Acido solfidrico nella letteratura internazionale Studi inseriti in PubMed nel mese di ottobre 2016

(aggiornamento 16 novembre 2016)

(1) Le PP, Battaglia-Brunet F, Parmentier M, Joulian C, Gassaud C, Fernandez-Rojo L, et al. Complete removal of arsenic and zinc from a heavily contaminated acid mine drainage via an indigenous SRB consortium. J Hazard Mater 2017 Jan 5;321:764-72. Abstract: Acid mine drainages (AMD) are major sources of pollution to the environment. Passive bio-remediation technologies involving sulfate-reducing bacteria (SRB) are promising for treating arsenic contaminated waters. However, mechanisms of biogenic As-sulfide formation need to be better understood to decontaminate AMDs in acidic conditions. Here, we show that a high-As AMD effluent can be decontaminated by an indigenous SRB consortium. AMD water from the Carnoules mine (Gard, France) was incubated with the consortium under anoxic conditions and As, Zn and Fe concentrations, pH and microbial activity were monitored during 94days. Precipitated solids were analyzed using electron microscopy (SEM/TEM-EDXS), and Extended X-Ray Absorption Fine Structure (EXAFS) spectroscopy at the As K-edge. Total removal of arsenic and zinc from solution (1.06 and 0.23mmol/L, respectively) was observed in two of the triplicates. While Zn precipitated as ZnS nanoparticles, As precipitated as amorphous orpiment (am-AsIII2S3) (33-73%), and realgar (AsIIS) (0-34%), the latter phase exhibiting a particular nanowire morphology. A minor fraction of As is also found as thiol-bound AsIII (14-23%). We propose that the formation of the AsIIS nanowires results from AsIII2S3 reduction by biogenic H2S, enhancing the efficiency of As removal. The present description of As immobilization may help to set the basis for bioremediation strategies using SRB

(2) Jiang Z, Hua Y. Hydrogen sulfide promotes osteogenic differentiation of human periodontal ligament cells via p38-MAPK signaling pathway under proper tension stimulation. Arch Oral Biol 2016 Dec;72:8-13. Abstract: OBJECTIVE: Hydrogen sulfide (H2S), one of endogenous gaseous signalling molecules, can be induced by mechanical force stimulation on human periodontal ligament cells (hPDLCs). Little is known about the mechanism of H2S on the osteogenic differentiation although previous studies have demonstrated that H2S stimulated or inhibited osteoclastic differentiation. The present study was to investigate whether H2S played a regulatory role in osteogenic differentiation of the periodontal tissue remodeling and the involvement of mitogen-activated protein kinase (MAPK) signaling in this process. DESIGN: hPDLCs were applied with cycle tension force for 6h, 12h, 24h or 48h to select the optimal time for force application. Then the effects of H2S on hPDLCs osteogenic differentiation were investigated. Signal-regulated kinases p38-MAPK and ERK activities with H2S treatment were measured. Finally, specific MAPK inhibitors SB203580 and U0126 were employed to investigate the involvement of the two kinases in hPDLCs osteogenic differentiation with H2S pre-treatment. RESULTS: Tension stimulation promoted mRNA and protein expression of ALP, OCN and Runx2 in hPDLCs. The expression of ALP, OCN and Runx2 increased in a concentration-dependent manner with H2S pre-treatment. Importantly, p38-MAPK and ERK were activated in different ways upon induction by H2S. Furthermore, expression of Runx2, ALP and OCN, the osteogenic regulators, was reversed by SB203580 and U0126. CONCLUSIONS: H2S could promote osteogenic differentiation of hPDLCs by activating p38-MAPK and ERK signaling pathways

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(3) D'Imprima E, Mills DJ, Parey K, Brandt U, Kuhlbrandt W, Zickermann V, et al. Cryo-EM structure of respiratory complex I reveals a link to mitochondrial sulfur metabolism. Biochim Biophys Acta 2016 Dec;1857(12):1935-42. Abstract: Mitochondrial complex I is a 1MDa membrane protein complex with a central role in aerobic energy metabolism. The bioenergetic core functions are executed by 14 central subunits that are conserved from bacteria to man. Despite recent progress in structure determination, our understanding of the function of the ~30 accessory subunits associated with the mitochondrial complex is still limited. We have investigated the structure of complex I from the aerobic yeast Yarrowia lipolytica by cryo-electron microscopy. Our density map at 7.9A resolution closely matches the 3.6-3.9A X-ray structure of the Yarrowia lipolytica complex. However, the cryo-EM map indicated an additional subunit on the side of the matrix arm above the membrane surface, pointing away from the membrane arm. The density, which is not present in any previously described complex I structure and occurs in about 20 % of the particles, was identified as the accessory sulfur transferase subunit ST1. The Yarrowia lipolytica complex I preparation is active in generating H2S from the cysteine derivative 3-mercaptopyruvate, catalyzed by ST1. We thus provide evidence for a link between respiratory complex I and mitochondrial sulfur metabolism

(4) Lin S, Visram F, Liu W, Haig A, Jiang J, Mok A, et al. GYY4137, a Slow-Releasing Hydrogen Sulfide Donor, Ameliorates Renal Damage Associated with Chronic Obstructive Uropathy. J Urol 2016 Dec;196(6):1778-87. Abstract: PURPOSE: Chronic obstructive uropathy can cause irreversible kidney injury, atrophy and inflammation, which can ultimately lead to fibrosis. Epithelial-mesenchymal transition is a key trigger of fibrosis that is caused by up-regulation of TGF-beta1 (transforming growth factor-beta1) and ANGII (angiotensin II). H2S is an endogenously produced gasotransmitter with cytoprotective properties. We sought to elucidate the effects of the slow-releasing H2S donor GYY4137 on chronic ureteral obstruction and evaluate the potential mechanisms. MATERIALS AND METHODS: Following unilateral ureteral obstruction male Lewis rats were given daily intraperitoneal administration of phosphate buffered saline vehicle (obstruction group) or phosphate buffered saline plus 200 mumol/kg GYY4137 (obstruction plus GYY4137 group) for 30 days. Urine and serum samples were collected to determine physiological parameters of renal function and injury. Kidneys were removed on postoperative day 30 to evaluate histopathology and protein expression. Epithelial-mesenchymal transition in LLC-PK1 pig kidney epithelial cells was induced with TGF-beta1 and treated with GYY4137 to evaluate potential mechanisms via in vitro scratch wound assays. RESULTS: H2S treatment decreased serum creatinine and the urine protein-to-creatinine excretion ratio after unilateral ureteral obstruction. In addition, H2S mitigated cortical loss, inflammatory damage and tubulointerstitial fibrosis. Tissues showed decreased expression of epithelial-mesenchymal transition markers upon H2S treatment. Epithelial-mesenchymal transition progression in LLC-PK1 was alleviated upon in vitro administration of GYY4137. CONCLUSIONS: To our knowledge our findings demonstrate for the first time the protective effects of H2S in chronic obstructive uropathy. This may represent a potential therapeutic solution to ameliorate renal damage and improve the clinical outcomes of urinary obstruction

(5) Guo Y, Gong M, Li Y, Liu Y, Dou X. Sensitive, Selective, and Fast Detection of ppb-Level H2S Gas Boosted by ZnO-CuO Mesocrystal. Nanoscale Res Lett 2016 Dec;11(1):475. Abstract: ZnO-CuO mesocrystal was prepared via topotactic transformation using one-step direct annealing of aqueous precursor solution and assembled into a H2S sensor. The ZnO-CuO mesocrystal-based sensor possesses good linearity and high sensitivity in the low-concentration range (10-200 ppb). Compared to pure CuO, the as-prepared ZnO-CuO mesocrystal sensor exhibited superior H2S sensing performance with a response ranging from 8.6 to 152 % towards H2S concentrations from 10 ppb to 10 ppm when applied at the optimized working temperature of 125 degrees C. The sensor showed

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excellent repeatability and good selectivity towards H2S gas even at a concentration four orders of magnitude lower than the interfering gases, such as H2, CO2, CO, NO2, acetone, and NH3. The improved sensitivity could be attributed partially to the effective diffusion of analyte gas through the mesocrystal surface and the abundant accessible active sites. Moreover, the nanoscale p-n junctions within the mesocrystal, which could effectively manipulate the local charge carrier concentration, are also beneficial to boost the sensing performance

(6) Kara H, Isli F, Ozturk Fincan GS, Yildirim S, Ercan S, Sarioglu Y. The effects of hydrogen sulfide on electrical field stimulation-induced neurogenic contractile responses in isolated rabbit lower esophageal sphincter: Contribution of nitrergic and non-adrenergic non-cholinergic transmission. Pharmacol Rep 2016 Dec;68(6):1350-7. Abstract: BACKGROUND: Hydrogen sulfide (H2S) is a gaseous signaling molecule that, similar to nitric oxide (NO), plays an important role as an inhibitor neurotransmitter in the digestive tract. This study aimed to investigate the effect of H2S and to identify neurogenic contraction responses dependent on the electrical field stimulation (EFS) in the isolated lower esophageal sphincters of rabbits. METHODS: An isolated lower esophageal sphincter was placed in an organ bath system and mechanical responses were recorded using a force transducer. The nerve-evoked contractile responses were obtained by EFS. The contractile responses were obtained as biphasic "on" and "off" phases seen at the beginning and end of EFS, respectively. RESULTS: Sodium hydrogen sulfide (NaHS) reduced the EFS-mediated "off" phase and the EFS-mediated non-adrenergic non-cholinergic (NANC) "off" phase. NaHS reduced the EFS-mediated "on" phase as well. l-Cysteine reduced the EFS-mediated "off" phase and the EFS-mediated NANC "off" phase. l-Propargylglycine (PAG) did not affect the EFS-mediated "off" phase or the EFS-mediated NANC "off" phase. NaHS, l-cysteine, and PAG reduced the EFS-mediated, NO-independent "off" phase. The effect of NaHS in all of the experiments returned in time. Also, NaHS caused significant relaxation of 80-mM KCl-Krebs solution induced-contractions, while l-cysteine and PAG did not cause a significant relaxation. CONCLUSION: These findings suggest that H2S has an inhibitory effect on the lower esophageal sphincter muscle. While the effect of H2S on EFS-mediated responses disappeared in time, the effect of H2S sustained the KCl-Krebs solution-induced contractions. This shows that H2S may have an effect on neurotransmission at the nerve terminal

(7) Wu WJ, Jia WW, Liu XH, Pan LL, Zhang QY, Yang D, et al. S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathway. Redox Biol 2016 Dec;10:157-67. Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Hydrogen sulfide (H2S), the third physiological gasotransmitter, is well recognized as an anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the protective effects of S-propargyl-cysteine (SPRC, also known as ZYZ-802), an endogenous H2S modulator, on RA and determined the underlying mechanisms. In the present study, SPRC concentration-dependently attenuated inflammatory mediator expression, reactive oxidase species generation, and the expression and activity of matrix metalloproteinases (MMP)-9 in interleukin (IL)-1beta-induced human rheumatoid fibroblast-like synoviocytes MH7A. In addition, SPRC blocked IL-1beta-mediated migration and invasion of MH7A cells. As expected, the protective effects of SPRC were partially abrogated by DL-propargylglycine (PAG, a H2S biosynthesis inhibitor). In vivo study also demonstrated that SPRC treatment markedly ameliorated the severity of RA in adjuvant-induced arthritis rats, and this effect was associated with the inhibition of inflammatory response. We further identified that SPRC remarkably induced heme oxygenase-1 expression associated with the degradation of Kelch-like ECH-associated protein 1 (Keap1) and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2); this effect was attributed to the sulfhydrylation of the cysteine residue of Keap1. Our data demonstrated for the first time that SPRC, an endogenous H2S modulator,

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exerted anti-inflammatory properties in RA by upregulating the Nrf2-antioxidant response element (ARE) signaling pathway

(8) Curren J, Hallis SA, Snyder CC, Suffet IM. Identification and quantification of nuisance odors at a trash transfer station. Waste Manag 2016 Dec;58:52-61. Abstract: The objective of this study was to evaluate the effectiveness of a modified Odor Profile Method (OPM) at a trash transfer station (TTS). An updated Landfill Odor Wheel was used to define odor character and distinguish among odor sources. The Flavor Profile Analysis (FPA) intensity scale was used to rank the relative intensity of the various odor characters defined by the odor wheel and to understand how each odor profile changed off site. Finally, the odor wheel was used to select the appropriate chemical analysis to identify the odorants causing the odors identified by the human panelists. The OPM was demonstrated as an effective tool for characterizing and distinguishing odor sources at a TTS. Municipal solid waste (MSW) odors were characterized as rancid, sulfur, and fragrant; rancid odors were dominant in the odor profile on-site, while sulfur odors dominated off-site. Targeted chemical analysis was used to identify odorants potentially responsible for odors at the site. Methyl mercaptan (rotten vegetable) and hydrogen sulfide (rotten egg) were identified as the odorants most likely to be responsible for the sulfur odors at the site. Acetaldehyde (sweet, fruity), acetic acid (vinegar), and butyric acid (rancid) were identified as the odorants mostly likely to be causing the rancid and sour odors. Terpenes/pine odors were observed near the greenwaste pile. Results confirm that the OPM, together with properly selected chemical analyses, can be a useful tool for identifying and quantifying the sources of odors

(9) Hennebert P, Samaali I, Molina P. A proposal for a test method for assessment of hazard property HP 12 ("Release of an acute toxic gas") in hazardous waste classification - Experience from 49 waste. Waste Manag 2016 Dec;58:25-33. Abstract: A stepwise method for assessment of the HP 12 is proposed and tested with 49 waste samples. The hazard property HP 12 is defined as "Release of an acute toxic gas": waste which releases acute toxic gases (Acute Tox. 1, 2 or 3) in contact with water or an acid. When a waste contains a substance assigned to one of the following supplemental hazards EUH029, EUH031 and EUH032, it shall be classified as hazardous by HP 12 according to test methods or guidelines (EC, 2014a, 2014b). When the substances with the cited hazard statement codes react with water or an acid, they can release HCl, Cl2, HF, HCN, PH3, H2S, SO2 (and two other gases very unlikely to be emitted, hydrazoic acid HN3 and selenium oxide SeO2 - a solid with low vapor pressure). Hence, a method is proposed:For a set of 49 waste, water addition did not produce gas. Nearly all the solid waste produced a gas in contact with hydrochloric acid in 5 min in an automated calcimeter with a volume >0.1L of gas per kg of waste. Since a plateau of pressure is reached only for half of the samples in 5 min, 6 h trial with calorimetric bombs or glass flasks were done and confirmed the results. Identification of the gases by portable probes showed that most of the tested samples emit mainly CO2. Toxic gases are emitted by four waste: metallic dust from the aluminum industry (CO), two air pollution control residue of industrial waste incinerator (H2S) and a halogenated solvent (organic volatile(s) compound(s)). HF has not been measured in these trials started before the present definition of HP 12. According to the definition of HP 12, only the H2S emission of substances with hazard statement EUH031 is accounted for. In view of the calcium content of the two air pollution control residue, the presence of calcium sulphide (EUH031) can be assumed. These two waste are therefore classified potentially hazardous for HP 12, from a total of 49 waste. They are also classified as hazardous for other properties (HP 7, 10and14 for one of them, and HP 10and14 for the other one respectively). Given these results, it can be assumed that few common household and industrial waste will be classified hazardous only by HP 12

(10) Pedros PB, Askari O, Metghalchi H. Reduction of nitrous oxide emissions from biological nutrient removal processes by thermal decomposition. Water Res 2016 Dec 1;106:304-

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11. Abstract: During the last decade municipal wastewater treatment plants have been regulated with increasingly stringent nutrient removal requirements including nitrogen. Typically biological treatment processes are employed to meet these limits. Although the nitrogen in the wastewater stream is reduced, certain steps in the biological processes allow for the release of gaseous nitrous oxide (N2O), a greenhouse gas (GHG). A comprehensive study was conducted to investigate the potential to mitigate N2O emissions from biological nutrient removal (BNR) processes by means of thermal decomposition. The study examined using the off gases from the biological process, instead of ambient air, as the oxidant gas for the combustion of biomethane. A detailed analysis was done to examine the concentration of N2O and 58 other gases that exited the combustion process. The analysis was based on the assumption that the exhaust gases were in chemical equilibrium since the residence time in the combustor is sufficiently longer than the chemical characteristics. For all inlet N2O concentrations the outlet concentrations were close to zero. Additionally, the emission of hydrogen sulfide (H2S) and ten commonly occurring volatile organic compounds (VOCs) were also examined as a means of odor control for biological secondary treatment processes or as potential emissions from an anaerobic reactor of a BNR process. The sulfur released from the H2S formed sulfur dioxide (SO2) and eight of the ten VOCs were destroyed

(11) Tomasova L, Dobrowolski L, Jurkowska H, Wrobel M, Huc T, Ondrias K, et al. Intracolonic hydrogen sulfide lowers blood pressure in rats. Nitric Oxide 2016 Nov 30;60:50-8. Abstract: Research suggests that hydrogen sulfide (H2S) is an important biological mediator involved in various physiological processes including the regulation of arterial blood pressure (BP). Although H2S is abundant in the colon, the effects of gut-derived H2S on the circulatory system have not yet been investigated. We studied the effects of intracolonic administration of Na2S, a H2S donor, on systemic hemodynamics. Hemodynamics were recorded in anesthetized, normotensive Wistar Kyoto and spontaneously hypertensive rats at baseline and after intracolonic injection of either saline (controls) or Na2S.9H2O saline solution at a dose range of 10-300 mg/kg of BW. The H2S donor produced a significant, dose-dependent decrease in mean arterial blood pressure (MABP), which lasted several times longer than previously reported after parenteral infusions (>90 min). The effect was more pronounced in hypertensive than in normotensive rats. The Na2S-induced decrease in MABP was reduced by pretreatment with glibenclamide, an inhibitor of ATP-sensitive potassium-channels. Na2S did not affect mesenteric vein blood flow. Rats treated with Na2S showed increased portal blood levels of thiosulfate and sulfane sulfur, products of H2S oxidation. In contrast, rats treated with neomycin, an antibiotic, showed significantly decreased levels of thiosulfate and sulfane sulfur, and a tendency for greater hypotensive response to Na2S. The H2S donor decreased heart rate but did not affect ECG morphology and QTc interval. In conclusion the gut-derived H2S may contribute to the control of BP and may be one of the links between gut microbiota and hypertension. Furthermore, gut-derived H2S may be a therapeutic target in hypertension

(12) Tain YL, Lee CT, Chan JY, Hsu CN. Maternal melatonin or N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and renal transcriptome to prevent prenatal NG-Nitro-L-arginine-methyl ester (L-NAME)-induced fetal programming of hypertension in adult male offspring. Am J Obstet Gynecol 2016 Nov;215(5):636. Abstract: BACKGROUND: Pregnancy is a critical time for fetal programming of hypertension. Nitric oxide deficiency during pregnancy causes hypertension in adult offspring. OBJECTIVE: We examined whether maternal melatonin or N-acetylcysteine therapy can prevent NG-nitro-L-arginine-methyl ester-induced fetal programming of hypertension in adult offspring. Next, we aimed to identify potential gatekeeper pathways that contribute to NG-nitro-L-arginine-methyl ester -induced programmed hypertension using the next generation RNA sequencing technology. STUDY DESIGN: Pregnant

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Sprague-Dawley rats were assigned to 4 groups: control, NG-nitro-L-arginine-methyl ester, NG-nitro-L-arginine-methyl ester +melatonin, and NG-nitro-L-arginine-methyl ester+N-acetylcysteine. Pregnant rats received NG-nitro-L-arginine-methyl ester administration at 60 mg/kg/d subcutaneously during pregnancy alone, with additional 0.01% melatonin in drinking water, or with additional 1% N-acetylcysteine in drinking water during the entire pregnancy and lactation. Male offspring (n=8/group) were killed at 12 weeks of age. RESULTS: NG-nitro-L-arginine-methyl ester exposure during pregnancy induced programmed hypertension in adult male offspring, which was prevented by maternal melatonin or N-acetylcysteine therapy. Protective effects of melatonin and N-acetylcysteine against NG-nitro-L-arginine-methyl ester-induced programmed hypertension were associated with an increase in hydrogen sulfide-generating enzymes and hydrogen sulfide synthesis in the kidneys. Nitric oxide inhibition by NG-nitro-L-arginine-methyl ester in pregnancy caused >2000 renal transcripts to be modified during nephrogenesis stage in 1-day-old offspring kidney. Among them, genes belong to the renin-angiotensin system, and arachidonic acid metabolism pathways were potentially involved in the NG-nitro-L-arginine-methyl ester-induced programmed hypertension. However, melatonin and N-acetylcysteine reprogrammed the renin-angiotensin system and arachidonic acid pathway differentially. CONCLUSION: Our results indicated that antioxidant therapy, by melatonin or N-acetylcysteine, in pregnant rats with nitric oxide deficiency can prevent programmed hypertension in male adult offspring. Early intervention with specific antioxidants that target redox imbalance in pregnancy to reprogram hypertension may well allow us to reduce the future burden of hypertension. The roles of transcriptome changes that are induced by NG-nitro-L-arginine-methyl ester in the offspring kidney require further clarification

(13) Azrael D, Mukamal A, Cohen AP, Gunnell D, Barber C, Miller M. Identifying and Tracking Gas Suicides in the U.S. Using the National Violent Death Reporting System, 2005-2012. Am J Prev Med 2016 Nov;51(5S3):S219-S225. Abstract: INTRODUCTION: Identifying the source and specific type of gas used in suicides is difficult using most data systems owing to limitations in ICD-10 coding. The National Violent Death Reporting System (NVDRS), with its rich collection of both coded and free-text variables, has the potential to overcome these limitations. This study used a multipronged approach to identify gas-specific suicides in NVDRS and to track the incidence of these suicides over time. METHODS: Using suicide cases from the 16 NVDRS states that participated throughout 2005-2012, free-text and code searches were conducted for four types of variables-incident narratives, coroner/medical examiner cause-of-death statements, cause-of-death codes, and substance names-to identify suicides by carbon monoxide, helium, hydrogen sulfide, and four other gases. All analyses were conducted in 2015. RESULTS: Approximately 4% (3,242 of 80,715) of suicides recorded in NVDRS over the study period were the result of gas inhalation. Of these, the majority (73%) were carbon monoxide suicides (almost exclusively from motor vehicle exhaust and charcoal burning). Other types of gas (most notably helium), once rare, are now more common: At the start of the study period non-carbon monoxide gas suicides represented 15% of all gas suicides; at the end of the study period, they represented 40%. CONCLUSIONS: Public health policies to reduce a suicidal person's access to more lethal suicide methods require a reliable source of surveillance data on specific methods used in suicide. Small changes to NVDRS could make it an efficient and nimble surveillance system for tracking these deaths

(14) Feliers D, Lee HJ, Kasinath BS. Hydrogen Sulfide in Renal Physiology and Disease. Antioxid Redox Signal 2016 Nov 1;25(13):720-31. Abstract: SIGNIFICANCE: Hydrogen sulfide (H2S) has only recently gained recognition for its physiological effects. It is synthesized widely in the mammalian tissues and regulates several biologic processes ranging from development, angiogenesis, neurotransmission to protein synthesis. Recent Advances: The aim of this review is to critically evaluate the evidence for a role for H2S in kidney function and disease.

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CRITICAL ISSUES: H2S regulates fundamental kidney physiologic processes such as glomerular filtration and sodium reabsorption. In kidney disease states H2S appears to play a complex role in a context-dependent manner. In some disease states such as ischemia-reperfusion and diabetic kidney disease it can serve as an agent that ameliorates kidney injury. In other diseases such as cis-platinum-induced kidney disease it may mediate kidney injury although more investigation is needed. Recent studies have revealed that the actions of nitric oxide and H2S may be integrated in kidney cells. FUTURE DIRECTIONS: Further studies are needed to understand the full impact of H2S on kidney physiology. As it is endowed with the properties of regulating blood flow, oxidative stress, and inflammation, H2S should be investigated for its role in inflammatory and toxic diseases of the kidney. Such in-depth exploration may identify specific kidney diseases in which H2S may constitute a unique target for therapeutic intervention. Antioxid. Redox Signal. 25, 720-731

(15) Marino A, Martelli A, Citi V, Fu M, Wang R, Calderone V, et al. The novel H2 S donor 4-carboxy-phenyl isothiocyanate inhibits mast cell degranulation and renin release by decreasing intracellular calcium. Br J Pharmacol 2016 Nov;173(22):3222-34. Abstract: BACKGROUND AND PURPOSE: Hydrogen sulfide (H2 S) modulates many pathophysiological processes, including inflammation and allergic reactions, in which mast cells act as major effector cells. IgE receptor (FcepsilonRI) cross linking leads to an increase in intracellular calcium ([Ca+2 ]i ), a critical step in mast cell degranulation. The aim of this study was to investigate the role of H2 S in [Ca+2 ]i -dependent mast cell activation. EXPERIMENTAL APPROACH: We investigated the effects of H2 S, either endogenously produced or released by the slow H2 S donor 4-carboxy-phenyl isothiocyanate (PhNCS-COOH), on antigenic- and non-antigenic degranulation of native murine mast cells, and human and rat (RBL-2H3) mast cell lines. We measured the release of specific mast cell degranulation markers (beta-hexosaminidase and renin), as well as changes in [Ca+2 ]i and phosphorylation of proteins downstream of FcepsilonRI activation. KEY RESULTS: Endogenously produced H2 S inhibited antigen-induced degranulation in RBL-2H3. Similarly, H2 S released by PhNCS-COOH (10-300 muM) reduced, in a concentration-dependent manner, antigenic and non-antigenic degranulation and renin release in all mast cell types. Notably, PhNCS-COOH also prevented in a concentration-dependent mode the increase in [Ca+2 ]i elicited by Ca+2 ionophore, thapsigargin and FcepsilonRI activation. Moreover, PhNCS-COOH attenuated the phosphorylation of Syk, cPLA-2 and PLCgamma1 in antigen-stimulated RBL-2H3 cells. CONCLUSION AND IMPLICATIONS: Collectively, our results demonstrate that, by attenuating the phosphorylation of proteins downstream of FcepsilonRI cross-linking on mast cells, H2 S diminishes [Ca+2 ]i availability and thus mast cell degranulation and renin release. These findings suggest that PhNCS-COOH could be a strategic therapeutic tool in mast cell-mediated allergic conditions

(16) Lian X, Gollasch M. A Clinical Perspective: Contribution of Dysfunctional Perivascular Adipose Tissue (PVAT) to Cardiovascular Risk. Curr Hypertens Rep 2016 Nov;18(11):82. Abstract: Perivascular adipose tissue (PVAT) is now recognized as an important paracrine organ influencing the homeostasis of the vessel wall, regional blood flow and peripheral arterial resistance. There is remarkable phenotypic variability and plasticity of PVAT among various vascular beds, exhibiting phenotypes from white to brown and beige adipocytes. PVAT dysfunction is characterized by disturbed secretion of various adipokines, which, together with endothelial dysfunction, contribute to hypertension and cardiovascular disease (CVD). This brief review describes our current knowledge on PVAT in health and cardiovascular disease, with a special focus on different phenotypes and signaling pathways in adipocytes of PVAT associated with hypertension, obesity and cardiovascular disorders

(17) Schubert ML. Gastric acid secretion. Curr Opin Gastroenterol 2016 Nov;32(6):452-60. Abstract: PURPOSE OF REVIEW: The present review summarizes the past year's

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literature, both clinical and basic science, regarding neuroendocrine and intracellular regulation of gastric acid secretion and proper use of antisecretory medications. RECENT FINDINGS: Gastric acid kills microorganisms, modulates the gut microbiome, assists in digestion of protein, and facilitates absorption of iron, calcium, and vitamin B12. The main stimulants of acid secretion are gastrin, released from antral G cells; histamine, released from oxyntic enterochromaffin-like cells; and acetylcholine, released from antral and oxyntic intramural neurons. Other stimulants include ghrelin, motilin, and hydrogen sulfide. The main inhibitor of acid secretion is somatostatin, released from oxyntic and antral D cells. Glucagon-like peptide-1 also inhibits acid secretion. Proton pump inhibitors (PPIs) reduce acid secretion and, as a result, decrease somatostatin and thus stimulate gastrin secretion. Although considered well tolerated drugs, concerns have been raised this past year regarding associations between PPI use and kidney disease, dementia, and myocardial infarction; the quality of evidence, however, is very low. SUMMARY: Our understanding of the physiology of gastric secretion and proper use of PPIs continues to advance. Such knowledge is crucial for improved management of acid-peptic disorders

(18) Magierowski M, Magierowska K, Szmyd J, Surmiak M, Sliwowski Z, Kwiecien S, et al. Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised by Mild Stress Against Alendronate Injury. Dig Dis Sci 2016 Nov;61(11):3176-89. Abstract: BACKGROUND: Alendronate is an inhibitor of osteoclast-mediated bone resorption, but its clinical utility is limited due to gastrointestinal complications including bleeding erosions. AIMS: We studied whether potent vasodilators hydrogen sulfide (H2S) and carbon monoxide (CO) can protect against alendronate-induced gastric lesions in rats exposed to mild stress. METHODS: Three series (A, B, and C) of Wistar rats received alendronate (150-700 mg/kg i.g., series A) with or without NaHS (5 mg/kg), H2S donor or CORM-2 (5 mg/kg) releasing CO administered i.g. 30 min before alendronate administration (series B) in rats exposed for 3 days before alendronate administration to mild stress (series C). The area of gastric lesions was assessed by planimetry, the gastric blood flow (GBF) was determined by H2-gas clearance technique, and H2S production via CSE/CBS/3-MST activity and the gastric expression of HO-1, HO-2, HIF-1alpha, NF-kappaB, iNOS, COX-2, IL-1beta, TNF-alpha, GPx-1 and SOD-2 were analyzed by qPCR or Western blot. RESULTS: Alendronate dose-dependently produced gastric mucosal lesions and significantly decreased GBF, and these effects were exacerbated by mild stress. NaHS and CORM-2 significantly reduced the alendronate-induced gastric lesions in non-stressed and stressed animals, but only NaHS but not CORM-2 raised H2S production. NaHS and CORM-2 inhibited gastric expression of HIF-1alpha protein and HO-1, HIF-1alpha, NF-kappaB, COX-2, iNOS, IL-1beta, TNF-alpha mRNAs but failed to affect those of HO-2, GPx-1, and SOD-2. CONCLUSION: Both H2S and CO released from their donors, NaHS and CORM-2, protect gastric mucosa compromised by stress against alendronate-induced gastric damage via mechanism involving downregulation of HIF-1alpha, NF-kappaB and proinflammatory factors COX-2, iNOS, IL-1beta, and TNF-alpha

(19) Palomo A, Jane FS, Gulay A, Rasmussen S, Sicheritz-Ponten T, Smets BF. Metagenomic analysis of rapid gravity sand filter microbial communities suggests novel physiology of Nitrospira spp. ISME J 2016 Nov;10(11):2569-81. Abstract: Rapid gravity sand filtration is a drinking water production technology widely used around the world. Microbially catalyzed processes dominate the oxidative transformation of ammonia, reduced manganese and iron, methane and hydrogen sulfide, which may all be present at millimolar concentrations when groundwater is the source water. In this study, six metagenomes from various locations within a groundwater-fed rapid sand filter (RSF) were analyzed. The community gene catalog contained most genes of the nitrogen cycle, with particular abundance in genes of the nitrification pathway. Genes involved in different carbon fixation pathways were also abundant, with the reverse tricarboxylic acid cycle pathway most abundant, consistent with an observed Nitrospira dominance. From the metagenomic data set, 14 near-

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complete genomes were reconstructed and functionally characterized. On the basis of their genetic content, a metabolic and geochemical model was proposed. The organisms represented by draft genomes had the capability to oxidize ammonium, nitrite, hydrogen sulfide, methane, potentially iron and manganese as well as to assimilate organic compounds. A composite Nitrospira genome was recovered, and amo-containing Nitrospira genome contigs were identified. This finding, together with the high Nitrospira abundance, and the abundance of atypical amo and hao genes, suggests the potential for complete ammonium oxidation by Nitrospira, and a major role of Nitrospira in the investigated RSFs and potentially other nitrifying environments

(20) Huang Z, Dong X, Zhuang X, Hu X, Wang L, Liao X. Exogenous hydrogen sulfide protects against high glucoseinduced inflammation and cytotoxicity in H9c2 cardiac cells. Mol Med Rep 2016 Nov;14(5):4911-7. Abstract: Hyperglycemia serves an important role in the pathogenesis of diabetic cardiomyopathy. The aim of the present study was to investigate whether exogenous hydrogen sulfide (H2S) protects against high glucoseinduced inflammation and cytotoxicity in cardiac cells by inhibiting the p38 mitogenactivated protein kinase (MAPK)/nuclear factorkappaB (NFkappaB), cyclooxygenase2 (COX2) and inducible nitric oxide synthase (iNOS) signaling pathways. Rat H9c2 myocardium cells were exposed to 33 mM glucose (high glucose, HG) for 24 h to stimulate HGinduced cytotoxicity. One group of cells was pretreated with NaHS (a donor of H2S) prior to HG exposure, and cell viability was determined using the Cell Counting Kit8 assay. The protein expression levels of p38MAPK, the phosphorylated p65 subunit of NFkappaB, iNOS, COX2 and caspase3 were analyzed by western blotting, and the protein expression levels of interleukin (IL)1beta and IL6 were detected by enzymelinked immunosorbent assay (ELISA). Pretreatment of H9c2 cells with NaHS for 30 min prior to exposure to HG significantly ameliorated the expression of p38MAPK and NFkappaB. In addition, pretreatment with NaHS markedly attenuated p38MAPK/NFkappaBmediated cytotoxicity and inflammation, as evidenced by the significant increase in cell viability and decrease in iNOS, COX2, IL1beta and IL6 expression levels. Furthermore, treatment of cells with NaHS significantly decreased the expression of caspase3, which suggested that NaHS attenuated HGinduced apoptosis. In conclusion, the results of the present study provided evidence to suggest that exogenous H2S protects against HGinduced cytotoxicity and inflammation in H9c2 cardiac cells. H2S may exert these cytoprotective effects via inhibition of the p38MAPK/NFkappaB, COX2 and iNOS signaling pathways

(21) Hu HJ, Jiang ZS, Zhou SH, Liu QM. Hydrogen sulfide suppresses angiotensin II-stimulated endothelin-1 generation and subsequent cytotoxicity-induced endoplasmic reticulum stress in endothelial cells via NF-kappaB. Mol Med Rep 2016 Nov;14(5):4729-40. Abstract: The effects of hydrogen sulfide (H2S) and the nuclear factor kappaB (NF-kappaB) signaling pathway in angiotensin II (AngII)-induced endothelin-1 (ET-1) expression and subsequent cytotoxicity remain unclear. The present study aimed to investigate the hypothesis that H2S protects human umbilical vein endothelial cells (HUVECs) against AngIIstimulated ET1 generation and subsequent cytotoxicityinduced endoplasmic reticulum stress via the NFkappaB signaling pathway. The results of the present study demonstrated that AngII significantly upregulated the expression levels of ET1, glucoseregulated protein 78, CCAATenhancerbinding protein homologous protein, phosphorylated (p)p65 and inducible nitric oxide synthase; stimulated nitric oxide production; suppressed the expression and activity of cystathionine-gamma-lyase (CSE), a H2S synthetase; and decreased cell viability. Conversely, BQ788 (an ET1 receptor antagonist) exhibited an inhibitory effect on the AngIImediated suppression of CSE expression and activity in HUVECs. The effects of AngII were abrogated by sodium hydrosulfide (NaHS, an H2S donor), BQ788 or pyrrolidinedithiocarbamic acid (PDTC, an inhibitor of NFkappaB). Furthermore, pretreatment with NaHS or PDTC attenuated AngIIinduced apoptosis and cleaved caspase-12 generation. The pretreatment of

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HUVECs with BQ788 prior to AngII exposure mimicked the inhibitory effect of NaHS on the expression of pp65 induced by AngII. In conclusion, the present study provides evidence that exogenous H-2S attenuates AngIIinduced inflammation and cytotoxicity via inhibition of the ET1/NFkappaB signaling pathway in HUVECs

(22) Mard SA, Ahmadi I, Ahangarpour A, Gharib-Naseri MK, Badavi M. Delayed gastric emptying in diabetic rats caused by decreased expression of cystathionine gamma lyase and H2 S synthesis: in vitro and in vivo studies. Neurogastroenterol Motil 2016 Nov;28(11):1677-89. Abstract: BACKGROUND: This study aimed to evaluate the role of H2 S on gastric emptying rate (GER) and also to determine the effect of gastric distention on mRNA and protein expression of cystathionine beta-lyase (CBS) and cystathionine gamma-synthase (CSE) in diabetic-gastroparetic and normal rats. METHODS: Adult normal rats intraperitoneally received either propargylglycine (PAG), L-cysteine or NaHS 30 min prior to GER marker (acetaminophen) to investigate H2 S involvement in GER and the same protocols were performed in diabetes-induced gastroparesis rats. The role of calcitonin gene related peptide (CGRP) neurons in the prokinetic effect of endogenous H2 S on GER was determined. The level of CBS and CSE expressions in response to gastric distention were also determined. The effect of H2 S on frequency and tension of spontaneous contractions of gastric smooth muscle strips was investigated. KEY RESULTS: Our results showed that: (i) H2 S and L-cysteine increased GER in gastroparetic and normal rats. (ii) The increased levels of CSE expression in response to gastric distention in diabetic rats were lower than in normal rats. (iii) PAG inhibited the excitatory effect of capsaicin on GER and on tension of spontaneous contractions of strips. (iv) Hydrogen sulphide increased the frequency and tension of spontaneous contractions of gastric strip muscles in normal and diabetic rats. CONCLUSIONS & INFERENCES: The results showed that delayed GER in diabetic rats can be due to down-regulation of H2 S biosynthesis enzyme, CSE and suggested that a potential prokinetic role for H2 S to treat the delayed gastric emptying in diabetic patients

(23) Coavoy-Sanchez SA, Rodrigues L, Teixeira SA, Soares AG, Torregrossa R, Wood ME, et al. Hydrogen sulfide donors alleviate itch secondary to the activation of type-2 protease activated receptors (PAR-2) in mice. Pharmacol Res 2016 Nov;113(Pt A):686-94. Abstract: Hydrogen sulfide (H2S) has been highlighted as an endogenous signaling molecule and we have previously found that it can inhibit histamine-mediated itching. Pruritus is the most common symptom of cutaneous diseases and anti-histamines are the usual treatment; however, anti-histamine-resistant pruritus is common in some clinical settings. In this way, the involvement of mediators other than histamine in the context of pruritus requires new therapeutic targets. Considering that the activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus both in rodents and humans, in this study we investigated the effect of H2S donors on the acute scratching behavior mediated by PAR-2 activation in mice, as well as some of the possible pharmacological mechanisms involved. The intradermal injection of the PAR-2 peptide agonist SLIGRL-NH2 (8-80nmol) caused a dose-dependent scratching that was unaffected by intraperitoneal pre-treatment with the histamine H1 antagonist pyrilamine (30mg/kg). Co-injection of SLIGRL-NH2 (40nmol) with either the slow-release H2S donor GYY4137 (1 and 3nmol) or the spontaneous donor NaHS (1 and 0.3nmol) significantly reduced pruritus. Co-treatment with the KATP channel blocker glibenclamide (200nmol) or the nitric oxide (NO) donor sodium nitroprusside (10nmol) abolished the antipruritic effects of NaHS; however, the specific soluble guanylyl cyclase inhibitor ODQ (30mug) had no significant effects. The transient receptor potential ankyrin type 1 (TRPA1) antagonist HC-030031 (20mug) significantly reduced SLIGRL-NH2-induced pruritus; however pruritus induced by the TRPA1 agonist AITC (1000nmol) was unaffected by NaHS. Based on these data, we conclude that pruritus secondary to PAR-2 activation can be reduced by H2S, which acts through KATP channel opening and involves NO in a cyclic guanosine monophosphate (cGMP)-independent manner. Furthermore, TRPA1 receptors

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mediate the pruritus induced by activation of PAR-2, but H2S does not interfere with this pathway. These results provide additional support for the development of new therapeutical alternatives, mainly intended for treatment of pruritus in patients unresponsive to anti-histamines

(24) Huang CW, Feng W, Peh MT, Peh K, Dymock BW, Moore PK. A novel slow-releasing hydrogen sulfide donor, FW1256, exerts anti-inflammatory effects in mouse macrophages and in vivo. Pharmacol Res 2016 Nov;113(Pt A):533-46. Abstract: Exogenous hydrogen sulfide (H2S) is known to exert anti-inflammatory effects both in macrophages and in animal models. In this study, we first showed that NaHS caused a concentration dependent reduction in TNFalpha and IL-6 secretion in LPS-stimulated RAW264.7 macrophages in the absence of cell death. Thereafter, we screened a series of novel slow H2S donors for similar activity. One such compound, FW1256, concentration dependently decreased TNFalpha, IL-6, PGE2 and NO generation in LPS-stimulated RAW264.7 macrophages and BMDMs. FW1256 also significantly reduced IL-1beta, COX-2 and iNOS mRNA and protein in LPS-stimulated RAW264.7 macrophages. Mechanistically, FW1256 decreased NFkappaB activation as evidenced by reduced cytosolic phospho-IkappaBalpha levels and reduced nuclear p65 levels in LPS-stimulated RAW264.7 macrophages treated with FW1256. Using a H2S fluorescent probe in FW1256-treated RAW264.7 macrophages, H2S release from FW1256 was apparent over a period of 24h in these cells. Moreover, the effect of FW1256 on TNFalpha and IL-6 by FW1256 in LPS-stimulated RAW264.7 macrophages was reversed by treatment with the H2S scavenger, vitamin B12a. FW1256 had no cytotoxic effect on LPS-stimulated RAW264.7 macrophages or BMDMs. In vivo, FW1256 administration also reduced IL-1beta, TNFalpha, nitrate/nitrite and PGE2 levels in LPS-treated mice. We show here a novel slow H2S-releasing compound that exerts anti-inflammatory effects in macrophages and in vivo. FW1256 may be a useful tool to study the biological effects of exogenous H2S and could also have future therapeutic value in inflammatory conditions

(25) Cortese-Krott MM, Pullmann D, Feelisch M. Nitrosopersulfide (SSNO-) targets the Keap-1/Nrf2 redox system. Pharmacol Res 2016 Nov;113(Pt A):490-9. Abstract: Nitric oxide (NO), hydrogen sulfide and polysulfides have been proposed to contribute to redox signaling by activating the Keap-1/Nrf2 stress response system. Nitrosopersulfide (SSNO-) recently emerged as a bioactive product of the chemical interaction of NO or nitrosothiols with sulfide; upon decomposition it generates polysulfides and free NO, triggering the activation of soluble guanylate cyclase, inducing blood vessel relaxation in vitro and lowering blood pressure in vivo. Whether

(26) Monti M, Terzuoli E, Ziche M, Morbidelli L. H2S dependent and independent anti-inflammatory activity of zofenoprilat in cells of the vascular wall. Pharmacol Res 2016 Nov;113(Pt A):426-37. Abstract: Cardiovascular diseases as atherosclerosis are associated to an inflammatory state of the vessel wall which is accompanied by endothelial dysfunction, and adherence and activation of circulating inflammatory cells. Hydrogen sulfide, a novel cardiovascular protective gaseous mediator, has been reported to exert anti-inflammatory activity. We have recently demonstrated that the SH containing ACE inhibitor zofenoprilat, the active metabolite of zofenopril, controls the angiogenic features of vascular endothelium through H2S enzymatic production by cystathionine gamma lyase (CSE). Based on H2S donor/generator property of zofenoprilat, the objective of this study was to evaluate whether zofenoprilat exerts anti-inflammatory activity in vascular cells through its ability to increase H2S availability. Here we found that zofenoprilat, in a CSE/H2S-mediated manner, abolished all the inflammatory features induced by interlukin-1beta (IL-1beta) in human umbilical vein endothelial cells (HUVEC), especially the NF-kappaB/cyclooxygenase-2 (COX-2)/prostanoid biochemical pathway. The pre-incubation with zofenoprilat/CSE dependent H2S prevented IL-1beta induced paracellular

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hyperpermeability through the control of expression and localization of cell-cell junctional markers ZO-1 and VE-cadherin. Moreover, zofenoprilat/CSE dependent H2S reduced the expression of the endothelial markers CD40 and CD31, involved in the recruitment of circulating mononuclear cells and platelets. Interestingly, this anti-inflammatory activity was also confirmed in vascular smooth muscle cells and fibroblasts as zofenoprilat reduced, in both cell lines, proliferation, migration and COX-2 expression induced by IL-1beta, but independently from the SH moiety and H2S availability. These in vitro data document the anti-inflammatory activity of zofenoprilat on vascular cells, reinforcing the cardiovascular protective effect of this multitasking drug

(27) Ahmad A, Szabo C. Both the H2S biosynthesis inhibitor aminooxyacetic acid and the mitochondrially targeted H2S donor AP39 exert protective effects in a mouse model of burn injury. Pharmacol Res 2016 Nov;113(Pt A):348-55. Abstract: Hydrogen sulfide (H2S) exerts beneficial as well as deleterious effects in various models of critical illness. Here we tested the effect of two different pharmacological interventions: (a) inhibition of H2S biosynthesis using the cystathionine-beta-synthase (CBS)/cystathionine-gamma-lyase (CSE) inhibitor aminooxyacetic acid (AOAA) and the mitochondrially targeted H2S donor [10-oxo-10-[4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy]decyl]triphenyl-phosphonium (AP39). A 30% body surface area burn injury was induced in anesthetized mice; animals were treated with vehicle, AOAA (10mg/kg i.p. once or once a day for 6days), or AP39 (0.3mg/kg/day once or once a day for 6days). In two separate groups, animals were sacrificed, at 24h post-burn or on Day 7 post-burn, blood and lungs were collected and the following parameters were evaluated: myeloperoxidase (MPO) and malondialdehyde (MDA) in lung homogenates, plasma cytokines (Luminex analysis) and circulating indicators of organ dysfunction (Vetscan analysis). Lung MPO levels (an index of neutrophil infiltration) and MDA levels (an index of oxidative stress) were significantly increased in response to burn injury both at 24h and at 7days; both AOAA and AP39 attenuated these increases. From a panel of inflammatory cytokines (TNFalpha, IL-1beta, IL-6, IL-10, MCP-1, MIP-2, VEGF and IFNgamma) in the plasma, IL-6 and IL-10 levels were markedly elevated at 24h and VEGF was slightly elevated. IL-6 remained highly elevated at 7days post-burn while IL-10 levels decreased, but remained slightly elevated over baseline 7days post-burn. The changes in cytokine levels were attenuated both by AP39 and AOAA at both time points studied. The burn-induced increases in the organ injury markers ALP and ALT, amylase and creatinine were reduced by both AOAA and AP39. We conclude that both H2S biosynthesis inhibition (using AOAA) and H2S donation (using AP39) suppresses inflammatory mediator production and reduces multi-organ injury in a murine model of burn injury, both at an early time point (when systemic H2S levels are elevated) and at a later time point (at which time systemic H2S levels have returned to baseline). These findings point to the complex pathogenetic role of H2S in burns

(28) Testai L, Marino A, Piano I, Brancaleone V, Tomita K, Di Cesare ML, et al. The novel H2S-donor 4-carboxyphenyl isothiocyanate promotes cardioprotective effects against ischemia/reperfusion injury through activation of mitoKATP channels and reduction of oxidative stress. Pharmacol Res 2016 Nov;113(Pt A):290-9. Abstract: The endogenous gasotransmitter hydrogen sulphide (H2S) is an important regulator of the cardiovascular system, particularly of myocardial function. Moreover, H2S exhibits cardioprotective activity against ischemia/reperfusion (I/R) or hypoxic injury, and is considered an important mediator of "ischemic preconditioning", through activation of mitochondrial potassium channels, reduction of oxidative stress, activation of the endogenous "anti-oxidant machinery" and limitation of inflammatory responses. Accordingly, H2S-donors, i.e. pro-drugs able to generate exogenous H2S, are viewed as promising therapeutic agents for a number of cardiovascular diseases. The novel H2S-donor 4-carboxy phenyl-isothiocyanate (4CPI), whose vasorelaxing effects were recently reported, was tested here in different experimental models of myocardial I/R. In Langendorff-perfused rat hearts subjected to I/R, 4CPI significantly improved the post-

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ischemic recovery of myocardial functional parameters and limited tissue injury. These effects were antagonized by 5-hydroxydecanoic acid (a blocker of mitoKATP channels). Moreover, 4CPI inhibited the formation of reactive oxygen species. We found the whole battery of H2S-producing enzymes to be present in myocardial tissue: cystathionine gamma-lyase (CSE), cystathionine beta-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (MPST). Notably, 4CPI down-regulated the post-ischemic expression of CSE. In Langendorff-perfused mouse hearts, 4CPI reduced the post-ischemic release of norepinephrine and the incidence of ventricular arrhythmias. In both rat and mouse hearts, 4CPI did not affect the degranulation of resident mast cells. In isolated rat cardiac mitochondria, 4CPI partially depolarized the mitochondrial membrane potential; this effect was antagonized by ATP (i.e., the physiological inhibitor of KATP channels). Moreover, 4CPI abrogated calcium uptake in the mitochondrial matrix. Finally, in an in vivo model of acute myocardial infarction in rats, 4CPI significantly decreased I/R-induced tissue injury. In conclusion, H2S-donors, and in particular isothiocyanate-based H2S-releasing drugs like 4CPI, can actually be considered a suitable pharmacological option in anti-ischemic therapy

(29) Weber GJ, Pushpakumar S, Tyagi SC, Sen U. Homocysteine and hydrogen sulfide in epigenetic, metabolic and microbiota related renovascular hypertension. Pharmacol Res 2016 Nov;113(Pt A):300-12. Abstract: Over the past several years, hydrogen sulfide (H2S) has been shown to be an important player in a variety of physiological functions, including neuromodulation, vasodilation, oxidant regulation, inflammation, and angiogenesis. H2S is synthesized primarily through metabolic processes from the amino acid cysteine and homocysteine in various organ systems including neuronal, cardiovascular, gastrointestinal, and kidney. Derangement of cysteine and homocysteine metabolism and clearance, particularly in the renal vasculature, leads to H2S biosynthesis deregulation causing or contributing to existing high blood pressure. While a variety of environmental influences, such as diet can have an effect on H2S regulation and function, genetic factors, and more recently epigenetics, also have a vital role in H2S regulation and function, and therefore disease initiation and progression. In addition, new research into the role of gut microbiota in the development of hypertension has highlighted the need to further explore these microorganisms and how they influence the levels of H2S throughout the body and possibly exploiting microbiota for use of hypertension treatment. In this review, we summarize recent advances in the field of hypertension research emphasizing renal contribution and how H2S physiology can be exploited as a possible therapeutic strategy to ameliorate kidney dysfunction as well as to control blood pressure

(30) Katsouda A, Bibli SI, Pyriochou A, Szabo C, Papapetropoulos A. Regulation and role of endogenously produced hydrogen sulfide in angiogenesis. Pharmacol Res 2016 Nov;113(Pt A):175-85. Abstract: Recent studies have implicated endogenously produced H2S in the angiogenic process. On one hand, pharmacological inhibition and silencing of the enzymes involved in H2S synthesis attenuate the angiogenic properties of endothelial cells, including proliferation, migration and tube-like structure network formation. On the other hand, enhanced production of H2S by substrate supplementation or over-expression of H2S-producing enzymes leads to enhanced angiogenic responses in cultured endothelial cells. Importantly, H2S up-regulates expression of the key angiogenic factor vascular endothelial growth factor (VEGF) and contributes to the angiogenic signaling in response to VEGF. The signaling pathways mediating H2S-induced angiogenesis include mitogen-activated protein kinases, phosphoinositide-3 kinase, nitric oxide/cGMP-regulated cascades and ATP-sensitive potassium channels. Endogenously produced H2S has also been shown to facilitate neovascularization in prototypical model systems in vivo, and to contribute to wound healing, post-ischemic angiogenesis in the heart and other tissues, as well as in tumor angiogenesis. Targeting of H2S synthesizing enzymes might offer novel therapeutic opportunities for angiogenesis-related diseases

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(31) Gero D, Torregrossa R, Perry A, Waters A, Le-Trionnaire S, Whatmore JL, et al. The novel mitochondria-targeted hydrogen sulfide (H2S) donors AP123 and AP39 protect against hyperglycemic injury in microvascular endothelial cells in vitro. Pharmacol Res 2016 Nov;113(Pt A):186-98. Abstract: The development of diabetic vascular complications is initiated, at least in part, by mitochondrial reactive oxygen species (ROS) production in endothelial cells. Hyperglycemia induces superoxide production in the mitochondria and initiates changes in the mitochondrial membrane potential that leads to mitochondrial dysfunction. Hydrogen sulfide (H2S) supplementation has been shown to reduce the mitochondrial oxidant production and shows efficacy against diabetic vascular damage in vivo. However, the half-life of H2S is very short and it is not specific for the mitochondria. We have therefore evaluated two novel mitochondria-targeted anethole dithiolethione and hydroxythiobenzamide H2S donors (AP39 and AP123 respectively) at preventing hyperglycemia-induced oxidative stress and metabolic changes in microvascular endothelial cells in vitro. Hyperglycemia (HG) induced significant increase in the activity of the citric acid cycle and led to elevated mitochondrial membrane potential. Mitochondrial oxidant production was increased and the mitochondrial electron transport decreased in hyperglycemic cells. AP39 and AP123 (30-300nM) decreased HG-induced hyperpolarisation of the mitochondrial membrane and inhibited the mitochondrial oxidant production. Both H2S donors (30-300nM) increased the electron transport at respiratory complex III and improved the cellular metabolism. Targeting H2S to mitochondria retained the cytoprotective effect of H2S against glucose-induced damage in endothelial cells suggesting that the molecular target of H2S action is within the mitochondria. Mitochondrial targeting of H2S also induced >1000-fold increase in the potency of H2S against hyperglycemia-induced injury. The high potency and long-lasting effect elicited by these H2S donors strongly suggests that these compounds could be useful against diabetic vascular complications

(32) Modis K, Ju Y, Ahmad A, Untereiner AA, Altaany Z, Wu L, et al. S-Sulfhydration of ATP synthase by hydrogen sulfide stimulates mitochondrial bioenergetics. Pharmacol Res 2016 Nov;113(Pt A):116-24. Abstract: Mammalian cells can utilize hydrogen sulfide (H2S) to support mitochondrial respiration. The aim of our study was to explore the potential role of S-sulfhydration (a H2S-induced posttranslational modification, also known as S-persulfidation) of the mitochondrial inner membrane protein ATP synthase (F1F0 ATP synthase/Complex V) in the regulation of mitochondrial bioenergetics. Using a biotin switch assay, we have detected S-sulfhydration of the alpha subunit (ATP5A1) of ATP synthase in response to exposure to H2S in vitro. The H2S generator compound NaHS induced S-sulfhydration of ATP5A1 in HepG2 and HEK293 cell lysates in a concentration-dependent manner (50-300muM). The activity of immunocaptured mitochondrial ATP synthase enzyme isolated from HepG2 and HEK293 cells was stimulated by NaHS at low concentrations (10-100nM). Site-directed mutagenesis of ATP5A1 in HEK293 cells demonstrated that cysteine residues at positions 244 and 294 are subject to S-sulfhydration. The double mutant ATP synthase protein (C244S/C294S) showed a significantly reduced enzyme activity compared to control and the single-cysteine-mutated recombinant proteins (C244S or C294S). To determine whether endogenous H2S plays a role in the basal S-sulfhydration of ATP synthase in vivo, we compared liver tissues harvested from wild-type mice and mice deficient in cystathionine-gamma-lyase (CSE, one of the three principal mammalian H2S-producing enzymes). Significantly reduced S-sulfhydration of ATP5A1 was observed in liver homogenates of CSE-/- mice, compared to wild-type mice, suggesting a physiological role for CSE-derived endogenous H2S production in the S-sulfhydration of ATP synthase. Various forms of critical illness (including burn injury) upregulate H2S-producing enzymes and stimulate H2S biosynthesis. In liver tissues collected from mice subjected to burn injury, we detected an increased S-sulfhydration of ATP5A1 at the early time points post-burn. At later time points (when systemic H2S levels decrease) S-sulfhydration of ATP5A1 decreased as well. In conclusion, H2S

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induces S-sulfhydration of ATP5A1 at C244 and C294. This post-translational modification may be a physiological mechanism to maintain ATP synthase in a physiologically activated state, thereby supporting mitochondrial bioenergetics. The sulfhydration of ATP synthase may be a dynamic process, which may be regulated by endogenous H2S levels under various pathophysiological conditions

(33) Sulen A, Gullaksen SE, Bader L, McClymont DW, Skavland J, Gavasso S, et al. Signaling effects of sodium hydrosulfide in healthy donor peripheral blood mononuclear cells. Pharmacol Res 2016 Nov;113(Pt A):216-27. Abstract: Hydrogen sulfide (H2S) is an endogenous gasotransmitter in human physiology and inflammatory disease, however, with limited knowledge of how signal transduction pathways are involved in immune cells. To examine the effects of sulfide on relevant intracellular signaling in human peripheral blood mononuclear cells (PBMCs), we stimulated healthy donor PBMCs with sodium hydrosulfide (NaHS, 1-1000muM) to mimic H2S stimulation, and analyzed phosphorylation of p38 mitogen activated protein kinase (MAPK) (pT180/pY182), NF-kappaB p65 (pS529), Akt (pS473) and CREB/ATF1 (pS133/pS63) with flow and mass cytometry. In contrast to transient effects in subsets of lymphocytes, classical monocytes demonstrated sustained phosphorylation of p38, Akt and CREB/ATF1. NaHS induced calcium dependent phosphorylation of p38, Akt and CREB, but not NF-kappaB, and the phosphorylation of Akt was partly dependent on p38, indicative of p38-Akt crosstalk. Attenuation of these effects by molecules targeting p38 and Hsp90 indicated Hsp90 as a possible target for H2S-induced activation of p38. These results provide a description of a NaHS-induced signal transduction pathway in human primary immune cells that may have relevance for the role of sulfides in inflammation

(34) Yetik-Anacak G, Dikmen A, Coletta C, Mitidieri E, Dereli M, Donnarumma E, et al. Hydrogen sulfide compensates nitric oxide deficiency in murine corpus cavernosum. Pharmacol Res 2016 Nov;113(Pt A):38-43. Abstract: Erectile dysfunction (ED) is considered as a marker for cardiovascular diseases. Nitric oxide (NO) deficiency is the major cause of erectile dysfunction (ED). The role of hydrogen sulfide (H2S) in erection has recently been recognized and is receiving attention as a pharmacological target. Several studies have focused on the effect of H2S on NO-dependent relaxation, but the role of NO on H2S in penile tissue has not been studied yet. Unlike NO, H2S is mainly synthesized from smooth muscle cells rather than endothelial cells. We hypothesized that H2S may compensate for the decreased NO bioavailability and may be beneficial in severe ED where endothelial dysfunction is present. Thus we studied the effect of NO deficiency on H2S formation and vasorelaxation induced by l-cysteine, which is the substrate of the H2S producing enzymes in mice corpus cavernosum (MCC). NO deficiency induced by Nomega-Nitro-l-arginine (L-NNA) was confirmed by the inhibition of acetylcholine-induced relaxation. l-cysteine, the substrate for the endogenous H2S production, caused a concentration-dependent relaxation that was reduced by CBS/CSE inhibitor aminooxyacetic acid (AOAA) in MCC strips. L-NNA caused a significant increase in l-cysteine-induced relaxation, and this effect was reversed by AOAA. On the contrary, no change in relaxation to NaHS (exogenous H2S donor) in MCC was observed. L-NNA increased H2S formation stimulated by l-cysteine in wild type MCC but not in CSE-/- mice. In parallel, the expression of both cysthationine gamma lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (3-MST) was increased, whereas cysthationine-beta synthase (CBS) was decreased in eNOS-/- MCC. We conclude that H2S plays a compensatory role in the absence of NO by enhancing the relaxation induced by endogenous H2S through CSE and 3-MPST in MCC, without altering downstream mechanisms. We suggest that H2S-targeting drugs may provide the maintenance of compensatory treatment in ED patients. This may be more relevant in ED with severe endothelial dysfunction, as H2S is mainly derived from smooth muscle

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(35) Druzhyna N, Szczesny B, Olah G, Modis K, Asimakopoulou A, Pavlidou A, et al. Screening of a composite library of clinically used drugs and well-characterized pharmacological compounds for cystathionine beta-synthase inhibition identifies benserazide as a drug potentially suitable for repurposing for the experimental therapy of colon cancer. Pharmacol Res 2016 Nov;113(Pt A):18-37. Abstract: Cystathionine-beta-synthase (CBS) has been recently identified as a drug target for several forms of cancer. Currently no potent and selective CBS inhibitors are available. Using a composite collection of 8871 clinically used drugs and well-annotated pharmacological compounds (including the LOPAC library, the FDA Approved Drug Library, the NIH Clinical Collection, the New Prestwick Chemical Library, the US Drug Collection, the International Drug Collection, the 'Killer Plates' collection and a small custom collection of PLP-dependent enzyme inhibitors), we conducted an in vitro screen in order to identify inhibitors for CBS using a primary 7-azido-4-methylcoumarin (AzMc) screen to detect CBS-derived hydrogen sulfide (H2S) production. Initial hits were subjected to counterscreens using the methylene blue assay (a secondary assay to measure H2S production) and were assessed for their ability to quench the H2S signal produced by the H2S donor compound GYY4137. Four compounds, hexachlorophene, tannic acid, aurintricarboxylic acid and benserazide showed concentration-dependent CBS inhibitory actions without scavenging H2S released from GYY4137, identifying them as direct CBS inhibitors. Hexachlorophene (IC50: approximately 60muM), tannic acid (IC50: approximately 40muM) and benserazide (IC50: approximately 30muM) were less potent CBS inhibitors than the two reference compounds AOAA (IC50: approximately 3muM) and NSC67078 (IC50: approximately 1muM), while aurintricarboxylic acid (IC50: approximately 3muM) was equipotent with AOAA. The second reference compound NSC67078 not only inhibited the CBS-induced AzMC fluorescence signal (IC50: approximately 1muM), but also inhibited with the GYY4137-induced AzMC fluorescence signal with (IC50 of approximately 6muM) indicative of scavenging/non-specific effects. Hexachlorophene (IC50: approximately 6muM), tannic acid (IC50: approximately 20muM), benserazide (IC50: approximately 20muM), and NSC67078 (IC50: approximately 0.3muM) inhibited HCT116 colon cancer cells proliferation with greater potency than AOAA (IC50: approximately 300muM). In contrast, although a CBS inhibitor in the cell-free assay, aurintricarboxylic acid failed to inhibit HCT116 proliferation at lower concentrations, and stimulated cell proliferation at 300muM. Copper-containing compounds present in the libraries, were also found to be potent inhibitors of recombinant CBS; however this activity was due to the CBS inhibitory effect of copper ions themselves. However, copper ions, up to 300muM, did not inhibit HCT116 cell proliferation. Benserazide was only a weak inhibitor of the activity of the other H2S-generating enzymes CSE and 3-MST activity (16% and 35% inhibition at 100muM, respectively) in vitro. Benserazide suppressed HCT116 mitochondrial function and inhibited proliferation of the high CBS-expressing colon cancer cell line HT29, but not the low CBS-expressing line, LoVo. The major benserazide metabolite 2,3,4-trihydroxybenzylhydrazine also inhibited CBS activity and suppressed HCT116 cell proliferation in vitro. In an in vivo study of nude mice bearing human colon cancer cell xenografts, benserazide (50mg/kg/days.q.) prevented tumor growth. In silico docking simulations showed that benserazide binds in the active site of the enzyme and reacts with the PLP cofactor by forming reversible but kinetically stable Schiff base-like adducts with the formyl moiety of pyridoxal. We conclude that benserazide inhibits CBS activity and suppresses colon cancer cell proliferation and bioenergetics in vitro, and tumor growth in vivo. Further pharmacokinetic, pharmacodynamic and preclinical animal studies are necessary to evaluate the potential of repurposing benserazide for the treatment of colorectal cancers

(36) Jin Z, Pei Y. Hydrogen sulfide: the shutter button of stomata in plants. Sci China Life Sci 2016 Nov;59(11):1187-8.

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(37) Szabo C. Hydrogen sulfide, an enhancer of vascular nitric oxide signalling: mechanisms and implications. Am J Physiol Cell Physiol 2016 Oct 26;ajpcell. Abstract: Nitric oxide (NO) vascular signalling has long been considered an independent, self-sufficient pathway. However, recent data indicate that the novel gaseous mediator, hydrogen sulfide (H2S), serves as an essential enhancer/stimulator of vascular NO signalling. The current article overviews the multiple levels at which this enhancement/stimulation takes place. The first level of interaction relates to the formation of biologically active hybrid S/N species and the stimulation of NO release from its various stable "pools" (e.g. nitrite). The next interactions occur on the level of endothelial calcium mobilization and PI3K/Akt signaling, increasing the specific activity of endothelial NO synthase (eNOS). The next level of interaction occurs on eNOS itself; H2S directly interacts with the enzyme: the sulfhydration of critical cysteines stabilizes it in its physiological, dimeric state, thereby optimizing eNOS-derived NO production and minimizing superoxide formation. Yet another level of interaction, further downstream, occurs at the level of soluble guanylate cyclase (sGC). H2S contributes to keeping sGC in its NO-responsive, physiological, reduced form. H2S inhibits the vascular cGMP phosphodiesterase (PDE5), which prolongs the biological half-life of cGMP. Finally, H2S-derived polysulfides directly activate cGMP-dependent protein kinase (PKG). Taken together, H2S emerges an essential endogenous enhancer of vascular NO signaling, contributing to vasorelaxation and angiogenesis. When vascular H2S production becomes impaired, the eNOS pathway only operates at a partial capacity. The functional importance of the H2S/NO cooperative interactions is highlighted by the fact that H2S loses many of its cardiovascular beneficial effects when eNOS is inactive

(38) Jin X, Wu S, She M, Jia Y, Hao L, Yin B, et al. A novel fluorescein-based fluorescent probe for detecting H2S and its real applications in blood plasma and biological imaging. Anal Chem 2016 Oct 26. Abstract: A broad-spectrum fluorescent probe, which can be applied to monitoring H2S in various biological systems, has been synthesized. This specific probe was applied to localize the endogenous H2S in living Raw264.7 macrophages cells, HepG2 cells and H9C2 cells. The probe have successfully visualized CBS- and CSE-induced endogenous H2S production and monitored CBS and CSE activity in H9C2 cells. This probe could serve as a powerful molecular imaging tool to further explore the physiological function and the molecular mechanisms of endogenous H2S in living animal systems

(39) Zhang S, Zhu L, Liu H, Yang G. Structure and Electronic Properties of Fe2SH3 Compound under High Pressure. Inorg Chem 2016 Oct 26. Abstract: Inspired by the diverse properties of hydrogen sulfide, iron sulfide, and iron hydrides, we combine first-principles calculations with structure prediction to find stable structures of Fe-S-H ternary compounds with various FexSyHz (x = 1-2; y = 1-2; z = 1-6) compositions under high pressure with the aim of finding novel functional materials. It is found that Fe2SH3 composition stabilizes into an orthorhombic structure with Cmc21 symmetry, whose remarkable feature is that it contains dumbbell-type Fe with an Fe-Fe distance of 2.435 A at 100 GPa, and S and H atoms directly bond with the Fe atoms exhibiting ionic bonding. The high density of states at the Fermi level, mainly coming from the contribution of Fe-3d, indicates that it satisfies the Stoner ferromagnetic condition. Notably, its ferromagnetic ordering gradually decreases with increasing pressure, and eventually collapses at a pressure of 173 GPa. As a consequence, magnetic and nonmagnetic transition can be achieved by controlling the pressure. In addition, there is a very weak electron-phonon coupling in Cmc21-structured Fe2SH3. The different superconducting mechanisms between Fe2SH3 and H3S were compared and analyzed

(40) Lu D, Qi J, Yang M, Behler J, Song H, Li J. Mode specific dynamics in the H2 + SH --> H + H2S reaction. Phys Chem Chem Phys 2016 Oct 26;18(42):29113-21. Abstract: Full-dimensional coupled-channel quantum scattering and quasi-classical trajectory calculations have been carried out and analyzed to unravel the mode specific

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dynamics in the H2 + SH --> H + H2S reaction employing two different accurate neural network representations of an ab initio global potential energy surface at the coupled cluster level. Strong mode selectivity was found and partially rationalized by the sudden vector projection model. Specifically, the vibrational excitation of H2 remarkably enhances the reactivity while its rotational excitation only slightly promotes the reaction. On the other hand, the reactant SH acts as a good spectator, whose vibrational and rotational excitations have a negligible effect on the reaction

(41) Wang W, Wu Y. Combination of zero-valent iron and anaerobic microorganisms immobilized in luffa sponge for degrading 1,1,1-trichloroethane and the relevant microbial community analysis. Appl Microbiol Biotechnol 2016 Oct 25. Abstract: 1,1,1-Trichloroethane (1,1,1-TCA), a dense non-aqueous phase liquid (DNAPL), is relatively slow to remediate naturally; combination of zero-valent iron and immobilized microorganism is a potential means to accelerate DNAPL biodegradation. We first adopted high density luffa sponge (HDLS) as immobilized microorganism carrier. The experimental results demonstrated that (1) the supernatant liquid microorganisms were the optimal immobilized microorganisms for HDLS and (2) the combination of zero-valent iron and immobilized microorganisms accelerated 1,1,1-TCA transformation. Furthermore, in the long-term remediation process, anaerobic microorganisms produced reductant H2S which was beneficial to zero-valent iron PRBs. Through further study of the microbial community, we found that majority of the sulfate-reducing bacteria (SRB) perfectly adapted to the process of 1,1,1-TCA co-metabolism dechlorination. Desulfobulbus and Desulfococcus potentially were the special SRB that contributed significantly to TCA co-metabolism. Additionally, 1,1,1-TCA induced the generation of new SRB and stimulated the growth of majority of dominating methanogens. The results indicated that they played a constructive role in accelerating the dechlorination of 1,1,1-TCA, reduction of sulfate, and improving the production of CH4. Consequently, combination of zero-valent iron and immobilized microorganisms for remediating groundwater by contaminated 1,1,1-TCA is a sustainable and green remediation technology. Especially for groundwater of

(42) Zeng Z, Altarawneh M, Oluwoye I, Glarborg P, Dlugogorski BZ. Inhibition and Promotion of Pyrolysis by Hydrogen Sulfide (H2S) and Sulfanyl Radical (SH). J Phys Chem A 2016 Oct 25. Abstract: This study resolves the interaction of sulfanyl radical (SH) with aliphatic (C1-C4) hydrocarbons, using CBS-QB3 based calculations. We obtained the C-H dissociation enthalpies and located the weakest link in each hydrocarbon. Subsequent computations revealed that, H abstraction by SH from the weakest CH sites in alkenes and alkynes, except for ethylene, appears noticeably exothermic. Furthermore, abstraction of H from propene, 1-butene and iso-butene displays pronounced spontaneity (i.e., DeltarG degrees < -20 kJ mol-1 between

(43) Gao L, Wu TW, Ni X. Gas transmitters in female reproductive system. Sheng Li Xue Bao 2016 Oct 25;68(5):611-20. Abstract: Nitric oxide, carbon monoxide and hydrogen sulfide synthesized endogenously in living organisms produce an array of disparate biological effects, so as to be considered as gas transmitters. These three gaseous molecules play important roles in many physiological and pathological processes in the bodies, such as the regulation of vascular tone and inflammatory responses as well as reproductive function. This review mainly focuses on the distribution and biological functions of these three gas transmitters in female reproductive tissues

(44) Zheng H, Zhu HY, Zhang XY, Wang M, Xiao Y, Xu GY, et al. Upregulation of cystathionine beta-synthetase in the arcuate nucleus produces pain hypersensitivity via PKC upregulation and GluN2B phosphorylation in rats with chronic pancreatitis. Sheng Li Xue Bao 2016 Oct 25;68(5):575-84.

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Abstract: Hydrogen sulfide (H2S) contributes to visceral hyperalgesia in primary sensory neurons, but its role in central nervous system remains largely unknown. This study was to investigate the roles and underlying mechanisms of H2S and its endogenous synthesis enzymes in the arcuate nucleus (ARC) in rat pancreatic hyperalgesia. Chronic pancreatitis (CP) was induced in male adult Sprague-Dawley rats by intra-pancreatic ductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Western blot analysis was performed to detect protein expression in the ARC. CP markedly upregulated cystathionine beta-synthetase (CBS) expression but did not alter cystathionine-gamma-lyase level in the ARC at 4 weeks after TNBS injection. Although the expression of total GluN2B was not altered, CP greatly enhanced the phosphorylation level of GluN2B in the ARC when compared with age- and sex-matched control rats. CP also significantly increased expression of protein kinase Cgamma (PKCgamma) in the ARC. Arcuate microinjection of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA, an inhibitor of CBS) significantly attenuated abdominal pain in CP rats in a dose-dependent manner and reversed the CP-induced upregulation of p-GluN2B and PKCgamma in the ARC. Furthermore, the GluN2B inhibitor or specific PKC inhibitor chelerythrine significantly attenuated abdominal hyperalgesia in CP rats. The p-GluN2B expression was also suppressed by PKC inhibitor. Taken together, our results suggest that the upregulation of CBS in the ARC leads to an activation of GluN2B via PKCgamma, which may play an important role in generation of pain hypersensitivity of CP

(45) Zhao Y, Pluth MD. Hydrogen Sulfide Donors Activated by Reactive Oxygen Species. Angew Chem Int Ed Engl 2016 Oct 24. Abstract: Hydrogen sulfide (H2 S) exhibits promising protective effects in many (patho)physiological processes, as evidenced by recent reports using synthetic H2 S donors in different biological models. Herein, we report the design and evaluation of compounds denoted PeroxyTCM, which are the first class of reactive oxygen species (ROS)-triggered H2 S donors. These donors are engineered to release carbonyl sulfide (COS) upon activation, which is quickly hydrolyzed to H2 S by the ubiquitous enzyme carbonic anhydrase (CA). The donors are stable in aqueous solution and do not release H2 S until triggered by ROS, such as hydrogen peroxide (H2 O2 ), superoxide (O2- ), and peroxynitrite (

(46) Cebova M, Kosutova M, Pechanova O. Cardiovascular effects of gasotransmitter donors. Physiol Res 2016 Oct 24;65(Supplementum 3):S291-S307. Abstract: Gasotransmitters represent a subfamily of the endogenous gaseous signaling molecules that include nitric oxide (NO), carbon monoxide (CO), and hydrogen sulphide (H(2)S). These particular gases share many common features in their production and function, but they fulfill their physiological tasks in unique ways that differ from those of classical signaling molecules found in tissues and organs. These gasotransmitters may antagonize or potentiate each other's cellular effects at the level of their production, their downstream molecular targets and their direct interactions. All three gasotransmitters induce vasodilatation, inhibit apoptosis directly or by increasing the expression of anti-apoptotic genes, and activate antioxidants while inhibiting inflammatory actions. NO and CO may concomitantly participate in vasorelaxation, anti-inflammation and angiogenesis. NO and H(2)S collaborate in the regulation of vascular tone. Finally, H(2)S may upregulate the heme oxygenase/carbon monoxide (HO/CO) pathway during hypoxic conditions. All three gasotransmitters are produced by specific enzymes in different cell types that include cardiomyocytes, endothelial cells and smooth muscle cells. As translational research on gasotransmitters has exploded over the past years, drugs that alter the production/levels of the gasotransmitters themselves or modulate their signaling pathways are now being developed. This review is focused on the cardiovascular effects of NO, CO, and H(2)S. Moreover, their donors as drug targeting the cardiovascular system are briefly described

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(47) Cacanyiova S, Berenyiova A, Kristek F. The role of hydrogen sulphide in blood pressure regulation. Physiol Res 2016 Oct 24;65(Supplementum 3):S273-S289. Abstract: Cardiovascular studies have confirmed that hydrogen sulphide (H(2)S) is involved in various signaling pathways in both physiological and pathological conditions, including hypertension. In contrast to nitric oxide (NO), which has a clear vasorelaxant action, H(2)S has both vasorelaxing and vasoconstricting effects on the cardiovascular system. H(2)S is an important antihypertensive agent, and the reduced production of H(2)S and the alterations in its functions are involved in the initiation of spontaneous hypertension. Moreover, cross-talk between H(2)S and NO has been reported. NO-H(2)S interactions include reactions between the molecules themselves, and each has been shown to regulate the endogenous production of the other. In addition, NO and H(2)S can interact to form a nitrosothiol/s complex, which has original properties and represents a novel nitroso-sulphide signaling pathway. Furthermore, recent results have shown that the interaction between H(2)S and NO could be involved in the endothelium-regulated compensatory mechanisms that are observed in juvenile spontaneously hypertensive rats. The present review is devoted to role of H(2)S in vascular tone regulation. We primarily focus on the mechanisms of H(2)S-NO interactions and on the role of H(2)S in blood pressure regulation in normotensive and spontaneously hypertensive rats

(48) Yuan L, Pan Y, Ren TB, Cheng D, Zeng ZB, Zhang XB. A Selective Near-Infrared Fluorescent Probe for in Vivo Imaging of Thiophenols From a Focused Library. Chem Asian J 2016 Oct 21. Abstract: Thiophenols are highly toxic industrial materials that once released, will accumulate in environment and ultimately into human bodies, causing serious health problems. To achieve their selective and sensitive detection, herein a novel near-infrared fluorescent probe CCP-1 from a focused library was developed for thiophenol species. Our studies show that CCP-1 displays a thiophenol-triggered 28-fold fluorescence intensity enhancement at 706 nm, with a detection limit of 34 nM observed. It is also able to differentiate thiophenols from various other thiol-containing analytes including hydrogen sulfide, hydrogen persulfide and aliphatic thiols. In total, the desirable properties (e.g. excitation/emission in NIR region, good cell-membrane permeability, intracellular stability, and low cytotoxicity) make CCP-1 a highly potential candidate for thiophenol detection both in vitro and in vivo. In addition, CCP-1, for the first time, was successfully visualized thiophenols in mice models of thiophenol inhalation

(49) Xia N, Li H. The role of perivascular adipose tissue in obesity-induced vascular dysfunction. Br J Pharmacol 2016 Oct 20. Abstract: Under physiological conditions, perivascular adipose tissue (PVAT) attenuates agonist-induced vasoconstriction by releasing vasoactive molecules including hydrogen peroxide, angiotensin 1-7, adiponectin, methyl palmitate, hydrogen sulfide, nitric oxide (NO) and leptin. This anticontractile function of PVAT is lost under conditions of obesity. The central mechanism underlying PVAT dysfunction in obesity is likely to be an "obesity triad" (consisting of PVAT hypoxia, inflammation and oxidative stress) that leads to dysregulation of PVAT-derived vasoregulators. The PVAT production of hydrogen sulfide, NO and adiponectin is reduced in obesity, whereas the vasodilator response to leptin is impaired (vascular leptin resistance). Strikingly, the vasodilator response to acetylcholine is reduced only in PVAT-containing, but not in PVAT-free thoracic aorta isolated from diet-induced obese mice, indicating a unique role of PVAT in obesity-induced vascular dysfunction. Furthermore, PVAT dysfunction has also been observed in small arteries isolated from gluteal/visceral fat biopsy samples of obese individuals. Therefore, PVAT may represent a new therapeutic target for vascular complications in obesity. A number of approaches are being currently tested under experimental conditions. Potential therapeutic strategies improving PVAT function include body weight reduction, enhancing PVAT hydrogen sulfide release (e.g. rosiglitazone, atorvastatin and cannabinoid CB1 receptor agonists) and NO production (e.g. arginase inhibitors), inhibition of the renin-angiotensin-aldosterone system, inhibition of inflammation with melatonin or cytokine

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antagonists, activators of AMP-activated kinase (e.g. metformin, resveratrol and diosgenin) and adiponectin releasers or expression enhancers

(50) Ziogas V, Tanou G, Belghazi M, Diamantidis G, Molassiotis A. Characterization of beta-amino- and gamma-amino butyric acid-induced citrus seeds germination under salinity using nanoLC-MS/MS analysis. Plant Cell Rep 2016 Oct 19. Abstract: KEY MESSAGE: BABA or GABA induces salinity acclimation during citrus seeds germination via alternation of specific proteins (e.g., citrin). The impact of four elicitors, namely hydrogen peroxide (H2O2), beta-amino butyric acid (BABA), gamma-amino butyric acid (GABA) and hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS), in citrus seed germination under salinity (150 mM NaCl) was tested. The germination potential was adversely affected by NaCl-alone treatment. Pretreatment with H2O2 or the NaHS-H2S donor prior to salinity had no significant effect in germination process, however, BABA and GABA substantially improved seed acclimation to salinity, as evidenced by increased germination percentage and radicle length. Total soluble proteins of radicle and cotyledons were separated by 1DE SDS-PAGE and proteins zones were analyzed by mass spectrometry. In total, 27 and 3 proteins were identified in radicle and cotyledons, respectively. The identified proteins mainly include redox-regulated enzymes (i.e., glutathione S-transferase, dehydroascorbate reductase, Mn-superoxide dismutase, glutathione peroxidase), energy-related proteins (i.e., isocitrate lyase, malate synthase, pyruvate decarboxylase), stress proteins (i.e., stress-related protein, miraculin, thaumatin, disulfide isomerase), storage proteins (i.e., vicilin, Pis v 1 allergen 2S albumin) and transcriptional regulators (i.e., MarR family transcriptional regulator, MADS544 protein). Pretreatments with BABA or GABA altered the accumulation of protein zones exclusively corresponding to citrin, indicating that this protein may serve as a marker for salinity acclimation in citrus seeds

(51) Zhu H, Fan J, Du J, Peng X. Fluorescent Probes for Sensing and Imaging within Specific Cellular Organelles. Acc Chem Res 2016 Oct 18;49(10):2115-26. Abstract: Fluorescent probes have become powerful tools in biosensing and bioimaging because of their high sensitivity, specificity, fast response, and technical simplicity. In the last decades, researchers have made remarkable progress in developing fluorescent probes that respond to changes in microenvironments (e.g., pH, viscosity, and polarity) or quantities of biomolecules of interest (e.g., ions, reactive oxygen species, and enzymes). All of these analytes are specialized to carry out vital functions and are linked to serious disorders in distinct subcellular organelles. Each of these organelles plays a specific and indispensable role in cellular processes. For example, the nucleus regulates gene expression, mitochondria are responsible for aerobic metabolism, and lysosomes digest macromolecules for cell recycling. A certain organelle requires specific biological species and the appropriate microenvironment to perform its cellular functions, while breakdown of the homeostasis of biomolecules or microenvironmental mutations leads to organelle malfunctions, which further cause disorders or diseases. Fluorescent probes that can be targeted to both specific organelles and biochemicals/microenvironmental factors are capable of reporting localized bioinformation and are potentially useful for gaining insight into the contributions of analytes to both healthy and diseased states. In this Account, we review our recent work on the development of fluorescent probes for sensing and imaging within specific organelles. We present an overview of the design, photophysical properties, and biological applications of the probes, which can localize to mitochondria, lysosomes, the nucleus, the Golgi apparatus, and the endoplasmic reticulum. Although a diversity of organelle-specific fluorescent stains have been commercially available, our efforts place an emphasis on improvements in terms of low cytotoxicity, high photostability, near-infrared (NIR) emission, two-photon excitation, and long fluorescence lifetimes, which are crucial for long-time tracking of biological processes, tissue and body imaging with deep penetration and low autofluorescence, and time-resolved fluorescence imaging. Research on fluorescent probes with both analyte responsiveness and organelle targetability is a new and emerging area that has attracted increasing attention over the

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past few years. We have extended the diversity by developing organelle-specific responsive probes capable of detecting changes in biomolecular levels (reactive oxygen species, fluoride ion, hydrogen sulfide, zinc cation, thiol-containing amino acids, and cyclooxygenase-2) and the microenvironment (viscosity, polarity, and pH). Future research should give more considerations of the "low-concern" organelles, such as the Golgi apparatus, the endoplasmic reticulum, and ribosomes. In addition, given the tiny sizes of subcellular organelles (20-1000 nm), we anticipate that clearer visulization of the cellular events within specific organelles will rely on super-resolution optical microscopy with nanoscopic-scale resolution

(52) Boudreau TF, Peck GM, O'Keefe SF, Stewart AC. The Interactive Effect of Fungicide Residues and Yeast Assimilable Nitrogen on Fermentation Kinetics and Hydrogen Sulfide Production during Cider Fermentation. J Sci Food Agric 2016 Oct 16. Abstract: BACKGROUND: Fungicide residues on fruit may adversely affect yeast during cider fermentation, leading to sluggish or stuck fermentation or the production of hydrogen sulfide (H2 S), an undesirable aroma compound. This phenomenon has been studied in grape fermentation, but not in apple fermentation. Low nitrogen availability, characteristic of apples, may further exacerbate the effects of fungicides on yeast during fermentation. This study explored the effects of three fungicides: elemental sulfur (S0 ), (known to result in increased H2 S in wine), fenbuconazole (used in orchards but not vineyards); and fludioxonil (used in post-harvest storage of apples). RESULTS: Only S0 led to increased H2 S production. Fenbuconazole (>/=0.2 mg L-1 ) resulted in decreased fermentation rate and increased residual sugar. An interactive effect of yeast assimilable nitrogen (YAN) concentration and fenbuconazole was observed, whereby increasing YAN concentration alleviated the negative effects of fenbuconazole on fermentation kinetics. CONCLUSIONS: Cidermakers should be aware that residual fenbuconazole (as low as 0.2 mg L-1 ) in apple juice may lead to stuck fermentation, especially when YAN concentration is below 250 mg L-1 . These results indicate that fermentation problems attributed to low YAN may be caused or exacerbated by additional factors such as fungicide residues, which have greater impact on fermentation performance under low YAN conditions

(53) Lobb I, Jiang J, Lian D, Liu W, Haig A, Saha MN, et al. Hydrogen sulfide protects renal grafts against prolonged cold ischemia-reperfusion injury via specific mitochondrial actions. Am J Transplant 2016 Oct 15. Abstract: Ischemia-reperfusion injury (IRI) is unavoidably caused by loss and subsequent restoration of blood flow during organ procurement and prolonged IRI results in increased rates of delayed graft function and early graft loss. The endogenously produced gasotransmitter, hydrogen sulfide (H2 S), is a novel molecule that mitigates hypoxic tissue injury. The current study investigates the protective mitochondrial effects of H2 S during in vivo cold storage and subsequent renal transplantation (RTx) and in vitro cold hypoxic renal injury. Donor allografts from Brown Norway rats treated with University of Wisconsin (UW) solution + H2 S (150 muM NaSH) during prolonged (24-hour) cold (4 degrees C) storage exhibited significantly (p<0.05) decreased acute necrotic/apoptotic injury and significantly (p<0.05) improved function and recipient Lewis rat survival compared to UW solution alone. Treatment of rat kidney epithelial cells (NRK-52E) with the mitochondrial-targeted H2 S donor, AP39, during in vitro cold hypoxic injury improved the protective capacity of H2 S >1000-fold compared to similar levels of the non-specific H2 S donor, GYY4137 and also improved syngraft function and survival following prolonged cold storage compared to UW. H2 S treatment mitigates cold IRI-associated renal injury via mitochondrial actions and could represent a novel therapeutic strategy to minimize the detrimental clinical outcomes of prolonged cold IRI during RTx. This article is protected by copyright. All rights reserved

(54) Nabeshima Y, Onozuka D, Kitazono T, Hagihara A. Analysis of Japanese Articles about Suicides Involving Charcoal Burning or Hydrogen Sulfide Gas. Int J Environ Res Public

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Health 2016 Oct 15;13(10). Abstract: It is well known that certain types of media reports about suicide can result in imitative suicides. In the last two decades, Japan has experienced two suicide epidemics and the subsequent excessive media coverage of these events. However, the quality of the media suicide reports has yet to be evaluated in terms of the guidelines for media suicide coverage. Thus, the present study analyzed Japanese newspaper articles (n = 4007) on suicides by charcoal burning or hydrogen sulfide gas between 11 February 2003 and 13 March 2010. The suicide reports were evaluated in terms of the extent to which they conformed to the suicide reporting guidelines. The mean violation scores were 3.06 (+/-0.7) for all articles, 3.2 (+/-0.8) for articles about suicide by charcoal burning, and 2.9 (+/-0.7) for articles about suicide by hydrogen sulfide (p < 0.001). With the exception of not following several recommendations, newspaper articles about suicide have improved in quality, as defined by the recommendations for media suicide coverage. To prevent imitative suicides based on media suicide reports, individuals in the media should try not to report suicide methods and to make attempts to report the poor condition of suicide survivors

(55) Ahmad A, Gero D, Olah G, Szabo C. Effect of endotoxemia in mice genetically deficient in cystathionine-gamma-lyase, cystathionine-beta-synthase or 3-mercaptopyruvate sulfurtransferase. Int J Mol Med 2016 Oct 14. Abstract: Hydrogen sulfide (H2S) has been proposed to exert pro- as well as anti-inflammatory effects in various models of critical illness. In this study, we compared bacterial lipopolysaccharide (LPS)induced changes in inflammatory mediator production, indices of multiple organ injury and survival in wildtype (WT) mice and in mice with reduced expression of one of the three H2Sproducing enzymes, cystathionine-gamma-lyase (CSE), cystathionine-beta-synthase (CBS) or 3-mercaptopyruvate sulfurtransferase (3MST). Mice were injected intraperitoneally (i.p.) with LPS (10 mg/kg). After 6 h, the animals were sacrificed, blood and organs were collected and the following parameters were evaluated: blood urea nitrogen (BUN) levels in blood, myeloperoxidase (MPO) and malondialdehyde (MDA) in the lung, cytokine levels in plasma and the expression of the three H2Sproducing enzymes (CBS, CSE and 3MST) in the spleen, lung, liver and kidney. LPS induced a tissuedependent upregulation of some of the H2Sproducing enzymes in WT mice (upregulation of CBS in the spleen, upregulation of 3MST in the liver and upregulation of CBS, CSE and 3MST in the lung). Moreover, LPS impaired glomerular function, as evidenced by increased BUN levels. Renal impairment was comparable in the CSE/ and Delta3MST mice after LPS challenge; however, it was attenuated in the CBS+/ mice. MPO levels (an index of neutrophil infiltration) and MDA levels (an index of oxidative stress) in lung homogenates were significantly increased in response to LPS; these effects were similar in the WT, CBS+/, CSE/ and Delta3MST mice; however, the MDA levels tended to be lower in the CBS+/ and CSE/ mice. LPS induced significant increases in the plasma levels of multiple cytokines [tumor necrosis factor (TNF)alpha, interleukin (IL)1beta, IL6, IL10, IL12 and interferon (IFN)gamma] in plasma; TNFalpha, IL10 and IL12 levels tended to be lower in all three groups of animals expressing lower levels of H2Sproducing enzymes. The survival rates after the LPS challenge did not show any significant differences between the four animal groups tested. Thus, the findings of this study indicate that a deficiency in 3MST does not significantly affect endotoxemia, while a deficiency in CBS or CSE slightly ameliorates the outcome of LPS-induced endotoxemia in vivo

(56) Yuan Y, Karahan HE, Yildirim C, Wei L, Birer O, Zhai S, et al. "Smart poisoning" of Co/SiO2 catalysts by sulfidation for chirality-selective synthesis of (9,8) single-walled carbon nanotubes. Nanoscale 2016 Oct 14;8(40):17705-13. Abstract: The chirality-selective synthesis of relatively large (diameter > 1 nm) single-walled carbon nanotubes (SWCNTs) is of great interest for a variety of practical applications, but only a few catalysts are available so far. Previous studies suggested that S (compounds) can enhance the chirality-selectivity of Co catalysts in SWCNT

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synthesis, however, the mechanism behind is not fully understood, and no tailorable methodology has yet been developed. Here, we demonstrate a facile approach to achieve the chirality-selective synthesis of SWCNTs by the sulfidation-based poisoning of silica-supported Co catalysts using a mixture of H2S and H2. The UV-vis-NIR, photoluminescence, and Raman spectroscopy results together show that the resulting SWCNTs have a narrow diameter distribution of around 1.2 nm, and (9,8) nanotubes have an abundance of approximately 38% among the semiconducting species. More importantly, the carbon yield achieved by the sulfided catalyst (2.5 wt%) is similar to that of the nonsulfided one (2.7 wt%). The characterization of the catalysts by X-ray diffraction, X-ray photoelectron spectroscopy, X-ray fluorescence, and H2 temperature-programmed reduction shows that the sulfidation leads to the formation of Co9S8 nanoparticles. However, Co9S8 nanoparticles are reduced back to regenerate metallic Co nanoparticles during the synthesis of SWCNTs, which maintain a high carbon yield. In this process, Co9S8 nanoparticles seemingly intermediate the production of Co nanoparticles with narrow size distribution. Due to the fact that the poisoning step improves the quality of the end-product rather than hampering the growth process, we have coined the process developed as "smart poisoning". This study not only reveals the mechanism behind the beneficial role of S in the selective synthesis of relatively large SWCNTs but also presents a promising method to create chirality-selective catalysts with high activity for scalable synthesis

(57) Kaur G, Padiya R, Adela R, Putcha UK, Reddy GS, Reddy BR, et al. Garlic and Resveratrol Attenuate Diabetic Complications, Loss of beta-Cells, Pancreatic and Hepatic Oxidative Stress in Streptozotocin-Induced Diabetic Rats. Front Pharmacol 2016;7:360. Abstract: The study was aimed at finding the effect of garlic and resveratrol on loss of beta-cells and diabetic complication in streptozotocin (STZ)-induced Type-I diabetic rats. Rats were injected with single dose STZ (50 mg/kg, i.p.) for induction of type 1 diabetes (Dia) and compared with control group. Rats from third (Dia+Gar), fourth (Dia+Resv), and fifth (Dia+Met) groups were fed raw garlic homogenate (250 mg/kg/day), resveratrol (25 mg/kg/day), and metformin (500 mg/kg/day) orally, respectively, for a period of 4 weeks. Diabetic group had decreased serum insulin and hydrogen sulfide levels along with increased blood glucose and glycated hemoglobin, triglyceride, uric acid, and nitric oxide levels. Significant (p < 0.05) increase in pancreatic and hepatic TBARS, conjugated dienes, nitric oxide, and AGE level and significant (p < 0.05) decrease in SOD, catalase, H2S, GSH level were observed in diabetic group. Administration of garlic, resveratrol, and metformin significantly (p < 0.05) normalized most of the altered metabolic and oxidative stress parameters as well as histopathological changes. Administration of garlic, resveratrol, and metformin in diabetic rat decreases pancreatic beta-cell damage and hepatic injury. Our data concluded that administration of garlic showed more promising effect in terms of reducing oxidative stress and pathological changes when compared to resveratrol and metformin groups

(58) Wang M, Hu Y, Fan Y, Guo Y, Chen F, Chen S, et al. Involvement of Hydrogen Sulfide in Endothelium-Derived Relaxing Factor-Mediated Responses in Rat Cerebral Arteries. J Vasc Res 2016 Oct 13;53(3-4):172-85. Abstract: BACKGROUND/AIM: H2S is a novel vasoactivator. To verify the hypothesis that H2S may act as an endothelium-derived hyperpolarizing factor (EDHF) in the rat cerebrovasculature, the role of H2S in endothelium-derived relaxing factor (EDRF)-mediated responses was investigated. METHODS: Cystathionine-gamma-lyase (CSE) was knocked down with an siRNA technique. Artery diameter, hyperpolarization and Ca2+-activated K+ (KCa) current were measured. RESULTS: CSE knockdown was indicated by a decrease in protein and mRNA expression in the rat middle cerebral artery (MCA) and cerebral basilar artery (CBA). Acetylcholine (ACh) induced significant hyperpolarization and vasodilation in endothelium-intact MCA and CBA. Removal of the endothelium abolished these responses. The nitric oxide (NO) synthase inhibitor L-NAME, but not the PGI2 production inhibitor indomethacin, significantly inhibited ACh-

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induced hyperpolarization and vasodilation in the CBA. In the presence of L-NAME and indomethacin, ACh-induced hyperpolarization and vasodilation in the MCA and CBA were attenuated. The non-NO/PGI2-mediated responses were abolished by the KCa channel blockers charybdotoxin and apamin. In the cerebral arteries from the CSE knockdown rat, non-NO/PGI2-mediated responses were significantly attenuated, and the remaining responses were abolished by charybdotoxin and apamin or the CSE inhibitor propargylglycine. CSE knockdown did not affect L-NAME-sensitive responses in the CBA. Sodium hydrosulfide (NaHS) augmented the KCa current in CBA vascular smooth muscle cells. CONCLUSION: EDHF-mediated responses in rat cerebral arteries were due to H2S activating the KCa channel

(59) Tian B, Qiao Z, Zhang L, Li H, Pei Y. Hydrogen sulfide and proline cooperate to alleviate cadmium stress in foxtail millet seedlings. Plant Physiol Biochem 2016 Oct 13;109:293-9. Abstract: Hydrogen sulfide (H2S) and some functional amino acids in crops have been involved in the defense system against heavy-metal pollution. Here we report the relationships and functions of H2S and proline to cadmium (Cd) stress. Sodium hydrosulfide (NaHS) pretreatment decreased the electrolytic leakage and the malondialdehyde and hydrogen peroxide contents while enhancing photosynthesis in Cd-treated seedlings. Furthermore, pretreatment with NaHS markedly exacerbated Cd-induced alterations in proline content, the activities of proline-5-carboxylate reductase (P5CR) and proline dehydrogenase (PDH), and the transcript levels of P5CR and PDH. When endogenous H2S was scavenged or inhibited by various H2S modulators, the Cd-induced increase in endogenous proline was weakened. Combined pretreatment with H2S and proline was moderately higher in the Cd-stressed growth status, stomata movements and oxidative damage of seedlings compared to a single treatment with H2S or proline. These results suggest that H2S and proline cooperate to alleviate Cd-damage in foxtail millet

(60) Aenishaenslin C, Bouchard C, Koffi JK, Ogden NH. Exposure and preventive behaviours toward ticks and Lyme disease in Canada: Results from a first national survey. Ticks Tick Borne Dis 2016 Oct 13. Abstract: Lyme disease (LD) risk is increasing in Canada. In 2014, the government of Canada launched a national communication campaign to raise awareness and promote the adoption of individual preventive behaviours toward ticks and LD. The objectives of this study were to evaluate and compare the adoption of LD preventive behaviours and the exposure to tick bites of Canadians in the five main targeted regions (British Columbia, Prairie provinces, Ontario, Quebec and the Atlantic provinces). A national survey was conducted in December 2014 (n=2876) to collect data on LD awareness, behaviours and risk factors. Overall, the proportion of respondents reporting tick exposure was high (20%). The results suggest that even though LD awareness was found to be high (with only 12% of the respondents reporting that they never heard about LD), less than half of the Canadians who heard about it have adopted specific preventive behaviours toward tick bites, such as regular tick checks (reported by 52%), protective clothing (50%), using tick repellent (41%) or shower or bath (41%) after visiting a wooded area in a LD risk area. Moreover, significant differences were found between regions, gender, age groups and dog ownership status, regarding preventive behaviours and factors of exposure. A high level of knowledge of Lyme disease, living in the Prairie region, as well as having found a tick on oneself or a relative, were found to be associated with the adoption of preventive behaviours. This study underlines the importance to take into account specific regional characteristics of risk and to maintain public health communication efforts through time in order to increase the adoption of preventive behaviours of Canadians

(61) Yalcin YD, Aydin M, Hocaoglu PT, Koraltan M, Ozdemir H, Kotil T, et al. Ultrastructural changes in epithelial cells of rats exposed to low concentration of hydrogen sulfide for 50 Days. Ultrastruct Pathol 2016 Oct 13;1-7.

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Abstract: Hydrogen sulfide (H2S) and other volatile sulfur compounds (VSCs) appear mainly in the oral air of patients with halitosis. It seems that VSCs are directly involved in the pathogenesis of gingival diseases. In previous studies, short-term (7 hours-4 days), high concentrations (5-400 ppm) of H2S applications on periodontal tissues have been evaluated in a culture medium. The aim of the present study was to investigate the potential effects of lower (equivalent to halitosis) concentrations of H2S on rat gingival tissue for longer-term inhalation. The threshold level of pathologic halitosis perceived by humans at 250 ppb of H2S was converted to rat equivalent concentration (4.15 ppm). Rats in the experimental (H2S) group (n=8) were exposed to H2S continuously but not the control rats (n=8). After 50 days, the gingival sulcular tissue samples of each rat were taken and examined using transmission electron microscope. Ultrastructural changes in the sulcular epithelia of the rat gingiva showed deformation of celullar shape, vacuolization, and disintegrity of intercelullar connection by loss of desmosomes and collagen fibrils. No basal membrane damage was observed. Inhalation of low levels of H2S (equivalent of halitosis) in the oral environment causes ultrastructural celullar damages in rat sulcular mucosa. These results suggest that halitosis may be the potential reason for periodontal destruction in humans

(62) Yao Y, Kong C, Yin L, Jain AD, Ratia K, Thatcher GR, et al. Time-gated detection of cystathionine gamma-lyase activity and inhibition with a selective, luminogenic hydrogen sulfide sensor. Chemistry 2016 Oct 12. Abstract: Herein, we report the design, synthesis and characterization of a lanthanide(III) complex-based probe for the time-gated luminescence detection of hydrogen sulfide (H(2)S) in aqueous media. The probe's unique sensing mechanism relies on the selective reduction of azide to amine by sulfide, followed by intramolecular cyclization to form a quinolinone. The quinolinone is a sensitizer that absorbs near-UV light and transfers excitation energy to coordinated Tb(III) or Eu(III) ions to trigger a strong "turn-on" luminescence response with ms-scale lifetimes characteristic of lanthanide complexes. Using this probe, we developed a robust, high throughput screening (HTS) assay for detecting H(2)S generated by cystathionine gamma-lyase (CSE), one of the main producers of H(2)S in mammalian cells. In a 240-compound screen to identify potential CSE inhibitors, the Eu(III) analog of the sensor showed a low false positive rate and high Z'-factor (> 0.7)

(63) Ciocci M, Iorio E, Carotenuto F, Khashoggi HA, Nanni F, Melino S. H2S-releasing nanoemulsions: a new formulation to inhibit tumor cells proliferation and improve tissue repair. Oncotarget 2016 Oct 12. Abstract: The improvement of solubility and/or dissolution rate of poorly soluble natural compounds is an ideal strategy to make them optimal candidates as new potential drugs. Accordingly, the allyl sulfur compounds and omega-3 fatty acids are natural hydrophobic compounds that exhibit two important combined properties: cardiovascular protection and antitumor activity. Here, we have synthesized and characterized a novel formulation of diallyl disulfide (DADS) and alpha-linolenic acid (ALA) as protein-nanoemulsions (BAD-NEs), using ultrasounds. BAD-NEs are stable over time at room temperature and show antioxidant and radical scavenging property. These NEs are also optimal H2S slow-release donors and show a significant anti-proliferative effect on different human cancer cell lines: MCF-7 breast cancer and HuT 78 T-cell lymphoma cells. BAD-NEs are able to regulate the ERK1/2 pathway, inducing apoptosis and cell cycle arrest at the G0/G1 phase. We have also investigated their effect on cell proliferation of human adult stem/progenitor cells. Interestingly, BAD-NEs are able to improve the Lin- Sca1+ human cardiac progenitor cells (hCPC) proliferation. This stem cell growth stimulation is combined with the expression and activation of proteins involved in tissue-repair, such as P-AKT, alpha-sma and connexin 43. Altogether, our results suggest that these antioxidant nanoemulsions might have potential application in selective cancer therapy and for promoting the muscle tissue repair

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(64) Sanokawa-Akakura R, Akakura S, Tabibzadeh S. Replicative Senescence in Human Fibroblasts Is Delayed by Hydrogen Sulfide in a NAMPT/SIRT1 Dependent Manner. PLoS One 2016;11(10):e0164710. Abstract: Recent evidence suggests that hydrogen sulfide (H2S) has cytoprotective and anti-aging effects. However, the mechanisms for such properties are not fully understood. Here, we show that the expression of the main H2S producing enzyme, CBS, and production of H2S are coordinately diminished in replicative senescent adult human dermal fibroblasts. The reduced production of H2S falls within the same time-frame that the hallmarks of replicative senescence appear including accumulation of SA-beta-Gal, enhanced expression of p16, p21, and RRM2B while the expression of RRM2, hTERT, SIRT1, NAMPT, and NAD/NADH ratio all fall. Exogenous H2S increases the expression of hTERT, NAMPT, SIRT1 and NAD/NADH ratio in treated cells. Moreover, H2S safeguards the expression of hTERT in a NAMPT and SIRT1 dependent manner and delays the onset of replicative senescence as evidenced by reduced accumulation of age associated SA-beta-Gal and cessation of proliferation. Postponement of loss of cell proliferative capacity without risk of mutagenesis shows implications for use of H2S in delaying the adverse effects of senescence in organisms

(65) Zhuang R, Lou Y, Qiu X, Zhao Y, Qian D, Yan X, et al. Identification of a yeast strain able to oxidize and remove sulfide high efficiently. Appl Microbiol Biotechnol 2016 Oct 10. Abstract: Hydrogen sulfide is a common odor gas of volatile sulfur-containing compound. The emission of hydrogen sulfide in the waste gas from industrial processing and agricultural operations could cause air pollution to the surrounding environment. The aim of this study was screening and isolation of wild yeast strains from the sludge of sewage pool in the fishmeal processing plant to remove hydrogen sulfide odor. A yeast strain ZJY-7 was obtained. Its hydrogen sulfide removal efficiency was 97.1 %. The morphology studies were investigated using microscope and scanning electron microscope. The yeast isolate was then identified by biochemical tests using API 20 C AUX strip and sequencing 26S rDNA genes. Both biochemical tests analysis and the molecular identification indicated that the yeast isolate ZJY-7 was Candida tropicalis ZJY-7. The NCBI GenBank accession number is KX259479. Batch tests showed that the yeast strain tolerated up to 300 mg/l of dissolved S2- concentration. The yeast also tolerated a wide pH range (2.5-9.0). The optimal initial sulfide concentration of C. tropicalis ZJY-7 on sulfide oxidation and sulfate generation was 200 mg/l, and at initial pH value 6. The highest accumulated sulfate was 91.8 mg/l at 48 h. These results broadened the range of sulfide-oxidizing organism and new application of C. tropicalis on the control of hydrogen sulfide odor pollution. The yeast may have potential to be used in bioreactor for removal of hydrogen sulfide gas

(66) Garcia-Perez T, Le BS, Revah S. Ozone and hydrogen peroxide as strategies to control biomass in a trickling filter to treat methanol and hydrogen sulfide under acidic conditions. Appl Microbiol Biotechnol 2016 Oct 8. Abstract: The operation and performance of a biotrickling filter for methanol (MeOH) and hydrogen sulfide (H2S) removal at acid pH was studied. Excess biomass in the filter bed, causing performance loss and high pressure drop, was controlled by intermittent addition, of ozone (O3) and hydrogen peroxide (H2O2). The results showed that after adaptation to acid pH, the maximum elimination capacity (EC) reached for MeOH was 565 g m-3 h -1 (97 % RE). High MeOH loads resulted in increased biomass concentration within the support, triggering reductions in the removal efficiency (RE) for both compounds close to 50 %, and high pressure drop. At this stage, an inlet load of 150.2 +/- 16.7 g m-3 h-1 of O3 was fed by 38 days favoring biomass detachment, and EC recovery and lower pressure dropped with a maximum elimination capacity of 587 g m-3 h-1 (81 % RE) and 15.8 g m-3 h-1 (97 % RE) for MeOH and H2S, respectively. After O3 addition, a rapid increase in biomass content and higher fluctuations in pressure drop were observed reducing the system performance. A second treatment with oxidants was implemented feeding a O3 load of 4.8 +/- 0.1 g m-3 h-1 for 7 days, followed by H2O2 addition for 23

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days, registering 607.5 gbiomass L-1packing before and 367.5 gbiomass L-1packing after the oxidant addition. PCR-DGGE analysis of different operating stages showed a clear change in the bacterial populations when O3 was present while the fungal population was less affected

(67) Fiorucci S, Zampella A, Cirino G, Bucci M, Distrutti E. Decoding the vasoregulatory activities of bile acid activated receptors in systemic and portal circulation. Role for gaseous mediators. Am J Physiol Heart Circ Physiol 2016 Oct 7;ajpheart. Abstract: Bile acids are end product of cholesterol metabolism generated in the liver and released in the intestine. In addition to their role in nutrient absorption, bile acids are increasingly recognized as regulatory signals which exert their function beyond the intestine by activating a network of membrane and nuclear receptors. The best characterized of these bile acid activated receptors, GPBAR1 (also known as TGR5) and the Farnesosid-x-receptor (FXR) have also been detected in the vascular system and their activation mediate the vasodilatory effects of bile acids in the systemic and splanchnic circulation. GPBAR1, is a G protein coupled receptor, that is preferentially activated by lithocholic acid (LCA) a secondary bile acid. GPBAR1 is expressed in endothelial cells and liver sinusoidal cells (LSEC), and respond to LCA by regulating the expression of both endothelial nitric oxide synthase (eNOS) and cystathionine-gamma-liase (CSE), an enzyme involved in generation of hydrogen sulfide (H2S). Activation of CSE by GPBAR1 ligands in LSEC is due to genomic and non-genomic effects, involves protein phosphorylation, and leads to release of H2S. Despite specie-specific effects have been described, vasodilation caused by GPBAR1 ligands in the liver microcirculation and aortic rings is abrogated by inhibition of CSE but not by eNOS inhibitor. Vasodilation caused by GPBAR1 (and FXR) ligands also involves large conductance calcium activated potassium channels likely acting downstream to H2S. The identification of GPBAR1 as a vasodilatory receptor is of relevance in the treatment of complex disorders including metabolic syndrome-associated diseases, liver steatohepatitis and portal hypertension

(68) Naik JS, Osmond JM, Walker BR, Kanagy NL. Hydrogen Sulfide-Induced Vasodilation Mediated by Endothelial TRPV4 Channels. Am J Physiol Heart Circ Physiol 2016 Oct 7;ajpheart. Abstract: Hydrogen sulfide (H2S) is a recently described gaseous vasodilator produced within the vasculature by the enzymes cystathionine gamma-lyase and 3-mercaptopyruvate sulfurtansferase. Previous data demonstrate that endothelial cells (EC) are the source of endogenous H2S production and are required for H2S-induced dilation. However, the signal transduction pathway activated by H2S within EC has not been elucidated. TRPV4 and large conductance Ca2+-activated K channels (BK channels) are expressed in EC. H2S-induced dilation is inhibited by luminal administration of iberiotoxin and disruption of the endothelium. Calcium influx through TRPV4 may activate these endothelial BK channels (eBK). We hypothesized that H2S-mediated vasodilation involves activation of TPRV4 within the endothelium. In pressurized, phenylephrine-constricted mesenteric arteries, H2S elicited a dose-dependent vasodilation blocked by inhibition of TRPV4 channels (GSK2193874A, 300 nM). H2S (1 muM) increased TRPV4-dependent (1.8 fold) localized calcium events in EC of pressurized arteries loaded with Fluo-4 and Oregon Green. In pressurized EC tubes, H2S (1 microM) and the TRPV4 activator, GSK101679A (30 nM) increased calcium events 1.8 and 1.5 fold, respectively. H2S-induced an iberiotoxin-sensitive outward current measured using whole-cell patch clamp techniques in freshly dispersed EC. H2S increased K+ currents from 10 pA/pF to 30 pA/pF at +150 mV. Treatment with Na2S increased the level of sulfhydration of TRPV4 channels in aortic ECs. These results demonstrate that H2S-mediated vasodilation involves activation of TRPV4-dependent Ca2+ influx and BK channel activation within EC. Activation of TRPV4 channels appears to cause calcium events that result in the opening of eBK channels, endothelial hyperpolarization, and subsequent vasodilation

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(69) Powell CR, Foster JC, Okyere B, Theus MH, Matson JB. Therapeutic Delivery of H2S via COS: Small Molecule and Polymeric Donors with Benign Byproducts. J Am Chem Soc 2016 Oct 7. Abstract: Carbonyl sulfide (COS) is a gas that may play important roles in mammalian and bacterial biology, but its study is limited by a lack of suitable donor molecules. We report here the use of N-thiocarboxyanhydrides (NTAs) as COS donors that release the gas in a sustained manner under biologically relevant conditions with innocuous peptide byproducts. Carbonic anhydrase converts COS into H2S, allowing NTAs to serve as either COS or H2S donors, depending on the availability of the enzyme. Analysis of the pseudo-first-order H2S release rate under biologically relevant conditions revealed a release half-life of 75 min for the small molecule NTA under investigation. A polynorbornene bearing pendant NTAs made by ring-opening metathesis polymerization was also synthesized to generate a polymeric COS/H2S donor. A half-life of 280 min was measured for the polymeric donor. Endothelial cell proliferation studies revealed an enhanced rate of proliferation for cells treated with the NTA over untreated controls

(70) He M, Liu X, Lu X, Zhang C, Wang R. Structures and Acidity Constants of Silver-Sulfide Complexes in Hydrothermal Fluids: A First Principles Molecular Dynamics Study. J Phys Chem A 2016 Oct 6. Abstract: In order to quantify the speciation and structures of silver-sulfide complexes in aqueous solutions, we have carried out systematic first principles molecular dynamics (FPMD) simulations at three temperatures (25 degrees C, 200 degrees C, and 300 degrees C). It is found that mono-sulfide (i.e., Ag(HS)) and di-sulfide species (i.e., Ag(HS)2-) are the major silver-sulfide species over a wide T-P range, while Ag(HS)32- can hold stably only at ambient temperatures and Ag(HS)43- does not exist even at the ambient conditions. Ag(H2S)+ has a tetrahedral structure up to 300 degrees C (i.e., Ag(H2S)(H2O)3+). Ag(H2S)2+ remains 4-coordinated to 200 degrees C (i.e., Ag(H2S)2(H2O)2+) but it transforms to 3-coordinate at 300 degrees C (i.e., Ag(H2S)2(H2O)+). All of the other mono- and di-sulfide species (Ag(HS)(H2O)0, Ag(HS)(OH)-, Ag(HS)(H2S)0, Ag(HS)2- and AgS(HS)2-) have two-fold linear structures. For their solvation structures, the H2S ligands donate weak H-bonds to water O; the HS- ligands accept weak H-bonds from water H; the dangling S2- form strong H-bonds with H of water molecules and the OH- ligands can form strong H-bonds as donors and weak H-bonds as acceptors. We further calculated the acidity constants (i.e. pKas) of Ag(H2S)+ and Ag(H2S)2+ complexes using FPMD based vertical energy gap method. Based on the calculated pKas, the mono- and di-sulfide species distributions versus pH have been derived. We found that for mono-sulfide species, Ag(HS)(H2O)0 is the major species in near neutral pH, while Ag(H2S)(H2O)3+ and Ag(HS)(OH)- exist in the acid and alkaline pH range at T<=200 degrees C, respectively. At 300 degrees C, both Ag(HS)(OH)- and Ag(HS)(H2O)0 are dominant in the neutral pH range, and Ag(H2S)(H2O)2+ only exists in acidic solutions. For di-sulfide species, Ag(HS)2- is dominative in near neutral pH condition at the three temperatures; Ag(HS)(H2S)0 stays in mild acidic pH range only at 25 degrees C; AgS(HS)2- and Ag(H2S)2(H2O)2+ (Ag(H2S)2(H2O)+ at 300 degrees C) are trivial at the three conditions. The results of structures and acidity constants provide quantitative and microscopic basis for understanding the behavior of silver complexes in hydrothermal fluids

(71) Corvino A, Severino B, Fiorino F, Frecentese F, Magli E, Perissutti E, et al. Fragment-based de novo design of a cystathionine gamma-lyase selective inhibitor blocking hydrogen sulfide production. Sci Rep 2016 Oct 6;6:34398. Abstract: Hydrogen sulfide is an essential catabolite that intervenes in the pathophysiology of several diseases from hypertension to stroke, diabetes and pancreatitis. It is endogenously synthesized mainly by two pyridoxal-5'-phosphate-dependent enzymes involved in L-cysteine metabolism: cystathionine-ss-synthase (CBS) and cystathionine-gamma-lyase (CSE). Research in this field is currently impaired by the lack of pharmacological tools such as selective enzymatic inhibitors that could target

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specifically only one of these pathways. We used a novel approach based on a hybrid method that includes drug design, synthetic biology, metabolomics and pharmacological assays to rationally design a new inhibitor selective for the CSE enzyme. The identification of this compound opens new frontiers towards a better understanding of the role of CSE over CBS in the pathophysiology of diseases where a role for the H2S pathway has been proposed and the development of new lead compounds that could target the CSE enzyme

(72) van den Born JC, Mencke R, Conroy S, Zeebregts CJ, van GH, Hillebrands JL. Cystathionine gamma-lyase is expressed in human atherosclerotic plaque microvessels and is involved in micro-angiogenesis. Sci Rep 2016 Oct 6;6:34608. Abstract: Atherosclerotic plaques are classically divided into stable and vulnerable plaques. Vulnerable plaques are prone to rupture with a risk for infarction. High intraplaque microvessel density predisposes to plaque vulnerability. Hydrogen sulfide (H2S) is a proangiogenic gasotransmitter which is endogenously produced by cystathionine gamma-lyase (CSE), and is believed to have vasculoprotective effects. However, due to its proangiogenic effects, H2S may result in pathological angiogenesis in atherosclerotic plaques, thereby increasing plaque vulnerability. The aim of this study was to determine CSE expression pattern in atherosclerotic plaques, and investigate whether CSE is involved in micro-angiogenesis in vitro. Endarterectomy plaques were studied for CSE expression, and the role of CSE in micro-angiogenesis was studied in vitro. CSE is expressed in plaques with similar levels in both stable and vulnerable plaques. CSE co-localized with von Willebrand Factor-positive microvessel endothelial cells and alpha-smooth-muscle actin-positive SMCs. In vitro, inhibition of CSE in HMEC-1 reduced tube formation, cell viability/proliferation, and migration which was restored after culture in the presence of H2S donor GYY4137. CSE is expressed in intraplaque microvessels, and H2S is a stimulator of micro-angiogenesis in vitro. Due to this pro-angiogenic effect, high levels of CSE in atherosclerotic plaques may be a potential risk for plaque vulnerability

(73) Ranjithkumar A, Durga J, Ramesh R, Rose C, Muralidharan C. Cleaner processing: a sulphide-free approach for depilation of skins. Environ Sci Pollut Res Int 2016 Oct 5. Abstract: The conventional unhairing process in leather making utilises large amount of lime and sodium sulphide which is hazardous and poses serious waste disposal concerns. Under acidic conditions, sodium sulphide liberates significant quantities of hydrogen sulphide which causes frequent fatal accidents. Further, the conventional unhairing process involves destruction of the hair leading to increased levels of biological oxygen demand (BOD), chemical oxygen demand (COD), total dissolved solids (TDS) and total suspended solids (TSS) in the effluent. A safe approach is needed to overcome such environmental and health problems through an eco-benign process. The present study deals with a clean technology in which the keratinous body is detached from the dermis using enzymes produced from Bacillus crolab MTCC 5468 by solid state fermentation (SSF) as an alternative to noxious chemicals. Complete unhairing of skin could be achieved with an enzyme concentration of 1.2 % (w/w). The bio-chemical parameters of the spent liquor of the enzymatic process were environmentally favourable when compared with conventional method. The study indicates that the enzymatic unhairing is a safe process which could be used effectively in leather processing to alleviate pollution and health problems

(74) Floris SD, Talbot JJ, Wilkinson MJ, Herr JD, Steele RP. Quantum molecular motion in the mixed ion-radical complex, [(H2O)(H2S)]. Phys Chem Chem Phys 2016 Oct 5;18(39):27450-9. Abstract: The cation dimer of water and hydrogen sulfide, [(H2O)(H2S)]+, serves as a fundamental model for the oxidation chemistry of H2S. The known oxidative metabolism of H2S by biological species in sulfur-rich environments has motivated the study of the inherent properties of this benchmark complex, with possible mechanistic implications for

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modern water oxidation chemistry. The low-energy isomer of this open-shell ion is a proton-transferred (PT) structure, H3O+SH . An alternative PT structure, H3S+OH , and a hemibonded (HB) isomer, [H2O.SH2]+, are also stable isomers, placing this complex intermediate to known (H2O)2+ (PT) and (H2S)2+ (HB) limiting regimes. This intermediate character suggested the possibility of unique molecular motion, even in the vibrational ground state. Path integral molecular dynamics and anharmonic vibrational spectroscopy simulations have been performed in this study, in order to understand the inherent quantum molecular motion of this complex. The resulting structural distributions were found to deviate significantly from both classical and harmonic analyses, including the observation of large-amplitude anharmonic motion of the central proton and nearly free rotation of the terminal hydrogens. The predicted vibrational spectra are particularly unique and suggest characteristic signatures of the strong electronic interactions and anharmonic vibrational mode couplings in this radical cation

(75) Dugbartey GJ, Peppone LJ, de G, I. An integrative view of cisplatin-induced renal and cardiac toxicities: Molecular mechanisms, current treatment challenges and potential protective measures. Toxicology 2016 Oct 4;371:58-66. Abstract: Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell's antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies including combination therapy with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide

(76) Fernandes VS, Hernandez M. The Role of Nitric Oxide and Hydrogen Sulfide in Urinary Tract Function. Basic Clin Pharmacol Toxicol 2016 Oct;119 Suppl 3:34-41. Abstract: This MiniReview focuses on the role played by nitric oxide (NO) and hydrogen sulfide (H2 S) in physiology of the upper and lower urinary tract. NO and H2 S, together with carbon monoxide, belong to the group of gaseous autocrine/paracrine messengers or gasotransmitters, which are employed for intra- and intercellular communication in almost all organ systems. Because they are lipid-soluble gases, gaseous transmitters are not constrained by cellular membranes, so that their storage in vesicles for later release is not possible. Gasotransmitter signals are terminated by falling concentrations upon reduction in production that are caused by reacting with cellular components (essentially reactive oxygen species and NO), binding to cellular components or diffusing away. NO and, more recently, H2 S have been identified as key mediators in neurotransmission of the urinary tract, involved in the regulation of ureteral smooth muscle activity and urinary flow ureteral resistance, as well as by playing a crucial role in the smooth muscle relaxation of bladder outlet region. Urinary bladder function is also dependent on integration of inhibitory mediators, such as NO, released from the urothelium. In the bladder base and distal ureter, the co-localization of neuronal NO synthase with substance P and calcitonin gene-related peptide in sensory nerves as well as the existence of a high nicotinamide adenine dinucleotide phosphate-diaphorase activity in dorsal root ganglion neurons also suggests the involvement of NO as a sensory neurotransmitter

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(77) Lin Y, Chen Y, Zhu N, Zhao S, Fan J, Liu E. Hydrogen sulfide inhibits development of atherosclerosis through up-regulating protein S-nitrosylation. Biomed Pharmacother 2016 Oct;83:466-76. Abstract: Hydrogen sulfide (H2S) is an important gaseous signaling molecule that serves many important regulatory roles in physiological and pathophysiological conditions. H2S exerts an anti-atherosclerotic effect through mediating the biological functions of nitric oxide (NO). However, its mechanism of action is unclear. The purpose of this study is to explore the effect mechanism of H2S on the development of atherosclerosis with regard to protein S-nitrosylation. A total of 45 male apoE-/- mice were randomly divided into three groups. Atherosclerosis was induced by Western diet (21% fat and 0.15% cholesterol) with/without administration of a H2S donor (NaHS) or an endogenous cystathionine gamma-lyase inhibitor (d, l-propargylglycine) for 12 weeks. After 12 weeks, plasma lipid and plasma NO levels were measured. Aortic gross lesion area and histopathological features of aortic lesion were determined. Additionally, the level of S-nitrosylated proteins in vascular smooth muscle cells (VSMCs) was detected using immunofluorescence in aorta. Rat VSMCs were performed in an in vitro experiment. Inducible nitric oxide synthase (iNOS) protein expression, NO generation, protein S-nitrosylation, and cell proliferation and migration were measured. We found that H2S significantly reduced the aortic atherosclerotic lesion area (P=0.006) and inhibited lipid and macrophage accumulation (P=0.004, P=0.002) and VSMC proliferation (P=0.019) in apoE-/- mice. H2S could up-regulate levels of plasma NO and protein S-nitrosylation in aorta VSMCs. However, d, l- propargylglycine had the opposite effect, increasing the lesion area and the content of lipids and macrophages in the lesions of apoE-/- mice and down-regulating plasma NO levels and protein S-nitrosylation in aorta VSMCs. In vitro experiments, H2S could significantly reverse the reduction of iNOS expression and NO generation induced by oxidized low-density lipoprotein in VSMCs. Moreover, H2S could increase the protein S-nitrosylation level of VSMCs in a dose-dependent manner, and the effect could be inhibited by iNOS inhibitors. In addition, proliferation and migration of VSMCs could be inhibited by H2S in a dose-dependent manner, which could be blocked by an iNOS inhibitor or protein S-nitrosylation removal agent. Our data suggest that H2S could inhibit the development of atherosclerosis by up-regulating plasma NO and protein S-nitrosylation, thereby inhibiting the proliferation and migration of VSMCs

(78) Bolden C, King SB, Kim-Shapiro DB. Reactions between nitrosopersulfide and heme proteins. Free Radic Biol Med 2016 Oct;99:418-25. Abstract: When nitrosothiols react with excess hydrogen sulfide, H2S, they form several intermediates including nitrosopersulfide (SSNO-). The stability and importance of this species has been debated. While some data suggest

(79) Kabe Y, Yamamoto T, Kajimura M, Sugiura Y, Koike I, Ohmura M, et al. Cystathionine beta-synthase and PGRMC1 as CO sensors. Free Radic Biol Med 2016 Oct;99:333-44. Abstract: Heme oxygenase (HO) is a mono-oxygenase utilizing heme and molecular oxygen (O2) as substrates to generate biliverdin-IXalpha and carbon monoxide (CO). HO-1 is inducible under stress conditions, while HO-2 is constitutive. A balance between heme and CO was shown to regulate cell death and survival in many experimental models. However, direct molecular targets to which CO binds to regulate cellular functions remained to be fully examined. We have revealed novel roles of CO-responsive proteins, cystathionine beta-synthase (CBS) and progesterone receptor membrane component 1 (PGRMC1), in regulating cellular functions. CBS possesses a prosthetic heme that allows CO binding to inhibit the enzyme activity and to regulate H2S generation and/or protein arginine methylation. On the other hand, in response to heme accumulation in cells, PGRMC1 forms a stable dimer through stacking interactions of two protruding heme molecules. Heme-mediated PGRMC1 dimerization is necessary to interact with EGF receptor and cytochromes P450 that determine cell proliferation and xenobiotic metabolism. Furthermore, CO interferes with PGRMC1 dimerization by dissociating the heme stacking, and thus results in modulation of cell responses. This

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article reviews the intriguing functions of these two proteins in response to inducible and constitutive levels of CO with their pathophysiological implications

(80) Taylor CE. A novel treatment for "morning sickness": Nausea of pregnancy could be induced by excess sulfite which molybdenum can help alleviate. Med Hypotheses 2016 Oct;95:31-3. Abstract: Nausea and vomiting of pregnancy (NVP) remains difficult to treat. Last century, thalidomide was used to alleviate NVP, but it caused teratogenesis by interfering with angiogenesis. The gasotransmitters hydrogen sulfide (H2S) and nitric oxide are mutually dependent on each other for their angiogenesis-related functions. Pregnancy-related requirements for increased endogenous H2S could create a temporary excess of sulfite, an H2S catabolite, which is toxic and can induce nausea. Sulfite oxidase, a molybdenum-containing enzyme, catalyzes oxidation of sulfite to sulfate, which can then be excreted or reused by the body. Supplementation with molybdenum should facilitate enhanced sulfite oxidase activity, thus lowering gestationally-elevated sulfite levels in the gastrointestinal tract and easing NVP

(81) Yuan S, Pardue S, Shen X, Alexander JS, Orr AW, Kevil CG. Hydrogen sulfide metabolism regulates endothelial solute barrier function. Redox Biol 2016 Oct;9:157-66. Abstract: Hydrogen sulfide (H2S) is an important gaseous signaling molecule in the cardiovascular system. In addition to free H2S, H2S can be oxidized to polysulfide which can be biologically active. Since the impact of H2S on endothelial solute barrier function is not known, we sought to determine whether H2S and its various metabolites affect endothelial permeability. In vitro permeability was evaluated using albumin flux and transendothelial electrical resistance. Different H2S donors were used to examine the effects of exogenous H2S. To evaluate the role of endogenous H2S, mouse aortic endothelial cells (MAECs) were isolated from wild type mice and mice lacking cystathionine gamma-lyase (CSE), a predominant source of H2S in endothelial cells. In vivo permeability was evaluated using the Miles assay. We observed that polysulfide donors induced rapid albumin flux across endothelium. Comparatively, free sulfide donors increased permeability only with higher concentrations and at later time points. Increased solute permeability was associated with disruption of endothelial junction proteins claudin 5 and VE-cadherin, along with enhanced actin stress fiber formation. Importantly, sulfide donors that increase permeability elicited a preferential increase in polysulfide levels within endothelium. Similarly, CSE deficient MAECs showed enhanced solute barrier function along with reduced endogenous bound sulfane sulfur. CSE siRNA knockdown also enhanced endothelial junction structures with increased claudin 5 protein expression. In vivo, CSE genetic deficiency significantly blunted VEGF induced hyperpermeability revealing an important role of the enzyme for barrier function. In summary, endothelial solute permeability is critically regulated via exogenous and endogenous sulfide bioavailability with a prominent role of polysulfides

(82) Cuevasanta E, Moller MN, Alvarez B. Biological chemistry of hydrogen sulfide and persulfides. Arch Biochem Biophys 2016 Sep 30. Abstract: Hydrogen sulfide (H2S) has been traditionally considered to be a toxic molecule for mammals. However, it can be formed endogenously and exert physiological effects with potential health benefits. H2S can partition two-fold in biological membranes and traverse them rapidly, diffusing between compartments. H2S reactivity has similarities to that of thiols, although it is less nucleophilic than thiols and it can form different products. H2S can react with oxidants derived from the partial reduction of oxygen, but direct scavenging is unlikely to explain H2S protective actions. Important effects are exerted on mitochondria including the stimulation or the inhibition of the electron transport chain. Possible mechanisms for unleashing biological consequences are the reactions with metal centers and with thiol oxidation products. The reactions of H2S with disulfides (RSSR) and sulfenic acids (RSOH) lead to the formation of persulfides (RSSH). Persulfides have enhanced nucleophilicity with respect to the corresponding thiol,

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consistent with the alpha effect. Besides, the inner and outer sulfurs can both act as electrophiles. In this review, we describe the reactions of H2S with oxidized thiol products and the properties of the persulfides formed in the context of the chemical biology of H2S

(83) Mikami Y, Kakizawa S, Yamazawa T. Essential Roles of Natural Products and Gaseous Mediators on Neuronal Cell Death or Survival. Int J Mol Sci 2016 Sep 29;17(10). Abstract: Although precise cellular and molecular mechanisms underlying neurodegeneration still remain enigmatic, key factors associated with degenerative disorders, such as glutamate toxicity and oxidative stress, have been recently identified. Accordingly, there has been growing interest in examining the effects of exogenous and endogenous molecules on neuroprotection and neurodegeneration. In this paper, we review recent studies on neuroprotective and/or neurodegenerative effects of natural products, such as caffeic acid and chlorogenic acid, and gaseous mediators, including hydrogen sulfide and nitric oxide. Furthermore, possible molecular mechanisms of these molecules in relation to glutamate signals are discussed. Insight into the pathophysiological role of these molecules will make progress in our understanding of molecular mechanisms underlying neurodegenerative diseases, and is expected to lead to potential therapeutic approaches

(84) Gao B, Cui L, Pan Y, Xue M, Zhu B, Zhang G, et al. A highly selective fluorescent probe based on Michael addition for fast detection of hydrogen sulfide. Spectrochim Acta A Mol Biomol Spectrosc 2016 Sep 28;173:457-61. Abstract: A new 4-hydroxy-1,8-naphthalimide-based compound (probe 1) has been designed and synthesized. The colorimetric and fluorescent properties of probe 1 towards hydrogen sulfide (H2S) were investigated in detail. The results show that the probe 1 could selectively and sensitively recognize H2S rather than other reactive sulfur species. The reaction mechanism of this probe is an intramolecular cyclization caused by the Michael addition of H2S to give 4-hydroxy-1,8-naphthalimide. The intramolecular charge transfer of 4-hydroxy-1,8-naphthalimide is significant. Probe 1 quickly responded to H2S and showed a 75-fold fluorescence enhancement in 5min. Moreover, probe 1 could detect H2S quantitatively with a detection limit as low as 0.23muM

(85) DeMartino AW, Zigler DF, Fukuto JM, Ford PC. Carbon disulfide. Just toxic or also bioregulatory and/or therapeutic? Chem Soc Rev 2016 Sep 27. Abstract: The overview presented here has the goal of examining whether carbon disulfide (CS2) may play a role as an endogenously generated bioregulator and/or has therapeutic value. The neuro- and reproductive system toxicity of CS2 has been documented from its long-term use in the viscose rayon industry. CS2 is also used in the production of dithiocarbamates (DTCs), which are potent fungicides and pesticides, thus raising concern that CS2 may be an environmental toxin. However, DTCs also have recognized medicinal use in the treatment of heavy metal poisonings as well as having potency for reducing inflammation. Three known small molecule bioregulators (SMBs) nitric oxide, carbon monoxide, and hydrogen sulfide were initially viewed as environmental toxins. Yet each is now recognized as having intricate, though not fully elucidated, biological functions at concentration regimes far lower than the toxic doses. The literature also implies that the mammalian chemical biology of CS2 has broader implications from inflammatory states to the gut microbiome. On these bases, we suggest that the very nature of CS2 poisoning may be related to interrupting or overwhelming relevant regulatory or signaling process(es), much like other SMBs

(86) Deng YF, Liu YY, Zhang YT, Wang Y, Liang JB, Tufarelli V, et al. Efficacy and role of inulin in mitigation of enteric sulfur-containing odor in pigs. J Sci Food Agric 2016 Sep 24. Abstract: BACKGROUND: The efficacy and role of inulin in the mitigation of enteric sulfur-containing odor gases hydrogen sulfide (H2 S) and methyl mercaptan (CH3 SH) in pigs were examined in this study. Twelve Duroc x Landrace x Yorkshire male finisher pigs (60.7 +/- 1.9 kg), housed individually in open-circuit respiration chambers, were

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randomly assigned to two dietary groups, namely basal diet (control) and basal diet supplemented with 1% (w/w) inulin. At the end of the 45 day experiment, pigs were slaughtered and volatile fatty acid (VFA) concentration, sulfate radical (

(87) Chiu TW, Chen YL, Wu CY, Yu PL, Shieh YH, Huang B. Hydrogen Sulfide Modulates the S-Nitrosoproteome and the Mitochondrial Morphology in Endothelial Cells. Acta Cardiol Sin 2016 Sep;32(5):604-11. Abstract: BACKGROUND: Hydrogen sulfide (H2S) is one of the endogenous gaseous molecules promoting the production of nitric oxide (NO) which has cardioprotective functions. However, the role of the H2S-mediated protein S-nitrosoproteome and its subsequent physiological response remains unclear. METHODS: Endothelial cells EAhy 926 were treated with 50 muM of H2S for 2 hours. The NO bound S-nitrosoproteins were purified by a biotin-switch and then digested by trypsin. Resulting peptides from control and H2S treatment were separately labeled by isobaric tag for relative and absolute quantitation 114/115, quantified by liquid chromatography tandem-mass spectrometry and analyzed by ingenuity pathway analysis (IPA) software. The microP software was applied to analyze the morphological changes of mitochondria. RESULTS: With the treatment of H2S, 416 S-nitrosylated proteins were identified. IPA analysis showed that these proteins were involved in five signaling pathways. The NO-bound cysteine residues and the S-nitrosylation levels (115/114) were shown for ten S-nitrosoproteins. Western blot further verified the S-nitrosylation of thioredoxin-dependant peroxide reductase, cytochrome c oxidase and cytochrome b-c1 complex that are involved in the mitochondrial signaling pathway. H2O2-induced mitochondrial swelling can be reduced by the pretreatment of H2S. CONCLUSIONS: The H2S-mediated endothelial S-nitrosoproteome has been confirmed. In the present study, we have proposed the cardioprotective role of H2S via maintaining mitochondrial homeostasis

(88) Lalou S, Capece A, Mantzouridou FT, Romano P, Tsimidou MZ. Implementing principles of traditional concentrated grape must fermentation to the production of new generation balsamic vinegars. Starter selection and effectiveness. J Food Sci Technol 2016 Sep;53(9):3424-36. Abstract: In an effort to implement principles of traditional concentrated grape must fermentation to the production of new generation balsamic vinegars (BVs), the specific goals of the study were the isolation and molecular identification of the predominant yeasts in concentrated grape must (cv. Xinomavro), their technological characterization and the evaluation of the fermentative aptitude of the selected strains. Tolerance against 5-hydroxymethyl-furfural (HMF) and furfural, acetic acid and glucose concentration was examined by appropriate methods and tests. The enological characteristics studied were acetic acid and H2S production, foaming and flocculation ability and key enzymatic activity. PCR-RFLP analysis revealed only the presence of Saccharomyces cerevisiae and Hanseniaspora uvarum among the 14 predominant osmophilic yeast isolates. Tolerance to both HMF and furfural was found strain- and dose-dependent and was suggested as a critical factor in the pre-selection of yeast starters. The most tolerant yeasts to these stress factors, a S. cerevisiae and a non-Saccharomyces strains, showed satisfactory growth in the presence of high glucose and acetic acid content (up to 600 g/L and 2 % w/w, respectively) and desirable enological characteristics. Results from the comparative evaluation of the fermentative aptitude of these strains with a commercial wine strain highlighted that the isolates had glucophilic behaviour and ability to produce desirable amounts of ethanol (100-120 g/kg) in short time (~20 d). The key volatiles useful for varietal discrimination and differentiation between the BVs and the traditional ones were also evaluated

(89) Wang B, Sun Q, Li Y, Li P, Xia W, Liu D, et al. OS 12-04 TAURINE SUPPLEMENTATION LOWERS BLOOD PRESSURE AND REDUCES CAROTID INTIMA-MEDIA THICKNESS IN PREHYPERTENSION. J Hypertens 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e76-e77.

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Abstract: OBJECTIVE: Taurine, the most abundant, semiessential, sulfur-containing amino acid, is well known to improve metabolic status in animal models. However, no rigorous clinical trial has validated whether this beneficial effect of taurine occurs in human, especially in prehypertensive participants. DESIGN AND METHOD: In this randomized, double-blind, placebo-controlled study, we assessed the effects of taurine intervention on metabolic parameters, such as blood pressure (BP) levels, carotid intima-media thickness (IMT), ankle brachial index (ABI)/toe brachial index (TBI), BMI and biochemical parameters in prehypertensive participants. We randomly assigned 120 eligible prehypertensive individuals to receive either taurine supplementation (1.6 g per day) or a placebo for 12 weeks. Then we further validated the results in spontaneously hypertensive rats (SHR), which were were intervented with 2% taurine water for 12 weeks. RESULTS: Totally 97 participants completed the trial and no significant difference observed between the taurine and placebo groups. Taurine supplementation significantly decreased the clinic and 24-hour ambulatory BPs, especially in those with high-normal BP. In addition, taurine supplementation significantly improved endothelium-dependent and -independent vasodilation and reduced IMTs of these prehypertensive participants. Meanwhile taurine intervention increased plasma H2S and taurine concentrations. Other parameters did not change significantly upon taurine treatment compared with pre-treatment or placebo group. To further elucidate the mechanism, experimental studies were performed both in vivo and in vitro. The results showed that taurine treatment exerts hypotensive effects by upregulating the expressions of H2S-synthesizing enzymes and reducing agonist-induced vascular reactivity through the inhibition of TRPC3-mediated calcium influx in human and mouse mesenteric arteries. Also, taurine reduced ROS levels and improved mitochondrial respiratory fucntions in VSMCs from SHR compared with control group, thus inhibiting vascular remodeling pathways. CONCLUSIONS: Taurine supplementation improved vascular function of prehypertensive participants and SHRs by lowering BP levels and reducing IMT values. Taurine may become a new dietary factor improving the metabolic status in prehypertension

(90) de Moor JM, Aiuppa A, Avard G, Wehrmann H, Dunbar N, Muller C, et al. Turmoil at Turrialba Volcano (Costa Rica): Degassing and eruptive processes inferred from high-frequency gas monitoring. J Geophys Res Solid Earth 2016 Aug;121(8):5761-75. Abstract: Eruptive activity at Turrialba Volcano (Costa Rica) has escalated significantly since 2014, causing airport and school closures in the capital city of San Jose. Whether or not new magma is involved in the current unrest seems probable but remains a matter of debate as ash deposits are dominated by hydrothermal material. Here we use high-frequency gas monitoring to track the behavior of the volcano between 2014 and 2015 and to decipher magmatic versus hydrothermal contributions to the eruptions. Pulses of deeply derived CO2-rich gas (CO2/Stotal > 4.5) precede explosive activity, providing a clear precursor to eruptive periods that occurs up to 2 weeks before eruptions, which are accompanied by shallowly derived sulfur-rich magmatic gas emissions. Degassing modeling suggests that the deep magmatic reservoir is ~8-10 km deep, whereas the shallow magmatic gas source is at ~3-5 km. Two cycles of degassing and eruption are observed, each attributed to pulses of magma ascending through the deep reservoir to shallow crustal levels. The magmatic degassing signals were overprinted by a fluid contribution from the shallow hydrothermal system, modifying the gas compositions, contributing volatiles to the emissions, and reflecting complex processes of scrubbing, displacement, and volatilization. H2S/SO2 varies over 2 orders of magnitude through the monitoring period and demonstrates that the first eruptive episode involved hydrothermal gases, whereas the second did not. Massive degassing (>3000 T/d SO2 and H2S/SO2 > 1) followed, suggesting boiling off of the hydrothermal system. The gas emissions show a remarkable shift to purely magmatic composition (H2S/SO2 < 0.05) during the second eruptive period, reflecting the depletion of the hydrothermal system or the establishment of high-temperature conduits bypassing remnant hydrothermal reservoirs, and the transition from phreatic to phreatomagmatic eruptive activity

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(91) Cacanyiova S, Berenyiova A, Kristek F, Drobna M, Ondrias K, Grman M. The adaptive role of nitric oxide and hydrogen sulphide in vasoactive responses of thoracic aorta is triggered already in young spontaneously hypertensive rats. J Physiol Pharmacol 2016 Aug;67(4):501-12. Abstract: The aorta plays an important role in blood pressure control so the early determination of its vasoactive properties could predict pathological changes in hypertension. The aim of study was to compare vasoactive properties and geometry of thoracic aorta (TA) and the participation of two vasoactive transmitters, nitric oxide (NO) and hydrogen sulphide (H2S), in TA tone regulation in young Wistar rats (WR) and spontaneously hypertensive rats (SHR). Four-weeks-old WR and SHR were used. Systolic blood pressure (sBP) was measured by plethysmography. The vasoactivity of TA was evaluated by changes in isometric tension. For morphological study the geometry of TA was measured using light microscopy. Decomposition of NO donor (nitrosoglutathione, GSNO) induced by H2S donor (Na2S) was studied by UV-VIS spectroscopy. In SHR the sBP was not increased in spite of cardiac hypertrophy compared to WR. Vasoconstriction to noradrenaline (NA) was decreased in SHR compared to WR which correlated with arterial wall hypotrophy. Acetylcholine (Ach)-induced vasorelaxation was increased and NO component participated in vasorelaxation and basal tone regulation significantly more in SHR. Na2S induced biphasic effect in both experimental groups, however, the shift towards vasorelaxation was demonstrated in SHR. Pretreatment with NO-synthase inhibitor, NG-nitro-L-arginine methylester (L-NAME), diminished the contractile part of vasoactive Na2S effects in both strains, moreover, an increased sensitivity in behalf of vasorelaxation was observed in SHR. Pretreatment with Na2S did not affect Ach-induced vasorelaxation in WR, but an inhibition was demonstrated in SHR. On the other hand, pretreatment with Na2S increased the release of NO from GSNO which corresponded with increased GSNO-induced vasorelaxation in both groups. However, this effect was stronger in SHR. The study showed that TA of prehypertensive SHR disposed by decreased contractility and strengthened endothelium-regulated vasorelaxant mechanisms involving of NO and H2S interaction which could serve as adaptive mechanisms in the adulthood

(92) Sugahara S, Suzuki M, Kamiya H, Yamamuro M, Semura H, Senga Y, et al. Colorimetric Determination of Sulfide in Microsamples. Anal Sci 2016;32(10):1129-31. Abstract: A method for determination of hydrogen sulfide in microsamples (200 muL) was developed by modifying the methylene blue method. Samples were collected using a micropipette and were combined with sulfide coloring reagent and 5 mL of 0.1 M HCl in test tubes. Absorbance of the solution was measured spectrophotometrically at 667 nm. This modified method did not require any special labware or technique, and can be used in a variety of research fields

(93) Zhang X, Yu L, Wu X, Hu W. Experimental Sensing and Density Functional Theory Study of H2S and SOF2 Adsorption on Au-Modified Graphene. Adv Sci (Weinh ) 2015 Nov;2(11):1500101. Abstract: A gas sensor is used to detect SF6 decomposed gases, which are related to insulation faults, to accurately assess the insulated status of electrical equipment. Graphene films (GrF) modified with Au nanoparticles are used as an adsorbent for the detection of H2S and SOF2, which are two characteristic products of SF6 decomposed gases. Sensing experiments are conducted at room temperature. Results demonstrate that Au-modified GrF yields opposite responses to the tested gases and is thus considered a promising material for developing H2S- and SOF2-selective sensors. The first-principles approach is applied to simulate the interaction between the gases and Au-modified GrF systems and to interpret experimental data. The observed opposite resistance responses can be attributed to the charge-transfer differences related to the interfacial interaction between the gases and systems. The density of states and Mulliken population analysis results confirm the apparent charge transfer in Au-modified GrF chemisorption, whereas the van der Waals effect dominates the pristine graphene

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adsorption systems. Calculation results can also explicate the significant SOF2 responses on Au-modified GrF. This work is important in graphene modulation and device design for selective detection