between the aluminium grains. Further annealing experiments and subsequent analysis of microstructure changes in the sample showed that the quasicrystalline particles underwent a transformation into stable crystalline phases at temperatures which depended on their composition. It was observed that quasicrystals enriched in Mn and Fe transformed at much lower temperatures than primary quasicrystals with Mo content. It was noticed that two different crystalline phases formed in dependence on the temperature of annealing. The Al6(Mn, Fe) phase appeared first at the quasicrystal/matrix interface. At higher temperature, the Al12(Mn, Mo) phase formed due to reaction of the Al6(Mn, Fe) phase with the aluminium matrix. Microstructural and DSC investigations showed that addition of molybdenum improved thermal stability of the quasicrystals in Al-Mn-Fe system. © 2012 Elsevier B.V. All rights reserved

SEM and TEM Characterization of NiAl2O4 Spinel Phase in Al2O3 Matrix Ni Composite

score: 0collation: 222-22