The Candidate Oncogene CYP24A1: A Potential Biomarker for Colorectal Tumorigenesis

The main autocrine/paracrine role of the active metabolite of vitamin D₃, 1α,25-dihydroxyvitamin D₃ (1,25-D₃), is inhibition of cell growth and induction of cell differentiation and/or apoptosis. Synthesis and degradation of the secosteroid occurs not only in the kidney but also in normal tissue or malignant extrarenal tissues such as the colon. Because 25-hydroxyvitamin D₃ 24-hydroxylase (CYP24A1) is considered to be the main enzyme determining the biological half-life of 1,25-D₃, we have examined expression of the CYP24A1 mRNA (by real-time RT-PCR) and protein (by immunohistochemistry) in normal human colon mucosa, colorectal adenomas, and adenocarcinomas in 111 patients. Although 76% of the normal and benign colonic tissue was either completely devoid of or expressed very low levels of CYP24A1, in the majority of the adenocarcinomas (69%), the enzyme was present at high concentrations. A parallel increased expression of the proliferation marker Ki-67 in the same samples suggests that overexpression of CYP24A1 reduced local 1,25-D₃ availability, decreasing its antiproliferative effect. (J Histochem Cytochem 58:277–285, 2010)     

Conserved structure of the chloroplast-DNA encoded D1 protein is essential for effective photoprotection via non-photochemical thermal dissipation in higher plants

Naturally selected atrazine-resistant (AR) weeds possessing a Ser₂₆₄ → Gly D1 protein encoded by a mutant psbA allele in the chloroplast-DNA have increased photosensitivity and lower fitness. The D1 mutant lines of S. nigrum revealed impaired regulation of photosystem II (PSII) activity as compared with the wild-type plants resulting in a less effective photochemical light utilization and in addition, a lower capacity of non-photochemical thermal dissipation (NPQ), one of the main photoprotective mechanisms in oxygenic photosynthetic organisms. In this work, comparative chlorophyll fluorescence analysis in attached leaves of wild-type and AR Solanum nigrum L. and in their reciprocal crosses has been used to establish how the lower NPQ is inherited. Both a 50% reduction in steady-state NPQ and a 60–70% reduction in the rapidly reversible, energy-dependent (qE) component of NPQ were common phenomena in the parent and hybrid lines of D1 mutant S. nigrum. The nuclear hybrid status of the F2 plant material was confirmed by morphological observations on fully developed leaves. No alteration was found in the nucleotide sequence and the deduced amino acid sequences of the nuclear psbS gene isolated from different biotypes of S. nigrum, and there were no differences in the expressions of both the PsbS and the D1 proteins. All things considered, co-inheritance of the lower photoprotective NPQ capacity and the Ser₂₆₄ → Gly D1 protein mutation was clearly observed, suggesting that the evolutionarily conserved D1 structure must be indispensable for the efficient NPQ process in higher plants.     

Late Quaternary woolly mammoth (Mammuthus primigenius Blum) remains from southern Transdanubia,Hungary

Six samples of subfossil tusk, bone and tooth remains from the woolly mammoth (Mammuthus primigenius Blum) were discovered in south-western Hungary. The remains are relatively well preserved in a Late Pleistocene loess deposit. The samples have been radiocarbon dated (AMS) and are of Late Weichselian (MIS 2) age (21.8–24.1 ka cal BP). The skull fragments, the tusks and maxillary teeth are in close proximity to associated postcranial remains, indicating that the mammoth died where it was found. The size and characteristics of skeletal elements have allowed us to determine that this was a mature male of about 38 years of age.     

Navigating a tool end in a specific direction: stick-tool use in kea (Nestor notabilis)

This study depicts how captive kea, New Zealand parrots, which are not known to use tools in the wild, employ a stick-tool to retrieve a food reward after receiving demonstration trials. Four out of six animals succeeded in doing so despite physical (beak curvature) and ecological (no stick-like materials used during nest construction) constraints when handling elongated objects. We further demonstrate that the same animals can thereafter direct the functional end of a stick-tool into a desired direction, aiming at a positive option while avoiding a negative one.     

The synthesis of 13α-androsta-5,16-diene derivatives with carboxylic acid,ester and carboxamido functionalities at position-17 via palladium-catalyzed carbonylation

17-Alkoxycarbonyl- and 17-carboxamido-3β-hydroxy-13α-androsta-5,16-diene derivatives were synthetized in high yields in the palladium-catalyzed carbonylation reactions of the corresponding 3β-hydroxy-17-iodo-13α-androsta-5,16-diene. This substrate with a 17-iodo-16-ene functionality was obtained from the 17-keto derivative via its 17-hydrazone, which was treated with iodine in the presence of a base (1,1,3,3-tetramethylguanidine). 17-Carboxamides were obtained by chemoselective aminocarbonylation through the use of amines, including amino acid esters, as N-nucleophiles. The 17-methoxycarbonyl-16-ene derivative was synthetized by using methanol as O-nucleophile. The parent compound of this series, the 17-carboxylic acid derivative, was formed in the presence of water via hydroxycarbonylation.     

Atropine-induced gastrointestinal cytoprotection dependences to the intact of vagal nerve against indomethacin-induced gastrointestinal mucosal and microvascular damage in rats

The non-steroidal antiinflammatory drugs, such as an indomethacin (IND), cause mucosal ulceration and increase the mucosal vascular permeability in the gastrointestinal (GI) tract. Some exogenous agents, e.g. the atropine, can protect the GI mucosa against these ulcerogenic effects. The gastrointestinal functions and mucosal protection, however, are regulated by the vagal nerve. The aims of this study was to examine the dependence of atropine-induced GI cytoprotection to the vagal innervation against the development of IND-caused ulcers and microvascular damage in the mucosa of stomach and small intestine in rats. METHODS: the observations were carried out on CFY-strain rats. The mucosal damage was produced by subcutaneous administration of IND in a 20 mg/kg dose 24 h prior to the killing of animals at the same time as the start of atropine-application, which was given in a small dose (0.1 mg/kg) every 5 h. The subdiaphragmatic bilateral surgical vagotomy was done 24 h before the experiment. The vascular permeability, indicated by the microvascular endothel damage, was measured by the appearance and concentration of intravenously administered Evans blue into the GI mucosa. The number and severity of mucosal lesions and the Evans blue content of mucosa were determined in the stomach and small intestine. RESULTS: (1) The IND caused mucosal ulcers and Evans blue extravasation into the mucosa of the stomach and small intestine. (2) The IND-induced mucosal ulceration and vascular permeability significantly decreased after atropine-administration in the same parts of GI tract. (3) The extent of cytoprotective effect of atropine against the IND was decreased after bilateral surgical vagotomy. CONCLUSIONS: (1) The IND causes microvascular endothel damage in the stomach and small intestinal. (2) The atropine has a cytoprotective effect in the stomach and small intestine against the aggressive effects of IND without decrease of gastric acid secretion. (3) The intact vagal nerve is necessary to the function of cytoprotective mechanisms of atropine against the IND.     

The effect of etodolac on bile salt and histamine-mediated gastric mucosal injury in the rat

The effect of the selective cyclo-oxygenase-type-2 (COX-2) inhibitor etodolac on gastric mucosal integrity and gastric acid secretion was investigated in the rat. Etodolac was given in doses comparable with those being used in man for therapy of rheumatic conditions. The effect of etodolac was studied in the presence of a mild barrier breaker and in the presence of increased rates of endogenous acid secretion. In conscious pylorus-ligated rats, etodolac given intragastrically in 16 or 32 mg /kg for 3 h did not by itself give rise to visible gastric mucosal injury. Etodolac, however, exacerbated gastric mucosal injury evoked by intragastric application of acidified sodium taurocholate (5 mM in 150 mM HCl) in a dose-dependent manner. This effect of edotolac was independent of changes in gastric acid secretory responses. In rats whose gastric acid secretion was stimulated by intraperitoneal histamine (5 mg/kg), and etodolac (given i.g. in doses of 16 or 32 mg/kg) also increased gastric mucosal injury caused by histamine dose-dependently in the 3-h pylorus-ligated rats. Etodolac decreased gastric mucus in the saline- and in the sodium taurocholate-treated rats. In urethane-anaesthetized acute gastric fistula rats, intragastric etodolac (32 mg/kg) did not modify basal gastric acid secretion. Our data suggest that etodolac, a selective COX-2 inhibitor, impairs gastric mucosal resistance and can exacerbate gastric mucosal injury caused by other mucosal barrier breaking agents. Cyclooxygenase type-2 thus contributes to the gastric mucosal defences.