FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy

Factor H-related protein 5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in the pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement, and follow-up data.A total of 120 patients with a histologically proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger sequencing, and selected variants were studied as recombinant proteins in ELISA and surface plasmon resonance (SPR).Eight exonic CFHR5 variations in 14 patients (12.6%) were observed. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period; furthermore, it showed clear association with signs of complement overactivation and clinically meaningful clusters.Our observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G

Comparison Evaluation of the Biological Effects of Sterigmatocystin and Aflatoxin B1 Utilizing SOS-Chromotest and a Novel Zebrafish (Danio rerio) Embryo Microinjection Method

Aflatoxin B1 (AFB1) is a potent mycotoxin and natural carcinogen. The primary producers of AFB1 are Aspergillus flavus and A. parasiticus. Sterigmatocystin (STC), another mycotoxin, shares its biosynthetic pathway with aflatoxins. While there are abundant data on the biological effects of AFB1, STC is not well characterised. According to published data, AFB1 is more harmful to biological systems than STC. It has been suggested that STC is about one-tenth as potent a mutagen as AFB1 as measured by the Ames test. In this research, the biological effects of S9 rat liver homogenate-activated and non-activated STC and AFB1 were compared using two different biomonitoring systems, SOS-Chromotest and a recently developed microinjection zebrafish embryo method. When comparing the treatments, activated STC caused the highest mortality and number of DNA strand breaks across all injected volumes. Based on the E. coli SOS-Chromotest, the two toxins exerted the same genotoxicities. Moreover, according to the newly developed zebrafish microinjection method, STC appeared more toxic than AFB1. The scarce information correlating AFB1 and STC toxicity suggests that AFB1 is a more potent genotoxin than STC. Our findings contradict this assumption and illustrate the need for more complex biomonitoring systems for mycotoxin risk assessment

Comparative investigation of the in vitro inhibitory potencies of 13-epimeric estrones and D-secoestrones towards 17β-hydroxysteroid dehydrogenase type 1

The inhibitory effects of 13-epimeric estrones, D-secooxime and D-secoalcohol estrone compounds on human placental 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated. The transformation of estrone to 17β-estradiol was studied by an in vitro radiosubstrate incubation method. 13α-Estrone inhibited the enzyme activity effectively with an IC50 value of 1.2 μM, which indicates that enzyme affinity is similar to that of the natural estrone substrate. The 13β derivatives and the compounds bearing a 3-hydroxy group generally exerted stronger inhibition than the 13α and 3-ether counterparts. The 3-hydroxy-13β-D-secoalcohol and the 3-hydroxy-13α-D-secooxime displayed an outstanding cofactor dependence, i.e. more efficient inhibition in the presence of NADH than NADPH. The 3-hydroxy-13β-D-secooxime has an IC50 value of 0.070 μM and is one of the most effective 17β-HSD1 inhibitors reported to date in the literature. © 2016 Informa UK Limited, trading as Taylor & Francis Group

ELTE EKSZ tartalmi feltárás (tárgyszavazás) szabályzata

Az ELTE EKSZ a tartalmi feltárás (tárgyszavazás) szabályzata a tárgyszavazás legfontosabb szabályait foglalja össze, nem tér ki minden lehetséges megoldásra. A szabályzat egyes pontjai részben ajánlások, melyektől a dokumentum tartalmának megfelelően el lehet térni. A sémák nem tartalmaznak minden lehetséges elemet, és a felsorolt elemek egy részének alkalmazása (a dőlt betűkkel szedett almezők) pedig fakultatív. A szabályzat ennek megfelelően rugalmasan alkalmazandó, viszont az azzal ellentmondásban álló megoldások alkalmazása tilos. A tárgyszavazás során a szabályzat mellett kötelező figyelembe venni az adatbázisban található korábbi megoldásokat, és – természetesen – az adott kiadvány tartalmát. A Részletes szabályok fejezetei az ETO jelzetek sorrendjében van felvéve. A szabályzathoz két melléklet tartozik: a Szinonimalista és a Fogalomtár. A Szinonimalista tartalmazza a már elfogadott szinonimákat, és utal azokra a kifejezésekre is, melyek jelentése hasonló, de nem szinonima, és a Fogalomtárban lettek felvéve

Synthesis and in vitro pharmacological evaluation of N-[(1-benzyl-1,2,3-triazol-4-yl)methyl]-carboxamides on d-secoestrone scaffolds

<p>An efficient synthesis of several <i>N</i>-[(1-benzyl-1,2,3-triazol-4-yl)methyl]carboxamides in the 13β- and 13α-d-secoestrone series is reported. Novel triazoles were synthesized via the Cu(I)-catalyzed azide–alkyne cycloaddition of steroidal alkynyl carboxamides and <i>p</i>-substituted benzyl azides. Each of the products was evaluated <i>in vitro</i> by means of MTT assays for antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF-7, A431 and A2780). Some of them exhibited activities similar to those of the reference agent cisplatin. On change of the substitution pattern of the benzyl group of the azide, great differences in the cell growth-inhibitory properties were observed. The <i>p</i>-alkylbenzyl-substituted triazoles selectively exerted high cytostatic action against A2780 cells, with IC₅₀ values of 1 µM. We investigated the potential inhibitory action exerted on the human 17β-HSD1 activity of the new secosteroids. Three triazoles effectively suppressed the estrone to 17β-estradiol conversion with IC₅₀ values in low micromolar range.</p

Comparative investigation of the <i>in vitro</i> inhibitory potencies of 13-epimeric estrones and D-secoestrones towards 17<b>β</b>-hydroxysteroid dehydrogenase type 1

<p>The inhibitory effects of 13-epimeric estrones, D-secooxime and D-secoalcohol estrone compounds on human placental 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated. The transformation of estrone to 17β-estradiol was studied by an <i>in vitro</i> radiosubstrate incubation method. 13α-Estrone inhibited the enzyme activity effectively with an IC₅₀ value of 1.2 μM, which indicates that enzyme affinity is similar to that of the natural estrone substrate. The 13β derivatives and the compounds bearing a 3-hydroxy group generally exerted stronger inhibition than the 13α and 3-ether counterparts. The 3-hydroxy-13β-D-secoalcohol and the 3-hydroxy-13α-D-secooxime displayed an outstanding cofactor dependence, i.e. more efficient inhibition in the presence of NADH than NADPH. The 3-hydroxy-13β-D-secooxime has an IC₅₀ value of 0.070 μM and is one of the most effective 17β-HSD1 inhibitors reported to date in the literature.</p