A méhüreg anatómiai rendellenességei habituális vetélőkben

Absztrakt Bevezetés: A habituális vetélés a nők 1%-át érintő rendellenesség, amelynek hátterében genetikai, endokrin, méhűri anatómiai, immunológiai, mikrobiológiai és hematológiai, valamint andrológiai zavarok mutathatók ki mint kockázati tényezők, de az esetek felében ismeretlen ok miatt alakul ki. Célkitűzés: A habituális vetélés kockázati tényezőinek kutatása során a szerzők arra a kérdésre kerestek választ, vajon a magyar lakosságban milyen gyakran fordul elő a méhüreget érintő anatómiai rendellenesség. Módszer: Retrospektív módon dolgozták fel 152 habituális vetélő adatait. Az esetleges méhűri eltérés tisztázására 132 betegben vagy diagnosztikus hiszteroszkópia, vagy a méhüreg 3 dimenziós ultrahangvizsgálata, 16 esetben hysterosalpingographia, 4 esetben hysterosalpingo-sonographia történt. Eredmények: Megállapították, hogy a habituális vetélők 15,8%-ában méhűri rendellenesség mutatható ki. A rendellenességek közül septum uteri 6,5%-ban, endometriumpolypus 2,6%-ban, uterus arcuatus 2%-ban, uterus bicornis 2%-ban, submucosus myomagöb 1,3%-ban és méhűri synechiák 1,3%-ban fordultak elő. Következtetések: A szerzők megfigyelése arra utal, hogy habituális vetélésben szenvedő nőkben a méhüreg morfológiai rendellenessége gyakori. Ilyen esetekben javasolt a méhüreg anatómiai vizsgálata. Orv. Hetil., 2015, 156(27), 1081–1084

Cellular FXIII in Human Macrophage-Derived Foam Cells

Funding Information: The research was funded by grants from the National Research, Development, and Innovation Office (NKFIH) (K129287), by the GINOP 2.3.2-15-2016-00050 project co-financed by the European Union and the European Regional Development Fund, and by the Hungarian Academy of Science (11014 project). J.B. and D.P. were supported by Eötvös Loránd Research Network (11003). The work was also supported by the University of Aberdeen Development Trust and by project grants from Friend of Anchor (RS2015 006), the British Heart Foundation (PG/15/82/31721), and a British Heart Foundation Fellowship (FS/11/2/28579) awarded to N.J.M. Publisher Copyright: © 2023 by the authors.Peer reviewedPublisher PD

Zinc Inhibits HIF-Prolyl Hydroxylase Inhibitor-Aggravated VSMC Calcification Induced by High Phosphate

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Hydrogen Sulfide Abrogates Hemoglobin-Lipid Interaction In Atherosclerotic Lesion

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Hydrogen Sulfide Abrogates Hemoglobin-Lipid Interaction in Atherosclerotic Lesion

This is the final version of the article. Available from Hindawi Publishing Corporation via the DOI in this record.The infiltration of red blood cells into atheromatous plaques is implicated in atherogenesis. Inside the lesion, hemoglobin (Hb) is oxidized to ferri-and ferrylHb which exhibit prooxidant and proinflammatory activities. Cystathione gamma-lyase-(CSE-) derived H 2 S has been suggested to possess various antiatherogenic actions. Expression of CSE was upregulated predominantly in macrophages, foam cells, and myofibroblasts of human atherosclerotic lesions derived from carotid artery specimens of patients. A similar pattern was observed in aortic lesions of apolipoprotein E-deficient mice on high-fat diet. We identified several triggers for inducing CSE expression in macrophages and vascular smooth muscle cells including heme, ferrylHb, plaque lipids, oxidized low-density lipoprotein, tumor necrosis factor-α, and interleukin-1β. In the interplay between hemoglobin and atheroma lipids, H 2 S significantly mitigated oxidation of Hb preventing the formation of ferrylHb derivatives, therefore providing a novel function as a heme-redox-intermediate-scavenging antioxidant. By inhibiting Hb-lipid interactions, sulfide lowered oxidized Hb-mediated induction of adhesion molecules in endothelium and disruption of endothelial integrity. Exogenous H 2 S inhibited heme and Hb-mediated lipid oxidation of human atheroma-derived lipid and human complicated lesion. Our study suggests that the CSE/H 2 S system represents an atheroprotective pathway for removing or limiting the formation of oxidized Hb and lipid derivatives in the atherosclerotic plaque.The research group is supported by the Hungarian Academy of Sciences (11003). This work was supported by Hungarian Government Grants (OTKA) K112333 (József Balla), K109843 (Péter Nagy), and K116024 (Viktória Jeney) and Marie Curie International Reintegration Grant PIRG08-GA-2010-277006 (Péter Nagy). Péter Nagy is a János Bolyai Research Scholar of the Hungarian Academy of Sciences. Viktória Jeney was supported by Zoltán Magyary Fellowship (TÁMOP 4.2.4.A/2-11/1-2012-0001). László Potor was supported by János Apáczai-Csere Fellowship (TÁMOP 4.2.4.A/2-11/1-2012-0001). The project was cofinanced by the European Union and the European Social Fund (ESF) GINOP-2.3.2-15-2016-00043 IRONHEARTH and EFOP-3.6.2-16-2017-00006 LIVE LONGER

Hydrogen Sulfide Abrogates Hemoglobin-Lipid Interaction In Atherosclerotic Lesion

The infiltration of red blood cells into atheromatous plaques is implicated in atherogenesis. Inside the lesion hemoglobin (Hb) is oxidized to ferri- and ferrylHb which exhibit pro-oxidant and pro-inflammatory activities. Cystathione-gamma lyase (CSE)-derived H2S has been suggested to possess various anti-atherogenic actions.Expression of CSE was upregulated predominantly in macrophages, foam cells and myofibroblasts of human atherosclerotic lesions derived from carotid artery specimens of patients. Similar pattern was observed in aortic lesions of apolipoprotein E deficient mice on high-fat diet. We identified several triggers for inducing CSE expression in macrophages and vascular smooth muscle cells including heme, ferrylHb, plaque lipids, oxidized low-density lipoprotein, tumor necrosis factor-? and interleukin-1?. In the interplay between hemoglobin and atheroma lipids, H2S significantly mitigated oxidation of Hb preventing the formation of ferrylHb derivatives, therefore providing a novel function as a heme-redox-intermediate-scavenging antioxidant. By inhibiting Hb-lipid interactions sulfide lowered oxidized Hb-mediated induction of adhesion molecules in endothelium and disruption of endothelial integrity. Exogenous H2S inhibited heme and Hb-mediated lipid oxidation of human atheroma derived lipid and human complicated lesion.Our study suggests that the CSE/H2S system represents an atheroprotective pathway for removing or limiting the formation of oxidized Hb and lipid derivatives in the atherosclerotic plaque

Heme Induces Endoplasmic Reticulum Stress (HIER Stress) in Human Aortic Smooth Muscle Cells

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Heme Induces Endoplasmic Reticulum Stress (HIER Stress) in Human Aortic Smooth Muscle Cells

Accumulation of damaged or misfolded proteins resulted from oxidative protein modification induces endoplasmic reticulum (ER) stress by activating the pathways of unfolded protein response. In pathologic hemolytic conditions, extracellular free hemoglobin is submitted to rapid oxidation causing heme release. Resident cells of atherosclerotic lesions, after intraplaque hemorrhage, are exposed to heme leading to oxidative injury. Therefore, we raised the question whether heme can also provoke ER stress. Smooth muscle cells are one of the key players of atherogenesis; thus, human aortic smooth muscle cells (HAoSMCs) were selected as a model cell to reveal the possible link between heme and ER stress. Using immunoblotting, quantitative polymerase chain reaction and immunocytochemistry, we quantitated the markers of ER stress. These were: phosphorylated eIF2α, Activating transcription factor-4 (ATF4), DNA-damage-inducible transcript 3 (also known as C/EBP homology protein, termed CHOP), X-box binding protein-1 (XBP1), Activating transcription factor-6 (ATF6), GRP78 (glucose-regulated protein, 78kDa) and heme responsive genes heme oxygenase-1 and ferritin. In addition, immunohistochemistry was performed on human carotid artery specimens from patients who had undergone carotid endarterectomy. We demonstrate that heme increases the phosphorylation of eiF2α in HAoSMCs and the expression of ATF4. Heme also enhances the splicing of XBP1 and the proteolytic cleavage of ATF6. Consequently, there is up-regulation of target genes increasing both mRNA and protein levels of CHOP and GRP78. However, TGFβ and collagen type I decreased. When the heme binding proteins, alpha-1-microglobulin (A1M) and hemopexin (Hpx) are present in cell media, the ER stress provoked by heme is inhibited. ER stress pathways are also retarded by the antioxidant N-acetyl cysteine (NAC) indicating that reactive oxygen species are involved in heme-induced ER stress. Consistent with these findings, elevated expression of the ER stress marker GRP78 and CHOP were observed in smooth muscle cells of complicated lesions with hemorrhage compared to either atheromas or healthy arteries. In conclusion, heme triggers ER stress in a time- and dose-dependent manner in HAoSMCs. A1M and Hpx as well as NAC effectively hamper heme-induced ER stress, supporting their use as a potential therapeutic approach to reverse such a deleterious effects of heme toxicity

A kén-hidrogén donor molekulák gátolják az alacsony sűrűségű lipoprotein oxidációját

A Vaszkuláris Biológiai Kutatócsoport 9 éve foglalkozik korunk egyik legszámottevőbb népbetegséggel az atherosclerosissal. Kimutatták, hogy a NaHS gátolja a hem mediálta LDL oxidatív modifikációját és a vaszkuláris simaizomsejtek kalcifikációját, illetve oszteoblasztos transzformációját(15,21).Számos olyan publikáció látott napvilágot mely megalapozza a kén-hidrogén élettanilag pozitív illetve anti-atherogén hatását. Munkám célja annak a felderítése, hogy bizonyos kén-hidrogén analóg és donorként szolgáló molekulák képesek-e, illetve milyen mértékben gátolják az alacsonysűrűségű lipoprotein (LDL) oxidációját, és a plakk bevérzést követően fellépő hemoglobin-lipid interakciókat.MSc/MABiotechnológiag

A hem-vas szerepe a simaizomsejtek kalcifikációjában

A hem számos tekintetben a vashoz hasonló reakciókat vált ki, így feltételeztük, hogy a hem a vashoz hasonlóan gátolni fogja a vaszkuláris simaizomsejtek foszfát-mediálta kalcifikációját és oszteoblasztos transzformációját.BscBiológiag