Hydrogen sulfide as an anti-calcification stratagem in human aortic valve: Altered biogenesis and mitochondrial metabolism of H2S lead to H2S deficiency in calcific aortic valve disease.

This is the final version. Available from Elsevier via the DOI in this record. Data availability: No data was used for the research described in the article.Hydrogen sulfide (H2S) was previously revealed to inhibit osteoblastic differentiation of valvular interstitial cells (VICs), a pathological feature in calcific aortic valve disease (CAVD). This study aimed to explore the metabolic control of H2S levels in human aortic valves. Lower levels of bioavailable H2S and higher levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected in aortic valves of CAVD patients compared to healthy individuals, accompanied by higher expression of cystathionine γ-lyase (CSE) and same expression of cystathionine β-synthase (CBS). Increased biogenesis of H2S by CSE was found in the aortic valves of CAVD patients which is supported by increased production of lanthionine. In accordance, healthy human aortic VICs mimic human pathology under calcifying conditions, as elevated CSE expression is associated with low levels of H2S. The expression of mitochondrial enzymes involved in H2S catabolism including sulfide quinone oxidoreductase (SQR), the key enzyme in mitochondrial H2S oxidation, persulfide dioxygenase (ETHE1), sulfite oxidase (SO) and thiosulfate sulfurtransferase (TST) were up-regulated in calcific aortic valve tissues, and a similar expression pattern was observed in response to high phosphate levels in VICs. AP39, a mitochondria-targeting H2S donor, rescued VICs from an osteoblastic phenotype switch and reduced the expression of IL-1β and TNF-α in VICs. Both pro-inflammatory cytokines aggravated calcification and osteoblastic differentiation of VICs derived from the calcific aortic valves. In contrast, IL-1β and TNF-α provided an early and transient inhibition of VICs calcification and osteoblastic differentiation in healthy cells and that effect was lost as H2S levels decreased. The benefit was mediated via CSE induction and H2S generation. We conclude that decreased levels of bioavailable H2S in human calcific aortic valves result from an increased H2S metabolism that facilitates the development of CAVD. CSE/H2S represent a pathway that reverses the action of calcifying stimuli.Eotvos Lorand Research NetworkHungarian GovernmentEuropean Union and the European Social FundEuropean Union and the European Social FundMinistry of Innovation and Technology of Hungary from the National Research, Development and Innovation FundMinistry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fun

Excitation function measurement for zirconium-89 and niobium-90 production using alpha-induced reactions on yttrium-89

An experiment of α-induced reactions on yttrium-89 was performed to investigate the excitation functions of 89Zr and 90Nb, which are suitable for immuno-PET studies. The stacked-foil method, activation technique, and off-line γ-ray spectrometry were used for this investigation. The excitation functions of 92m,91m,89m,89gNb,88Zr, and 90m,88g,87m,87gY were also derived and compared with earlier experimental and the TENDL-2017 data. Good agreements with part of the previous studies were found

Excitation functions for production of medically relevant radioisotopes in deuteron irradiations of Pr and Tm targets

Activation cross sections of deuteron induced reaction on monoisotopic Tm (Tm-169) and Pr (Pr-141) were measured by stacked foil experiments. First measurements are presented for direct or cumulative production of Nd-141, Nd-140, Nd-139m, Pr-142, Ce-139, Ce-137m and La-140. Thick target yields and practical batch activity are derived from the fitted excitation curves for the medically relevant Nd-140 and Pr-139 (as decay product of Nd-139m). For reactions on Tm targets previous published results up to 20 MeV are extended and confirmed up to 40 MeV for Yb-169, Tm-167,Tm-168 while high energy values are presented for the first time for Yb-166. Values for the thick target yield (TTY) of Yb-169 production are derived and the discussion of different production routes is in agreement with previous published results. A comparison of experimental values with different model codes shows that the upgraded versions of the ALICE and EMPIRE codes can give a better description of (d,pxn) reaction than older ones. (C) 2009 Elsevier B.V. All rights reserved

Which mechanism(s) for the (d,p) reactions? Or can the CDCC approach be used to compute transfer cross sections?

We propose to use the Continuum Discretized Coupled Channels approach to describe both the differential cross sections and the excitation fonctions for the (d,p) reactions