Acido solfidrico nella letteratura internazionale

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Acido solfidrico nella letteratura internazionale Studi inseriti in PubMed nel mese di dicembre 2014 (aggiornamento al 9 gennaio 2015) (1) Ervin KM. Anchoring the Gas-Phase Acidity Scale from Hydrogen Sulfide to Pyrrole. Experimental Bond Dissociation Energies of Nitromethane, Ethanethiol, and Cyclopentadiene. J Phys Chem A 2014 Dec 29. Abstract: A meta-analysis of experimental information from a variety of sources is combined with statistical thermodynamics calculations to refine the gas-phase acidity scale from hydrogen sulfide to pyrrole. The absolute acidities of hydrogen sulfide, methanethiol, and pyrrole are evaluated from literature R-H bond energies and radical electron affinities to anchor the scale. Relative acidities from proton transfer equilibrium experiments are used in a local thermochemical network optimized by least-squares analysis to obtain absolute acidities of 14 additional acids in the region. Thermal enthalpy and entropy corrections are applied using molecular parameters from density functional theory, with explicit calculation of hindered rotor energy levels for torsional modes. The analysis reduces the uncertainties of the absolute acidities of the 14 acids to within +/-1.2 to +/-3.3 kJ/mol, expressed as estimates of the 95% confidence level. The experimental gas phase acidities are compared with calculations, with generally good agreement. For nitromethane, ethanethiol, and cyclopentadiene, the refined acidities can be combined with electron affinities of the corresponding radicals from photoelectron spectroscopy to obtain improved values of the C-H or S-H bond dissociation energies, yielding D298(H-CH2NO2) = 423.5 +/- 2.2 kJ mol-1, D298(C2H5S-H) = 364.7 +/- 2.2 kJ mol-1, and D298(C5H5-H) = 347.4 +/- 2.2 kJ mol-1. These values represent the best available experimental bond dissociation energies for these species (2) Haouzi P, Chenuel B, Sonobe T. High-dose hydroxocobalamin administered after H2S exposure counteracts sulfide-poisoning-induced cardiac depression in sheep. Clin Toxicol (Phila) 2015 Jan;53(1):28-36. Abstract: Abstract Context. Severe H2S poisoning leads to death by rapid respiratory and cardiac arrest, the latter can occur within seconds or minutes in severe forms of intoxication. Objectives. To determine the time course and the nature of H2S-induced cardiac arrest and the effects of high-dose hydroxocobalamin administered after the end of sulfide exposure. Materials and methods. NaHS was infused in 16 sedated mechanically ventilated sheep to reach concentrations of H2S in the blood, which was previously found to lead to cardiac arrest within minutes following the cessation of H2S exposure. High-dose hydroxocobalamin (5 g) or saline solution was administered intravenously, 1 min after the cessation of NaHS infusion. Results. All animals were still alive at the cessation of H2S exposure. Three animals (18%) presented a cardiac arrest within 90 s and were unable to receive any antidote or vehicle. In the animals that survived long enough to receive either hydroxocobalamin or saline, 71% (5/7) died in the control group by cardiac arrest within 10 min. In all instances, cardiac arrest was the result of a pulseless electrical activity (PEA). In the group that received the antidote, intravenous injection of 5 g of hydroxocobalamin provoked an abrupt increase in blood pressure and blood flow; PEA was prevented in all instances. However, we could not find any evidence for a recovery in oxidative metabolism in the group receiving hydroxocobalamin, as blood lactate remained elevated and even continued to rise after 1 h, despite restored hemodynamics. This, along with an unaltered recovery of H2S kinetics, suggests that hydroxocobalamin did not act through a mechanism of H2S trapping. Conclusion. In this sheep model, there was a high risk for cardiac arrest, by PEA, persisting up to 10 min after H2S exposure. Very high dose of hydroxocobalamin

Transcript of Acido solfidrico nella letteratura internazionale

Page 1: Acido solfidrico nella letteratura internazionale

Acido solfidrico nella letteratura internazionale Studi inseriti in PubMed nel mese di dicembre 2014

(aggiornamento al 9 gennaio 2015)

(1) Ervin KM. Anchoring the Gas-Phase Acidity Scale from Hydrogen Sulfide to Pyrrole. Experimental Bond Dissociation Energies of Nitromethane, Ethanethiol, and Cyclopentadiene. J Phys Chem A 2014 Dec 29. Abstract: A meta-analysis of experimental information from a variety of sources is combined with statistical thermodynamics calculations to refine the gas-phase acidity scale from hydrogen sulfide to pyrrole. The absolute acidities of hydrogen sulfide, methanethiol, and pyrrole are evaluated from literature R-H bond energies and radical electron affinities to anchor the scale. Relative acidities from proton transfer equilibrium experiments are used in a local thermochemical network optimized by least-squares analysis to obtain absolute acidities of 14 additional acids in the region. Thermal enthalpy and entropy corrections are applied using molecular parameters from density functional theory, with explicit calculation of hindered rotor energy levels for torsional modes. The analysis reduces the uncertainties of the absolute acidities of the 14 acids to within +/-1.2 to +/-3.3 kJ/mol, expressed as estimates of the 95% confidence level. The experimental gas phase acidities are compared with calculations, with generally good agreement. For nitromethane, ethanethiol, and cyclopentadiene, the refined acidities can be combined with electron affinities of the corresponding radicals from photoelectron spectroscopy to obtain improved values of the C-H or S-H bond dissociation energies, yielding D298(H-CH2NO2) = 423.5 +/- 2.2 kJ mol-1, D298(C2H5S-H) = 364.7 +/- 2.2 kJ mol-1, and D298(C5H5-H) = 347.4 +/- 2.2 kJ mol-1. These values represent the best available experimental bond dissociation energies for these species

(2) Haouzi P, Chenuel B, Sonobe T. High-dose hydroxocobalamin administered after H2S exposure counteracts sulfide-poisoning-induced cardiac depression in sheep. Clin Toxicol (Phila) 2015 Jan;53(1):28-36. Abstract: Abstract Context. Severe H2S poisoning leads to death by rapid respiratory and cardiac arrest, the latter can occur within seconds or minutes in severe forms of intoxication. Objectives. To determine the time course and the nature of H2S-induced cardiac arrest and the effects of high-dose hydroxocobalamin administered after the end of sulfide exposure. Materials and methods. NaHS was infused in 16 sedated mechanically ventilated sheep to reach concentrations of H2S in the blood, which was previously found to lead to cardiac arrest within minutes following the cessation of H2S exposure. High-dose hydroxocobalamin (5 g) or saline solution was administered intravenously, 1 min after the cessation of NaHS infusion. Results. All animals were still alive at the cessation of H2S exposure. Three animals (18%) presented a cardiac arrest within 90 s and were unable to receive any antidote or vehicle. In the animals that survived long enough to receive either hydroxocobalamin or saline, 71% (5/7) died in the control group by cardiac arrest within 10 min. In all instances, cardiac arrest was the result of a pulseless electrical activity (PEA). In the group that received the antidote, intravenous injection of 5 g of hydroxocobalamin provoked an abrupt increase in blood pressure and blood flow; PEA was prevented in all instances. However, we could not find any evidence for a recovery in oxidative metabolism in the group receiving hydroxocobalamin, as blood lactate remained elevated and even continued to rise after 1 h, despite restored hemodynamics. This, along with an unaltered recovery of H2S kinetics, suggests that hydroxocobalamin did not act through a mechanism of H2S trapping. Conclusion. In this sheep model, there was a high risk for cardiac arrest, by PEA, persisting up to 10 min after H2S exposure. Very high dose of hydroxocobalamin

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(5 g), injected very early after the cessation of H2S exposure, improved cardiac contractility and prevented PEA

(3) Lednev IK. Hydrogen Sulfide Inhibits Amyloid Formation. J Phys Chem B 2014 Dec 29. Abstract: Amyloid fibrils are large aggregates of misfolded proteins, which are often associated with various neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and vascular dementia. The amount of hydrogen sulfide (H2S) is known to be significantly reduced in the brain tissue of people diagnosed with Alzheimer's disease relative to that of healthy individuals. These findings prompted us to investigate the effects of H2S on the formation of amyloids in vitro using a model fibrillogenic protein Hen Egg White Lysozyme (HEWL). HEWL forms typical beta-sheet rich fibrils during the course of 70 minutes at low pH and high temperatures. The addition of H2S completely inhibits the formation of beta-sheet and amyloid fibrils, as revealed by deep UV resonance Raman (DUVRR) spectroscopy and ThT fluorescence. Non-resonance Raman spectroscopy shows that disulfide bonds undergo significant rearrangements in the presence of H2S. Raman bands corresponding to disulfide (RSSR) vibrational modes in the 550-500 cm-1 spectral range decreases in intensity and is accompanied by the appearance of a new 490 cm-1 band assigned to the trisulfide group (RSSSR) based on the comparison with model compounds. The formation of RSSSR was proven further using a reaction with TCEP reduction agent and LC-MS analysis of the products. Intrinsic tryptophan fluorescence study shows a strong denaturation of HEWL containing trisulfide bonds. The presented evidence indicates that H2S causes the formation of trisulfide bridges, which destabilizes HEWL structure preventing protein fibrillation. As a result, small spherical aggregates of unordered protein form, which exhibit no cytotoxicity by contrast with HEWL fibrils

(4) Sun X, Jiang G, Bond PL, Keller J, Yuan Z. A novel and simple treatment for control of sulfide induced sewer concrete corrosion using free nitrous acid. Water Res 2014 Dec 17;70C:279-87. Abstract: Improved technologies are currently required for mitigating microbially induced concrete corrosion caused by the oxidation of sulfide to sulfuric acid in sewer systems. This study presents a novel strategy for reducing H2S oxidation on concrete surfaces that accommodate an active corrosion biofilm. The strategy aims to reduce biological oxidation of sulfide through treating the corrosion biofilm with free nitrous acid (FNA, i.e. HNO2). Two concrete coupons with active corrosion activity and surface pH of 3.8 +/- 0.3 and 2.7 +/- 0.2 were sprayed with nitrite. For both coupons, the H2S uptake rates were reduced by 84%-92% 15 days after the nitrite spray. No obvious recovery of the H2S uptake rate was observed during the entire experimental period (up to 12 months after the spray), indicating the long-term effectiveness of the FNA treatment in controlling the activity of the corrosion-causing biofilms. Live/Dead staining tests on the microorganisms on the concrete coupon surfaces demonstrated that viable bacterial cells decreased by > 80% 39 h after the nitrite spray, suggesting that biofilm cells were killed by the treatment. Examination of a corrosion layer within a suspended solution, containing the corrosion-causing biofilms, indicated that biological activity (ATP level and ratio of viable bacterial cells) was severely decreased by the treatment, confirming the bactericidal effect of FNA on the microorganisms in the biofilms. While field trials are still required to verify its effectiveness, it has been demonstrated here that the FNA spray is potentially a very cheap and effective strategy to reduce sewer corrosion

(5) Hu Y, Li R, Yang H, Luo H, Chen Z. Sirtuin 6 Is Essential for Sodium Sulfide-mediated Cytoprotective Effect in Ischemia/Reperfusion-Stimulated Brain Endothelial Cells. J Stroke Cerebrovasc Dis 2014 Dec 24. Abstract: BACKGROUND: Our recent data demonstrated that hydrogen sulfide (H2S), the third gaseous transmitter, had a protective effect on stroke. The purpose of this study was to investigate the protective effect of H2S in oxygen glucose deprivation and reperfusion (OGD/R)-stimulated brain endothelial cells and its association with sirtuin 6 (SIRT6). METHODS: Cultured bEnd.3 brain endothelial cells were exposed to OGD/R. The effects of

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sodium sulfide (Na2S, an exogenous H2S donor) on cell death, lactate dehydrogenase release, intracellular reactive oxygen species (ROS) production, superoxide dismutase (SOD) and catalase (CAT) activities, H2S level, cystathionine gamma-lyase (CSE) expression, and sirtuin 6 (SIRT6) expression/activity were tested to elucidate the protective mechanisms of H2S. RESULTS: Application of Na2S concentration dependently reduced OGD/R-induced cell death, accompanying with decreasing intracellular ROS production and increasing activities of SOD and CAT. In addition, Na2S also enhanced H2S level and CSE expression associated with upregulation of SIRT6 expression and activity in OGD/R-stimulated brain endothelial cells, whereas CSE inhibitor DL-propargylglycine further deteriorated the decrease of SIRT6 expression and activity as well as the reduction of H2S level and CSE expression caused by OGD/R. Furthermore, SIRT6 knockdown abolished Na2S-mediated CSE expression and cytoprotection action in OGD/R-stimulated cells. CONCLUSIONS: Na2S protected brain endothelial cells against simulated ischemic injury through SIRT6-dependent mechanisms

(6) Hine C, Harputlugil E, Zhang Y, Ruckenstuhl C, Lee BC, Brace L, et al. Endogenous Hydrogen Sulfide Production Is Essential for Dietary Restriction Benefits. Cell 2014 Dec 23. Abstract: Dietary restriction (DR) without malnutrition encompasses numerous regimens with overlapping benefits including longevity and stress resistance, but unifying nutritional and molecular mechanisms remain elusive. In a mouse model of DR-mediated stress resistance, we found that sulfur amino acid (SAA) restriction increased expression of the transsulfuration pathway (TSP) enzyme cystathionine gamma-lyase (CGL), resulting in increased hydrogen sulfide (H2S) production and protection from hepatic ischemia reperfusion injury. SAA supplementation, mTORC1 activation, or chemical/genetic CGL inhibition reduced H2S production and blocked DR-mediated stress resistance. In vitro, the mitochondrial protein SQR was required for H2S-mediated protection during nutrient/oxygen deprivation. Finally, TSP-dependent H2S production was observed in yeast, worm, fruit fly, and rodent models of DR-mediated longevity. Together, these data are consistent with evolutionary conservation of TSP-mediated H2S as a mediator of DR benefits with broad implications for clinical translation

(7) Cortese-Krott MM, Fernandez BO, Kelm M, Butler AR, Feelisch M. On the chemical biology of the nitrite/sulfide interaction. Nitric Oxide 2014 Dec 23. Abstract: Sulfide (H2S/HS-) has been demonstrated to exert an astounding breadth of biological effects, some of which resemble those of nitric oxide (NO). While the chemistry, biochemistry and potential (patho)physiology of the cross-talk between sulfide and NO has received considerable attention lately, a comparable assessment of the potential biological implications of an interaction between nitrite and sulfide is lacking. This is surprising inasmuch as nitrite is not only a known bioactive oxidation product of NO, but also efficiently converted to S-nitrosothiols in vivo; the latter have been shown to rapidly react with sulfide in vitro, leading to formation of S/N-hybrid species including thionitrite (SNO-) and nitrosopersulfide (SSNO-). Moreover, nitrite is used as a potent remedy against sulfide poisoning in the clinic. The chemistry of interaction between nitrite and sulfide or related bioactive metabolites including polysulfides and elemental sulfur has been extensively studied in the past, yet much of this information appears to have been forgotten. In this review, we focus on the potential chemical biology of the interaction between nitrite and sulfide or sulfane sulfur molecules, calling attention to the fundamental chemical properties and reactivity of either species and discuss its possible contribution to the biology, pharmacology and toxicology of both nitrite and sulfide

(8) Liu Z, Stromberg D, Liu X, Liao W, Liu Y. A new multiple-stage electrocoagulation process on anaerobic digestion effluent to simultaneously reclaim water and clean up biogas. J Hazard Mater 2014 Oct 15;285C:483-90. Abstract: A new multiple-stage treatment process was developed via integrating electrocoagulation with biogas pumping to simultaneously reclaim anaerobic digestion effluent and clean up biogas. The 1st stage of electrocoagulation treatment under the

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preferred reaction condition led to removal efficiencies of 30%, 81%, 37% and >99.9% for total solids, chemical oxygen demand, total nitrogen and total phosphorus, respectively. Raw biogas was then used as a reactant and pumped into the effluent to simultaneously neutralize pH of the effluent and remove H2S in the biogas. The 2nd stage of electrocoagulation treatment on the neutralized effluent showed that under the selected reaction condition, additional 60% and 10% of turbidity and chemical oxygen demand were further removed. The study concluded a dual-purpose approach for the first time to synergistically combine biogas purification and water reclamation for anaerobic digestion system, which well addresses the downstream challenges of anaerobic digestion technology

(9) Wang P, Isaak CK, Siow YL, O K. Downregulation of cystathionine beta-synthase and cystathionine gamma-lyase expression stimulates inflammation in kidney ischemia-reperfusion injury. Physiol Rep 2014 Dec 1;2(12). Abstract: Inflammation plays a critical role in kidney ischemia-reperfusion injury but mechanisms of increased proinflammatory cytokine expression are not completely understood. Kidney has a high expression of cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) that can synthesize hydrogen sulfide. CBE and CSE are also responsible for the synthesis of cysteine, an essential precursor for glutathione, an antioxidant. Reduced hydrogen sulfide and glutathione production is associated with multiple organ injury. Although pro- and anti-inflammatory effects of hydrogen sulfide have been reported, its role in ischemia-reperfusion-induced inflammation in the kidney has not been well addressed. The aim of this study was to investigate the effect of CBS and CSE-mediated hydrogen sulfide and glutathione production on kidney inflammatory response and the mechanism involved. The left kidney of Sprague-Dawley rat was subjected to 45-min ischemia followed by reperfusion for 24 h. Ischemia-reperfusion caused a significant decrease in CBS and CSE mRNA and protein levels with a concomitant reduction of glutathione and hydrogen sulfide production in the kidney while the expression of proinflammatory cytokine expression (MCP-1, IL-6) was elevated. Hypoxia-reoxygenation of proximal tubular cells led to a decrease in CBS and CSE expression and an increase in proinflammatory cytokine expression. Supplementation of glutathione or hydrogen sulfide donor (NaHS) effectively attenuated cytokine expression in tubular cells. These results suggested that ischemia-reperfusion impaired CBS and CSE-mediated glutathione and hydrogen sulfide production in the kidney, which augmented the expression of proinflammatory cytokines. Regulation of CBS and CSE expression may be therapeutically relevant in alleviating ischemia-reperfusion-induced inflammation and improving kidney function

(10) Laureano-Marin AM, Garcia I, Romero LC, Gotor C. Assessing the transcriptional regulation of L-cysteine desulfhydrase 1 in Arabidopsis thaliana. Front Plant Sci 2014;5:683. Abstract: Hydrogen sulfide is an important signaling molecule that functions as a physiological gasotransmitter of comparable importance to NO and CO in mammalian systems. In plants, numerous studies have shown that sulfide increases tolerance/resistance to stress conditions and regulates essential processes. The endogenous production of hydrogen sulfide in the cytosol of Arabidopsis thaliana occurs by the enzymatic desulfuration of L-cysteine, which is catalyzed by the L-cysteine desulfhydrase enzyme DES1. To define the functional role of DES1 and the role that the sulfide molecule may play in the regulation of physiological processes in plants, we studied the localization of the expression of this gene at the tissue level. Transcriptional data reveal that DES1 is expressed at all developmental stages and is more abundant at the seedling stage and in mature plants. At the tissue level, we analyzed the expression of a GFP reporter gene fused to promoter of DES1. The GFP fluorescent signal was detected in the cytosol of both epidermal and mesophyll cells, including the guard cells. GFP fluorescence was highly abundant around the hydathode pores and inside the trichomes. In mature plants, fluorescence was detected in floral tissues; a strong GFP signal was detected in sepals, petals, and pistils. When siliques were examined, the highest GFP fluorescence

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was observed at the bases of the siliques and the seeds. The location of GFP expression, together with the identification of regulatory elements within the DES1 promoter, suggests that DES1 is hormonally regulated. An increase in DES1 expression in response to ABA was recently demonstrated; in the present work, we observe that in vitro auxin treatment significantly repressed the expression of DES1

(11) Bieza SA, Boubeta F, Feis A, Smulevich G, Estrin DA, Boechi L, et al. Reactivity of Inorganic Sulfide Species toward a Heme Protein Model. Inorg Chem 2014 Dec 24. Abstract: The reactivity of inorganic sulfide species toward heme peptides was explored under biorelevant conditions in order to unravel the molecular details of the reactivity of the endogenous hydrogen sulfide toward heme proteins. Unlike ferric porphyrinates, which are reduced by inorganic sulfide, some heme proteins can form stable FeIII-sulfide adducts. To isolate the protein factors ruling the redox chemistry, we used as a system model, the undecapeptide microperoxidase (MP11), a heme peptide derived from cytochrome c proteolysis that retains the proximal histidine bound to the FeIII atom. Upon addition of gaseous hydrogen sulfide (H2S) at pH 6.8, the UV-vis spectra of MP11 closely resembled those of the low-spin ferric hydroxo complex (only attained at an alkaline pH) and cysteine or alkylthiol derivatives, suggesting that the FeIII reduction was prevented. The low-frequency region of the resonance Raman spectrum revealed the presence of an FeIII-S band at 366 cm-1 and the general features of a low-spin hexacoordinated heme. Anhydrous sodium sulfide (Na2S) was the source of sulfide of choice for the kinetic evaluation of the process. Theoretical calculations showed no distal stabilization mechanisms for bound sulfide species in MP11, highlighting a key role of the proximal histidine for the stabilization of the FeIII-S adducts of heme compounds devoid of distal counterparts, which is significant with regard to the biochemical reactivity of endogenous hydrogen sulfide

(12) Wrobel M, Czubak J, Bronowicka-Adamska P, Jurkowska H, Adamek D, Papla B. Is development of high-grade gliomas sulfur-dependent? Molecules 2014;19(12):21350-62. Abstract: We characterized gamma-cystathionase, rhodanese and 3-mercaptopyruvate sulfurtransferase activities in various regions of human brain (the cortex, thalamus, hypothalamus, hippocampus, cerebellum and subcortical nuclei) and human gliomas with II to IV grade of malignancy (according to the WHO classification). The human brain regions, as compared to human liver, showed low gamma-cystathionase activity. The activity of rhodanese was also much lower and it did not vary significantly between the investigated brain regions. The activity of 3-mercaptopyruvate sulfurtransferase was the highest in the thalamus, hypothalamus and subcortical nuclei and essentially the same level of sulfane sulfur was found in all the investigated brain regions. The investigations demonstrated that the level of sulfane sulfur in gliomas with the highest grades was high in comparison to various human brain regions, and was correlated with a decreased activity of gamma-cystathionase, 3-mercaptopyruvate sulfurtransferase and rhodanese. This can suggest sulfane sulfur accumulation and points to its importance for malignant cell proliferation and tumor growth. In gliomas with the highest grades of malignancy, despite decreased levels of total free cysteine and total free glutathione, a high ratio of GSH/GSSG was maintained, which is important for the process of malignant cells proliferation. A high level of sulfane sulfur and high GSH/GSSG ratio could result in the elevated hydrogen sulfide levels. Because of the disappearance of gamma-cystathionase activity in high-grade gliomas, it seems to be possible that 3-mercaptopyruvate sulfurtransferase could participate in hydrogen sulfide production. The results confirm sulfur dependence of malignant brain tumors

(13) Li H, Feng S, Zhang G, Wang S. Correlation of Lower Concentrations of Hydrogen Sulfide with Atherosclerosis in Chronic Hemodialysis Patients with Diabetic Nephropathy. Blood Purif 2014 Dec 16;38(3-4):188-94. Abstract: Background/Aims: To explore the relationship between hydrogen sulfide (H2S) and uremic accelerated atherosclerosis (UAAS) in chronic hemodialysis patients with

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diabetic nephropathy (CHD/DN). Methods: A total of 36 CHD/DN and 32 chronic hemodialyzed non-diabetic patients with chronic glomerulonephritis (CHD/non-DN) were studied. Plasma H2S was measured with a sulfide sensitive electrode. Results: Plasma H2S in CHD/DN was significantly lower than that in CHD/non-DN patients. Plasma H2S was positively correlated with plasma TGF-beta1, and negatively correlated with MMP-12 in CHD/DN patients. CHD/DN patients exhibited higher CCA-IMT, hsCRP, and lower H2S levels than in CHD/non-DN patients. Moreover, in CHD/DN patients, CCA-IMT was negatively correlated with plasma H2S, and positively correlated with hsCRP and LDL. On multiple regression analysis, H2S levels exhibited independent association with IMT in CHD/DN patients. Conclusions: These findings suggest possible linkage between H2S metabolism and TGF-beta/Smad signaling pathway modulation abnormalities that may contribute to the development of UAAS in CHD/DN patients. (c) 2014 S. Karger AG, Basel

(14) Berenyiova A, Grman M, Mijuskovic A, Stasko A, Misak A, Nagy P, et al. The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants. Nitric Oxide 2014 Dec 18. Abstract: The chemical interaction of sodium sulfide (Na2S) with the NO-donor S-nitrosoglutathione (GSNO) has been described to generate new reaction products, including polysulfides and nitrosopersulfide (SSNO-) via intermediacy of thionitrous acid (HSNO). The aim of the present work was to investigate the vascular effects of the longer-lived products of the Sulfide/GSNO interaction. Here we show that the products of this reaction relax precontracted isolated rings of rat thoracic aorta and mesenteric artery (but to a lesser degree rat uterus) with a >2-fold potency compared with the starting material, GSNO (50 nM), whereas Na2S and polysulfides have little effect at 1-5 microM. The onset of vasorelaxation of the reaction products was 7-10 times faster in aorta and mesenteric arteries compared with GSNO. Relaxation to GSNO (100-500 nM) was blocked by an inhibitor of soluble guanylyl cyclase, ODQ (0.1 and 10 microM), and by the NO scavenger cPTIO (100 microM), but less affected by prior acidification (pH 2-4), and unaffected by N-acetylcysteine (1 mM) or methemoglobin (20 microM heme). By contrast, relaxation to the Sulfide/GSNO reaction products (100-500 nM based on the starting material) was inhibited to a lesser extent by ODQ, only slightly decreased by cPTIO, more markedly inhibited by methemoglobin and N-acetylcysteine, and abolished by acidification before addition to the organ bath. The reaction mixture was found to generate NO as detected by EPR spectroscopy using N-(dithiocarboxy)-N-methyl-D-glucamine (MGD2)-Fe2+ as spin trap. In conclusion, the Sufide/GSNO reaction products are faster and more pronounced vasorelaxants than GSNO itself. We conclude that in addition to NO formation from SSNO-, reaction products other than polysulfides may give rise to nitroxyl (HNO) and be involved in the pronounced relaxation induced by the Sulfide/GSNO cross-talk

(15) Guo Z, Chen G, Zeng G, Li Z, Chen A, Wang J, et al. Fluorescence chemosensors for hydrogen sulfide detection in biological systems. Analyst 2014 Dec 22. Abstract: A comprehensive review of the development of H2S fluorescence-sensing strategies, including sensors based on chemical reactions and fluorescence resonance energy transfer (FRET), is presented. The advantages and disadvantages of fluorescence-sensing strategies are compared with those of traditional methods. Fluorescence chemosensors, especially those used in FRET sensing, are highly promising because of their low cost, technical simplicity, and their use in real-time sulfide imaging in living cells. Potential applications based on sulfate reduction to H2S, the relationship between sulfate-reducing bacteria activity and H2S yield, and real-time detection of sulfate-reducing bacteria activity using fluorescence sensors are described. The current challenges, such as low sensitivity and poor stability, are discussed

(16) Chen W, Niu Y, Jiang W, Tang H, Zhang C, Xia Q, et al. Neuroprotective effects of hydrogen sulfide and the underlying signaling pathways. Rev Neurosci 2014 Dec 22. Abstract: Abstract Hydrogen sulfide (H2S) is an endogenously produced gas that

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represents a novel third gaseous signaling molecule, neurotransmitter and cytoprotectant. Cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE), 3-mercaptopyruvate sulfur transferase with cysteine aminotransferase (3-MST/CAT) and 3-mercaptopyruvate sulfur transferase with d-amino acid oxidase (3-MST/DAO) pathways are involved in the generation of endogenous H2S despite the ubiquitous or restricted distribution of those enzymes. CBS, 3-MST/CAT and 3-MST/DAO can be found in the brain, while CSE is widely located in other organs. There also exist up-taking or recycling and scavenging mechanisms in H2S metabolism to maintain its persistence for physiological function. In recent years, investigating the role that H2S plays in the central nervous system and cardiovascular system has always been a hotspot. To date, effects of H2S are at least partially verified in multiple animal models or neuron cell lines of Alzheimer's disease, Parkinson's disease, cerebral ischemia, major depression disorders and febrile seizure, although subsequent studies are still badly needed. This article presents an overview of current knowledge of H2S focusing on its neuroprotective effects and corresponding signaling pathways, together with connections to potential therapeutic strategies in the clinic

(17) Cordeiro B, Shinn C, Sellke FW, Clements RT. Rottlerin-Induced BKCa Channel Activation Impairs Specific Contractile Responses and Promotes Vasodilation. Ann Thorac Surg 2014 Dec 17. Abstract: BACKGROUND: Activation of large conductance calcium-activated potassium (BKCa) channels is cardioprotective for ischemic injury and can enhance vasorelaxation. Rottlerin has recently been identified as a potent BKCa activator. We demonstrated that rottlerin improves cardiac function and increases coronary flow when used as a cardioplegia additive in rat and mouse models of cardioplegic arrest and reperfusion. In this study we examined the effectiveness and specificity of the putative BKCa activator rottlerin on vascular reactivity in response to specific contractile and dilatory agonists. METHODS: Aortic rings from wild-type (wt) and BKCa knock-out (KO) mice were mounted in a tissue bath with force transducers. The vasodilatory effect of rottlerin was evaluated after pre-constriction with U46619. Dose responses to the contractile agonists U46619 and phenylephrine (PE), and vasodilation responses to rottlerin, hydrogen sulfide (H2S), and sodium nitroprusside (SNP) were performed after pretreatment with rottlerin. Similar studies were performed in pig coronary vessels. RESULTS: The BKCa KO mouse aortic rings exhibited spontaneous contraction and had greater contractile responses to U46619 and reduced vasodilation to SNP compared with wt mice. The wt and KO responses to phenylephrine were similar. Rottlerin dose dependently dilated wild-type vessels, but not in BKCa KO animals. Pretreatment with rottlerin caused depressed U46619 responses, but had no effect on PE, SNP, or H2S-mediated responses. However, pig coronary vessels pretreated with rottlerin exhibited reduced contractile responses and enhanced nitric oxide-dependent dilation. CONCLUSIONS: Rottlerin directly causes vasodilation through BKCa channel dependent mechanisms. The BKCa channel activator pretreatment enhances vasodilatory responses and impairs specific vasoconstrictive agonists

(18) Ma L, Yang L, Zhao J, Wei J, Kong X, Wang C, et al. Comparative proteomic analysis reveals the role of hydrogen sulfide in the adaptation of the alpine plant Lamiophlomis rotata to altitude gradient in the Northern Tibetan Plateau. Planta 2014 Dec 20. Abstract: MAIN CONCLUSION: We found the novel role of hydrogen sulfide in the adaptation of the alpine plant to altitude gradient in the Northern Tibetan Plateau. Alpine plants have developed strategies to survive the extremely cold conditions prevailing at high altitudes; however, the mechanism underlying the evolution of these strategies remains unknown. Hydrogen sulfide (H2S) is an essential messenger that enhances plant tolerance to environmental stress; however, its role in alpine plant adaptation to environmental stress has not been reported until now. In this work, we conducted a comparative proteomics analysis to investigate the dynamic patterns of protein expression in Lamiophlomis rotata plants grown at three different altitudes. We identified and annotated 83 differentially expressed proteins. We found that the levels and enzyme activities of proteins involved in

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H2S biosynthesis markedly increased at higher altitudes, and that H2S accumulation increased. Exogenous H2S application increased antioxidant enzyme activity, which reduced ROS (reactive oxygen species) damage, and GSNOR (S-nitrosoglutathione reductase) activity, which reduced RNS (reactive nitrogen species) damage, and activated the downstream defense response, resulting in protein degradation and proline and sugar accumulation. However, such defense responses could be reversed by applying H2S biosynthesis inhibitors. Based on these findings, we conclude that L. rotata uses multiple strategies to adapt to the alpine stress environment and that H2S plays a central role during this process

(19) Lambert JP, Nicholson CK, Amin H, Amin S, Calvert JW. Hydrogen sulfide provides cardioprotection against myocardial/ischemia reperfusion injury in the diabetic state through the activation of the RISK pathway. Med Gas Res 2014;4(1):20. Abstract: BACKGROUND: Coronary artery disease remains the principal cause of death in patients with diabetes mellitus. Diabetic mice display exacerbated injury following myocardial ischemia-reperfusion (MI/R) and are resistant to most therapeutic interventions. We have reported that sodium sulfide (Na2S) therapy confers cardioprotection during MI/R in non-diabetic mice. Here we tested the hypothesis that Na2S therapy would limit the extent of myocardial injury following MI/R when administered at the time of reperfusion. METHODS AND RESULTS: Diabetic mice (db/db, 12 weeks of age) were subjected to transient myocardial ischemia for a period of 30 minutes followed by reperfusion up to 24 hours. Na2S (0.05 to 1 mg/kg) or saline (vehicle) was administered into the left ventricular lumen at the time of reperfusion. Na2S therapy significantly decreased myocardial injury in the db/db diabetic mouse, as evidenced by a reduction in infarct size and circulating troponin-I levels. The reduction in myocardial injury was also associated with a reduction in oxidative stress and a decrease in cleaved caspase-3 expression. In an effort to evaluate the signaling mechanism responsible for the observed cardioprotection, additional groups of mice were sacrificed during early reperfusion. Hearts were excised and processed for Western blot analysis. These studies revealed that Na2S therapy activated the Erk1/2 arm of the Reperfusion Injury Salvage Kinase (RISK) pathway. CONCLUSION: These findings provide important information that myocardial Erk1/2 activation by Na2S therapy following MI/R sets into motion events, which ultimately lead to cardioprotection in the setting of diabetes

(20) Ried K, Fakler P. Potential of garlic (Allium sativum) in lowering high blood pressure: mechanisms of action and clinical relevance. Integr Blood Press Control 2014;7:71-82. Abstract: Garlic supplements have shown promise in the treatment of uncontrolled hypertension, lowering blood pressure (BP) by about 10 mmHg systolic and 8 mmHg diastolic, similar to standard BP medication. Aged garlic extract, which contains S-allylcysteine as the bioactive sulfur compound, in particular is standardizable and highly tolerable, with little or no known harmful interaction when taken with other BP-reducing or blood-thinning medication. Here we describe biologically plausible mechanisms of garlic's BP-lowering effect. Garlic-derived polysulfides stimulate the production of the vascular gasotransmitter hydrogen sulfide (H2S) and enhance the regulation of endothelial nitric oxide (NO), which induce smooth muscle cell relaxation, vasodilation, and BP reduction. Several dietary and genetic factors influence the efficiency of the H2S and NO signaling pathways and may contribute to the development of hypertension. Sulfur deficiency might play a part in the etiology of hypertension, and could be alleviated with supplementation of organosulfur compounds derived from garlic

(21) Liang M, Jin S, Wu D, Wang M, Zhu Y. Hydrogen sulfide improves glucose metabolism and prevents hypertrophy in cardiomyocytes. Nitric Oxide 2014 Dec 15. Abstract: INTRODUCTION: Hydrogen sulfide (H2S) has been reported to inhibit myocardial hypertrophy in a cell model of cardiomyocyte hypertrophy. Our previous study also shows an H2S-induced increase in glucose metabolism in insulin-targeting cells. The present study aims to examine the hypothesis that H2S attenuates myocardial hypertrophy by

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promoting glucose utilization in cardiomyocytes. METHODS: The cell model of cardiomyocyte hypertrophy was induced by application of phenylephrine and cardiomyocyte hypertrophy was examined using leucine incorporation assay. Protein levels were measured using Western blot analysis. The activity of related enzymes was measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: NaHS (an H2S donor) treatment increased the activity of cultured cardiomyocytes and reduced hypertrophy in cultured cardiomyocytes at concentrations ranging from 25 to 200 micromol/L. NaHS treatment increased glucose uptake and the efficiency of glycolysis and the citric acid cycle. The key enzymes in these reactions, including lactate dehydrogenase and pyruvate kinase and succinate dehydrogenase, were activated by NaHS treatment (100 micromol/L). Some intermediates of glycolysis and the citric acid cycle, including lactic acid, cyclohexylammonium, oxaloacetic acid, succinate, L-dimalate, sodium citrate, cis-aconitic acid, ketoglutarate and DL-isocitric acid trisodium also showed anti-hypertrophic effects in cardiomyocytes. CONCLUSIONS: H2S improves glucose utilization and inhibits cardiomyocyte hypertrophy

(22) Hine C, Mitchell JR. Calorie restriction and methionine restriction in control of endogenous hydrogen sulfide production by the transsulfuration pathway. Exp Gerontol 2014 Dec 16. Abstract: H2S is a gas easily identified by its distinctive odor. Although environmental exposure to H2S has been viewed alternately as therapeutic or toxic through the centuries, H2S has recently regained recognition for its numerous beneficial biological effects. Most experiments documenting such benefits, including improved glucose tolerance, increased stress resistance, and even lifespan extension, are based on exposure of experimental organisms to exogenous sources of H2S. However, appreciation is growing for the importance of H2S produced endogenously by the evolutionary conserved transsulfuration pathway (TSP) in health and longevity. Recent data implicate H2S produced by the TSP in pleiotropic benefits of dietary restriction (DR), or reduced nutrient/energy intake without malnutrition. DR, best known as the most reliable way to extend lifespan in a wide range of experimental organisms, includes various regimens aimed at either reducing overall calorie intake (calorie restriction, intermittent/every-other-day fasting) or reducing particular nutrients such as protein or the essential amino acid, methionine (methionine restriction), with overlapping functional benefits on stress resistance, metabolic fitness and lifespan. Here we will review the small but growing body of literature linking the TSP to the functional benefits of DR in part through the production of endogenous H2S, with an emphasis on regulation of the TSP and H2S production by diet and mechanisms of beneficial H2S action

(23) Kurada S, Alkhouri N, Fiocchi C, Dweik R, Rieder F. Review article: breath analysis in inflammatory bowel diseases. Aliment Pharmacol Ther 2014 Dec 19. Abstract: BACKGROUND: There is an urgent need for cheap, reproducible, easy to perform and specific biomarkers for diagnosis, differentiation and stratification of inflammatory bowel disease (IBD) patients. Technical advances allow for the determination of volatile organic compounds in the human breath to differentiate between health and disease. AIM: Review and discuss medical literature on volatile organic compounds in exhaled human breath in GI disorders, focusing on diagnosis and differentiation of IBD. METHODS: A systematic search in PubMed, Ovid Medline and Scopus was completed using appropriate keywords. In addition, a bibliography search of each article was performed. RESULTS: Mean breath pentane, ethane, propane, 1-octene, 3-methylhexane, 1-decene and NO levels were elevated (P < 0.05 to P < 10-7 ) and mean breath 1-nonene, (E)-2-nonene, hydrogen sulphide and methane were decreased in IBD compared to healthy controls (P = 0.003 to P < 0.001). A combined panel of 3 volatile organic compounds (octene, (E)-2-nonene and decene) showed the best discrimination between paediatric IBD and controls (AUC 0.96). Breath condensate cytokines were higher in IBD compared to healthy individuals (P < 0.008). Breath pentane, ethane, propane, isoprene and NO levels correlated with disease activity in IBD patients. Breath condensate interleukin-1beta showed an inverse relation with clinical disease activity. CONCLUSIONS: Breath analysis in IBD is a promising approach that is not yet ready for routine clinical use, but data from

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other gastrointestinal diseases suggest the feasibility for use of this technology in clinical practice. Well-designed future trials, incorporating the latest breath detection techniques, need to determine the exact breath metabolome pattern linked to diagnosis and phenotype of IBD

(24) Ruder JB, Ward JG, Taylor S, Giles K, Higgins T, Haan JM. Hydrogen Sulfide Suicide: A New Trend and Threat to Healthcare Providers. J Burn Care Res 2014 Dec 17. Abstract: First popularized in Japan, hydrogen sulfide (H2S) gas suicide is an underreported form of suicide with known risk for secondary disaster. Mortality rate commonly exceeds 90%because of the gas's lethal, noncontained nature. Instances in the United States are increasing, up from 2 cases in 2008 to 18 in 2010. Because H2S poisonings remain rare, there exists a lack of knowledge regarding the residual effects of gas venting after victim extrication. Identifying instances of the efficacious use of personal protection equipment (PPE) is critical in the effort to alleviate risks faced by hospital and rescue personnel. The current case demonstrates the effective use of PPEs after prolonged H2S exposure. In 2011, a 20-year-old man threatened suicide using H2S gas inside a vehicle on a remote rural highway. First responders identified a "rotten egg smell" and subsequently experienced low poisoning symptoms. After prolonged Hazmat-assisted extrication (4 hours) the patient was unconscious and experiencing seizures. He was decontaminated on-scene (20 minutes) and transported to the closest hospital (22 minutes). Ambulance personnel who wore PPE and used the ambulance's reverse ventilation system (RVS)reported no adverse effects. The patient was transferred to the authors' burn facility by helicopter (38 minutes). Life-flight personnel, who did not wear PPE (no ventilatory system available), complained of watery eyes, headache, and dizziness. Hospital personnel, who did not use PPE (or RVS), complained of watery eyes or headache. Exposed personnel demonstrated no deficits or residual effects. In spite of spontaneous movement, the patient began to seize and died. This case is unique given the multiple primary and secondary H2S gas exposures involved. Exposed personnel without RVS and not using PPE demonstrated moderate H2S symptoms. PPE (self-contained breathing apparatuses) and RVS were shown to be effective during an H2S emergency; however, there are currently limited data supporting their appropriate use. Until data demonstrating duration of H2S venting for small enclosed spaces are made available, PPEs should be required

(25) Beltowski J, Jamroz-Wisniewska A. Hydrogen Sulfide and Endothelium-Dependent Vasorelaxation. Molecules 2014;19(12):21183-99. Abstract: In addition to nitric oxide and carbon monoxide, hydrogen sulfide (H2S), synthesized enzymatically from l-cysteine or l-homocysteine, is the third gasotransmitter in mammals. Endogenous H2S is involved in the regulation of many physiological processes, including vascular tone. Although initially it was suggested that in the vascular wall H2S is synthesized only by smooth muscle cells and relaxes them by activating ATP-sensitive potassium channels, more recent studies indicate that H2S is synthesized in endothelial cells as well. Endothelial H2S production is stimulated by many factors, including acetylcholine, shear stress, adipose tissue hormone leptin, estrogens and plant flavonoids. In some vascular preparations H2S plays a role of endothelium-derived hyperpolarizing factor by activating small and intermediate-conductance calcium-activated potassium channels. Endothelial H2S signaling is up-regulated in some pathologies, such as obesity and cerebral ischemia-reperfusion. In addition, H2S activates endothelial NO synthase and inhibits cGMP degradation by phosphodiesterase 5 thus potentiating the effect of NO-cGMP pathway. Moreover, H2S-derived polysulfides directly activate protein kinase G. Finally, H2S interacts with NO to form nitroxyl (HNO)-a potent vasorelaxant. H2S appears to play an important and multidimensional role in endothelium-dependent vasorelaxation

(26) Winter G, Cordente AG, Curtin C. Formation of Hydrogen Sulfide from Cysteine in Saccharomyces cerevisiae BY4742: Genome Wide Screen Reveals a Central Role of the Vacuole. PLoS One 2014;9(12):e113869.

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Abstract: Discoveries on the toxic effects of cysteine accumulation and, particularly, recent findings on the many physiological roles of one of the products of cysteine catabolism, hydrogen sulfide (H2S), are highlighting the importance of this amino acid and sulfur metabolism in a range of cellular activities. It is also highlighting how little we know about this critical part of cellular metabolism. In the work described here, a genome-wide screen using a deletion collection of Saccharomyces cerevisiae revealed a surprising set of genes associated with this process. In addition, the yeast vacuole, not previously associated with cysteine catabolism, emerged as an important compartment for cysteine degradation. Most prominent among the vacuole-related mutants were those involved in vacuole acidification; we identified each of the eight subunits of a vacuole acidification sub-complex (V1 of the yeast V-ATPase) as essential for cysteine degradation. Other functions identified included translation, RNA processing, folate-derived one-carbon metabolism, and mitochondrial iron-sulfur homeostasis. This work identified for the first time cellular factors affecting the fundamental process of cysteine catabolism. Results obtained significantly contribute to the understanding of this process and may provide insight into the underlying cause of cysteine accumulation and H2S generation in eukaryotes

(27) Desloover J, De VJ, Van d, V, Mortelmans J, Rozendal R, Rabaey K. Electrochemical Nutrient Recovery Enables Ammonia Toxicity Control and Biogas Desulfurization in Anaerobic Digestion. Environ Sci Technol 2015 Jan 6. Abstract: Organic waste streams can be valorized and reduced in volume with anaerobic digestion (AD). An often-encountered key issue however is the high ammonium (NH4+) content of certain waste streams. Ammonia (NH3), in equilibrium with NH4+, is a toxic compound to the methanogenic community, which limits the organic loading rate and endangers process stability. An electrochemical system (ES) linked to a digester could, besides recovering this nutrient, decrease NH3 toxicity through electrochemical extraction. Therefore, two digesters with and without ES attached in the recirculation loop were operated to test whether the ES could control NH3 toxicity. During periods of high ammonium loading rates, the methane (CH4) production of the ES-coupled reactor was up to 4.5 times higher compared to the control, which could be explained through simultaneous NH4+ extraction and electrochemical pH control. A nitrogen flux of 47 g N m-2 membrane d-1 could be obtained in the ES-coupled reactor, resulting in a current and removal efficiency of 38 +/- 5% and 28 +/- 2%, respectively, at an electrochemical power input of 17 +/- 2 kWh kg-1 N. The anode also oxidized sulfide, resulting in a significantly lower H2S emission via the biogas. Lastly, limited methanogenic community dynamics pointed to a nonselective influence of the different operational conditions

(28) Zhou X, Zhao L, Mao J, Huang J, Chen J. Antioxidant effects of hydrogen sulfide on left ventricular remodeling in smoking rats are mediated via PI3K/Akt-dependent activation of Nrf2. Toxicol Sci 2014 Dec 16. Abstract: There is growing evidence that oxidative stress plays critical roles in the pathogenesis of cardiac remodeling. In the present study, we established a rat model of passive smoking and investigated the antioxidant effects of hydrogen sulfide (H2S) on smoking-induced left ventricular remodeling. Cardiac structure and function were evaluated using two-dimensional echocardiography. Myocardial fibrosis was detected by Masson's trichrome staining and immunohistochemistry. Oxidative stress was assessed by measuring malondialdehyde levels, superoxide dismutase and glutathione peroxidase activities, and reactive oxygen species generation in the myocardium. Neonatal rat cardiomyocytes transfected with specific siRNA and exposed to cigarette smoke condensate and H2S donor sodium hydrosulfide were used to confirm the involvement of Nrf2 and PI3K/Akt signaling in the antioxidant effects of H2S. Our results indicated that H2S could protect against left ventricular remodeling in smoking rats via attenuation of oxidative stress. Moreover, H2S was also found to increase the phosphorylation of Akt and GSK3beta and decrease the nuclear expression of Fyn, which consequently leads to nuclear translocation of Nrf2 and elevated expression of HO-1 and NQO1. In conclusion,

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H2S may exert antioxidant effects on left ventricular remodeling in smoking rats via PI3K/Akt-dependent activation of Nrf2 signaling

(29) Collins N, Brewer M. Development of a Clinically Applicable Protocol for Assessment of Hypoxic Response Through Measurement of the Endogenous Gasotransmitter Hydrogen Sulfide in Human Plasma. J Neurosurg Anesthesiol 2014 Dec 15. Abstract: BACKGROUND:: Gasotransmitters are endogenously made, biologically active gases with unique physiological properties. In addition to participation in the hypoxic respiratory reflex of the carotid body, the gasotransmitter hydrogen sulfide (H2S) is thought to play a role in more localized vasodilatory hypoxic tissue responses. This pilot project describes a methodology suitable to the clinical environment that allows for H2S gas capture in human plasma utilizing the fluorescent trapping agent dansyl azide. METHODS:: Under an IRB-approved pilot project, 10 healthy male volunteers were spontaneously ventilated on room air, hypoxic (15% oxygen, 85% nitrogen), and hyperoxic (100%) gas mixtures through a nonrebreather system. Venous whole-blood samples were collected at both internal jugular and antecubital sites following 7 minutes of exposure to the tested oxygen environments. Resultant plasma aliquots were treated with dansyl azide and submitted to fluorescence reading (excitation 340 nm, emission 517 nm). RESULTS:: Compiled mean data from volunteer plasma samples demonstrated statistically significant findings (P<0.05) in measurement of increased fluorescent intensity between those samples collected under mildly hypoxic conditions compared with normoxic and hyperoxic samples submitted to the same laboratory criteria. CONCLUSIONS:: To study the role of H2S as a marker of hypoxic response in humans, a reliable, robust, and safe protocol amenable to standard hospital laboratory procedures is needed. Through modification to methodologies described in the biochemistry literature, this pilot project demonstrates the feasibility of utilizing a fluorescent H2S gas trapping agent for assessment of hypoxic response in humans within the confines of a typical clinical collection and analysis environment

(30) Pan LL, Wang XL, Wang XL, Zhu YZ. Sodium Hydrosulfide Prevents Myocardial Dysfunction through Modulation of Extracellular Matrix Accumulation and Vascular Density. Int J Mol Sci 2014;15(12):23212-26. Abstract: The aim was to examine the role of exogenous hydrogen sulfide (H2S) on cardiac remodeling in post-myocardial infarction (MI) rats. MI was induced in rats by ligation of coronary artery. After treatment with sodium hydrosulfide (NaHS, an exogenous H2S donor, 56 muM/kg.day) for 42 days, the effects of NaHS on left ventricular morphometric features, echocardiographic parameters, heme oxygenase-1 (HO-1), matrix metalloproteinases-9 (MMP-9), type I and type III collagen, vascular endothelial growth factor (VEGF), CD34, and alpha-smooth muscle actin (alpha-SMA) in the border zone of infarct area were analyzed to elucidate the protective mechanisms of exogenous H2S on cardiac function and fibrosis. Forty-two days post MI, NaHS-treatment resulted in a decrease in myocardial fibrotic area in association with decreased levels of type I, type III collagen and MMP-9 and improved cardiac function. Meanwhile, NaHS administration significantly increased cystathionine gamma-lyase (CSE), HO-1, alpha-SMA, and VEGF expression. This effect was accompanied by an increase in vascular density in the border zone of infarcted myocardium. Our results provided the strong evidences that exogenous H2S prevented cardiac remodeling, at least in part, through inhibition of extracellular matrix accumulation and increase in vascular density

(31) Hatzoglou M, Snider MD, Maruvada P. It's all about balance: cellular responses to nutrients and development of disease. Adv Nutr 2014 Sep;5(5):558-60. Abstract: Responding to nutrient availability is an important homeostatic mechanism in the growth, development, and function of cells and tissues. However, these adaptations can also play a role in the development of disease. Our symposium, "Cellular Responses to Nutrients and Development of Disease," presented research about how cells sense nutrients and how the resulting signal transduction controls cellular processes from gene

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transcription to impacting various pathophysiologic processes. Dr. Michael Kilberg discussed the transcription program triggered by amino acid limitation that leads to growth arrest in normal cells and sustained growth in tumor cells. Dr. Noa Noy elaborated on the role of lipid-binding proteins in retinoic acid signaling, focusing on fatty acid-binding protein 5 (FABP5), which promotes cell growth by delivering this molecule to the nuclear receptor peroxisome proliferator-activated receptor delta (PPARdelta). Dr. Li-Na Wei discussed the many functions of the protein receptor interacting protein 140 (RIP140) as a coregulator of nuclear receptors and as a cytoplasmic protein that regulates insulin-stimulated glucose uptake, lipolysis, and inflammation. Dr. Ruma Banerjee presented state-of-the-art approaches for studying the gaseous signaling molecule hydrogen sulfide (H2S), discussing its concentrations, metabolism, and functions in the regulation of redox signaling. Finally, Dr. Maria Hatzoglou described how the stress-induced increases in amino acid transport, mammalian target of rapamycin (mTOR) signaling, and protein synthesis in pancreatic beta-cells can contribute to the progression of diabetes

(32) Vasas A, Doka E, Fabian I, Nagy P. Kinetic and thermodynamic studies on the disulfide-bond reducing potential of hydrogen sulfide. Nitric Oxide 2014 Dec 12. Abstract: The significance of persulfide species in hydrogen sulfide biology is increasingly recognized. However, the molecular mechanisms of their formation remain largely elusive. The obvious pathway of the reduction of biologically abundant disulfide moieties by sulfide was challenged on both thermodynamic and kinetic grounds. Using DTNB (5,5'-dithiobis-(2-nitrobenzoic acid), also known as Ellman's reagent) as a model disulfide we conducted a comprehensive kinetic study for its reaction with sulfide. The bimolecular reaction is relatively fast with a second-order rate constant of 889 +/- 12 M-1s-1 at pH = 7.4. pH dependence of the rate law revealed that the reaction proceeds via the bisulfide anion species with an initial nucleophilic thiol-disulfide exchange reaction to give 5-thio-2-nitrobenzoic acid (TNB) and TNB-persulfide with a pH independent second-order rate constant of 1090 +/- 12 M-1s-1. However, kinetic studies and stoichiometric analyses in a wide range of reactant ratios together with kinetic simulations revealed that it is a multistep process that proceeds via kinetically driven, practically irreversible reactions along the disulfide --> persulfide --> inorganic polysulfides axis. The kinetic model postulated here, which is fully consistent with the experimental data, suggests that the TNB-persulfide is further reduced by sulfide with a second-order rate constant in the range of 5 x

(33) Fawcett EM, Hoyt JM, Johnson JK, Miller DL. Hypoxia disrupts proteostasis in Caenorhabditis elegans. Aging Cell 2014 Dec 16. Abstract: Oxygen is fundamentally important for cell metabolism, and as a consequence, O2 deprivation (hypoxia) can impair many essential physiological processes. Here, we show that an active response to hypoxia disrupts cellular proteostasis - the coordination of protein synthesis, quality control, and degradation that maintains the functionality of the proteome. We have discovered that specific hypoxic conditions enhance the aggregation and toxicity of aggregation-prone proteins that are associated with neurodegenerative diseases. Our data indicate this is an active response to hypoxia, rather than a passive consequence of energy limitation. This response to hypoxia is partially antagonized by the conserved hypoxia-inducible transcription factor, hif-1. We further demonstrate that exposure to hydrogen sulfide (H2 S) protects animals from hypoxia-induced disruption of proteostasis. H2 S has been shown to protect against hypoxic damage in mammals and extends lifespan in nematodes. Remarkably, our data also show that H2 S can reverse detrimental effects of hypoxia on proteostasis. Our data indicate that the protective effects of H2 S in hypoxia are mechanistically distinct from the effect of H2 S to increase lifespan and thermotolerance, suggesting that control of proteostasis and aging can be dissociated. Together, our studies reveal a novel effect of the hypoxia response in animals and provide a foundation to understand how the integrated proteostasis network is integrated with this stress response pathway

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(34) Sadeghi HR, Toosi MH, Soudmand S, Sadoughi HR, Sazgarnia A. Gold-Gold Sulfide nanoparticles intensify thermal effects of radio frequency electromagnetic field. J Exp Ther Oncol 2014;10(4):285-91. Abstract: PURPOSE: This study aimed to determine the efficacy of thermotherapy resulting from the presence of gold-gold sulfide nanoshells (GGS) in radio frequency electromagnetic field (13.56 MHz) onthe survival of CT26 colon carcinoma cells. MATERIALS AND METHODS: GGS was synthesized and after characterizing and determining the features, the RF-radiation effects on aquatic environments were determined by recording temperature changes. To investigate the biological effects, cell survival rate due to GGS usage at five different concentrations, each one with applying three different exposure times of RF field, at CT26 cells were evaluated by MTT assay. RESULT: In the presence of 100 mg/L GGS and 5 min RF exposure, increasing in temperature was recorded more than 60 degrees C. A significant difference in cell survival rate was observed, when both GGS and RF field were applied with each other or separately (p<0.001). The GGS concentration of 25mg/L with a 4 min exposure causes cell death with the efficiency of 80 percent more than using them separately. CONCLUSION: The GGS as an available nanostructure (i.e. it's not expensive and can be synthesized simply) is an environmental friendly material which has the ability to cause damage to malignant cell effectively, by absorbing the non-invasive and deeply penetrating energy of RF field

(35) Liu HY, Shi RJ, Zhang Y, Shi ZG, Zhang YY, Yu L, et al. [NO3-/NO2- inhibits sulfate-reducing activity of the enrichment culture of sulfate-reducing prokaryotes from an off-shore oil reservoir at Bohai Bay, China]. Ying Yong Sheng Tai Xue Bao 2014 Aug;25(8):2369-76. Abstract: Long-term injection of sulfate-rich water into oil reservoirs stimulates the proliferation of sulfate-reducing prokaryotes (SRP) therein and results in production of a great amount of H2S, leading to souring in oil reservoirs and related environmental problems. In this study, we first, using modified API RP 38 medium, enriched SRP present in production water from a producing well at Bohai Bay, China, and then examined the inhibitory effects of nitrate or nitrite on sulfate reduction activity of the SRP. Results showed that the enriched SRP culture exhibited a high sulfate reduction activity as indicated by a sulfate-reducing rate of 10.4 mmol SO4(2-) x d(-1) x g(-1) dry cell. In presence of 0.4, 0.8, 1.8, and 4.2 mmol x L(-1) nitrate, sulfate reduction was inhibited for 5, 9, 20, and over 35 days, respectively. With the addition of 0.6, 0.9, 1.4, 2.6 and 4.6 mmol x L(-1) of nitrite, the inhibitory period lasted 3, 12, 22, and over 39 days, respectively. The SRP enrichment culture could dissimilatorily reduce nitrate to ammonium. When sulfate, nitrate and nitrite coexisted, nitrate or nitrite was preferentially used over sulfate as electron acceptor by the enriched SRP. This competitive use of electron acceptor and the strong inhibitory effect of nitrite possibly accounted for the suppression of nitrate and nitrite on the sulfate-reducing activity of the enriched SRP cultures from offshore oil reservoir at Bohai Bay

(36) Lin JQ, Luo HQ, Lin CZ, Chen JZ, Lin XZ. Sodium hydrosulfide relieves neuropathic pain in chronic constriction injured rats. Evid Based Complement Alternat Med 2014;2014:514898. Abstract: Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain (NPP). Channel protein pCREB of that activity has been shown to mitigate the onset of associated molecular events in the nervous system, and sodium hydrosulfide (NaHS) could inhibit the expression of pCREB. However, whether NaHS could relieve the pain, it needs further experimental research. Furthermore, the clinical potential that NaHS was used to relieve pain was limited so it would be required. To address these issues, the rats of sciatic nerve chronic constriction injury (CCI) were given intraperitoneal injection of NaHS containing hydrogen sulfide (H2S). The experimental results showed that NaHS inhibited the reduction of paw withdrawal thermal latency (PWTL), mechanical withdrawal threshold (MWT), and the level of pCREB in CCI rats in a dose-dependent manner and they were greatly decreased in NaHSM group

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(P < 0.05). NaHS alleviates chronic neuropathic pain by inhibiting expression of pCREB in the spinal cord of Sprague-Dawley rats

(37) He L, Lin W, Xu Q, Wei H. A new strategy to construct a FRET platform for ratiometric sensing of hydrogen sulfide. Chem Commun (Camb ) 2015 Jan 2;51(8):1510-3. Abstract: We introduce a new FRET strategy to construct a ratiometric fluorescent H2S sensor. The ratio emission signal of the coumarin-naphthalimide dyad is modulated by the FRET process, which works in coordination with the ICT mechanism. The FRET process on/off is controlled through tuning the overlap level of the donor emission spectrum with the acceptor absorption via modulation of the acceptor fluorophore absorption wavelength. was applied to visualize both the intracellular exogenous and endogenous H2S through blue and green emission channels

(38) Bamesberger A, Kim G, Woo J, Cao H. Reduction of Nitro Group on Derivative of 1,8-Napthalimide for Quantitative Detection of Hydrogen Sulfide. J Fluoresc 2014 Dec 11. Abstract: A fluorescence "turn-on" sensor (HSS) for detection of H2S was developed on the basis of NO2-NH2 reduction. HSS showed a high affinity and sensitivity to H2S over other reducing reagents, particularly for biothiols. Also, the short responding time and high linear dependence between fluorescence enhancement and H2S concentration had HSS behave as a rapid sensor for quantitatively detection of H2S in the biological level

(39) Nagasaki T, Hongo Y, Koito T, Nakamura-Kusakabe I, Shimamura S, Takaki Y, et al. Cysteine dioxygenase and cysteine sulfinate decarboxylase genes of the deep-sea mussel Bathymodiolus septemdierum: possible involvement in hypotaurine synthesis and adaptation to hydrogen sulfide. Amino Acids 2014 Dec 16. Abstract: It has been suggested that invertebrates inhabiting deep-sea hydrothermal vent areas use the sulfinic acid hypotaurine, a precursor of taurine, to protect against the toxicity of hydrogen sulfide contained in the seawater from the vent. In this protective system, hypotaurine is accumulated in the gill, the primary site of sulfide exposure. However, the pathway for hypotaurine synthesis in mollusks has not been identified. In this study, we screened for the mRNAs of enzymes involved in hypotaurine synthesis in the deep-sea mussel Bathymodiolus septemdierum and cloned cDNAs encoding cysteine dioxygenase and cysteine sulfinate decarboxylase. As mRNAs encoding cysteamine dioxygenase and cysteine lyase were not detected, the cysteine sulfinate pathway is suggested to be the major pathway of hypotaurine and taurine synthesis. The two genes were found to be expressed in all the tissues examined, but the gill exhibited the highest expression. The mRNA level in the gill was not significantly changed by exposure to sulfides or thiosulfate. These results suggests that the gill of B. septemdierum maintains high levels of expression of the two genes regardless of ambient sulfide level and accumulates hypotaurine continuously to protect against sudden exposure to high level of sulfide

(40) Sun W, Barlaz MA. Measurement of chemical leaching potential of sulfate from landfill disposed sulfate containing wastes. Waste Manag 2014 Dec 11. Abstract: A number of sulfate-containing wastes are disposed in municipal solid wastes (MSW) landfills including residues from coal, wood, and MSW combustion, and construction and demolition (C&D) waste. Under anaerobic conditions that dominate landfills, the sulfate can be reduced to hydrogen sulfide which is problematic for several reasons including its low odor threshold, toxicity, and corrosive nature. The overall objective of this study was to evaluate existing protocols for the quantification of total leachable sulfate from solid samples and to compare their effectiveness and efficiency with a new protocol described in this study. Methods compared include two existing acid extraction protocols commonly used in the U.S., a pH neutral protocol that requires multiple changes of the leaching solution, and a new acid extraction method. The new acid extraction method was shown to be simple and effective to measure the leaching potential of sulfate from a range of landfill disposed sulfate-containing wastes. However, the acid

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extraction methods do not distinguish between sulfate and other forms of sulfur and are thus most useful when sulfate is the only form of sulfur present

(41) Fukushima N, Ieda N, Kawaguchi M, Sasakura K, Nagano T, Hanaoka K, et al. Development of photo-controllable hydrogen sulfide donor applicable in live cells. Bioorg Med Chem Lett 2015 Jan 15;25(2):175-8. Abstract: Hydrogen sulfide (H2S) has multiple physiological roles, for example, in vasodilation and inflammation. It is a highly reactive gas under ambient conditions, so controllable H2S donors are required for studying its biological functions. Here, we describe the design, synthesis and application of a H2S donor (SPD-2) that utilizes xanthone photochemistry to control H2S release. H2S generation from SPD-2 was completely dependent on UVA-irradiation (325-385nm), as confirmed by methylene blue assay and by the use of a H2S-selective fluorescent probe. SPD-2 was confirmed to provide controlled H2S delivery in live cells, and should be suitable for various biological applications

(42) Singha S, Kim D, Moon H, Wang T, Kim KH, Shin YH, et al. Toward a Selective, Sensitive, Fast-Responsive, and Biocompatible Two-Photon Probe for Hydrogen Sulfide in Live Cells. Anal Chem 2014 Dec 24. Abstract: Hydrogen sulfide has emerged as an exciting endogenous gasotransmitter in addition to nitric oxide and carbon dioxide. Noninvasive detection methods for hydrogen sulfide thus become indispensable tools for studying its diverse roles in biological systems. Accordingly, fluorescent probes for hydrogen sulfide have received great attention in recent years. A practically useful fluorescent probe for bioimaging of hydrogen sulfide should be selective, sensitive, fast-responsive, biocompatible, observable in the biological optical window, and capable of deep-tissue imaging. These sensing properties, however, are extremely difficult to achieve at the same time. Disclosed here is the two-photon fluorescent probe that meets all of these criteria. The probe belongs to a Michael acceptor system, which raised a serious selectivity issue over the competing biothiols such as cysteine and glutathione. We have addressed the selectivity issue by optimizing the electronic and steric interactions between biothiols and the probe, in addition to achieving very high sensitivity, fast-response, and biocompatibility. Also, the sensing mechanism suggested in the literature was revised. The probe thus enables us to image the endogenously produced hydrogen sulfide with negligible interference from other biothiols in live cells. The excellent sensing properties of the probe combined with its capability of bioimaging thus make it a practically useful tool for further studying biological roles of hydrogen sulfide

(43) Sarna LK, Siow YL, O K. The CBS/CSE system: a potential therapeutic target in NAFLD? Can J Physiol Pharmacol 2015 Jan;93(1):1-11. Abstract: Non-alcoholic fatty liver disease (NAFLD) is a broad spectrum liver disorder diagnosed in patients without a history of alcohol abuse. NAFLD is growing at alarming rates worldwide. Its pathogenesis is complex and incompletely understood. The cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) system regulates homocysteine and cysteine metabolism and contributes to endogenous hydrogen sulfide (H2S) biosynthesis. This review summarizes our current understanding of the hepatic CBS/CSE system, and for the first time, positions this system as a potential therapeutic target in NAFLD. As will be discussed, the CBS/CSE system is highly expressed and active in the liver. Its dysregulation, presenting as alterations in circulating homocysteine and (or) H2S levels, has been reported in NAFLD patients and in NAFLD-associated co-morbidities such as obesity and type 2 diabetes. Intricate links between the CBS/CSE system and a number of metabolic and stress related molecular mediators have also emerged. Various dysfunctions in the hepatic CBS/CSE system have been reported in animal models representative of each NAFLD spectrum. It is anticipated that a newfound appreciation for the hepatic CBS/CSE system will emerge that will improve our understanding of NAFLD pathogenesis, and give rise to new prospective targets for management of this disorder

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(44) Geng Y, Li E, Mu Q, Zhang Y, Wei X, Li H, et al. Hydrogen sulfide inhalation decreases early blood-brain barrier permeability and brain edema induced by cardiac arrest and resuscitation. J Cereb Blood Flow Metab 2014 Dec 10. Abstract: The effects of hydrogen sulfide (H2S) on blood-brain barrier (BBB) and brain edema after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) remain poorly understood. We investigated the effects of exogenous 80-p.p.m. H2S gas on BBB, brain water content, neurologic outcome, and survival rate after CA and CPR. Cardiopulmonary resuscitation followed CA induced in rats by ventricular fibrillation for 6 minutes. Results show that inhalation of 80-p.p.m. H2S significantly reduced the permeability of the BBB in both in the cortex and hippocampus at 24 hours after resuscitation. Hydrogen sulfide also lessened brain edema in the cortex and hippocampus, ameliorated neurologic outcome as evaluated by neurologic deficit score and tape removal test, and improved the 14-day survival rate. Hydrogen sulfide also attenuated CA and CPR-induced increases of matrix metalloproteinase-9 (MMP-9) activity and vascular endothelial growth factor (VEGF) expression, and increased the expression of angiogenin-1 (Ang-1). These results indicate that inhalation of 80-p.p.m. H2S immediately after CPR attenuated BBB permeability and brain edema, and improved neurologic outcome and 14-day survival of rats after CA. The therapeutic benefits of H2S could be associated with suppression of MMP-9 and VEGF expression and increased expression of Ang-1.Journal of Cerebral Blood Flow & Metabolism advance online publication, 10 December 2014; doi:10.1038/jcbfm.2014.223

(45) Fasolino I, Izzo AA, Clavel T, Romano B, Haller D, Borrelli F. Orally-administered allyl sulfides from garlic ameliorate murine colitis. Mol Nutr Food Res 2014 Dec 9. Abstract: SCOPE:: Inflammatory bowel disease (IBD) is an incurable disease which affects millions of people. Garlic (Allium sativum) preparations have been traditionally employed for the treatment of diseases affecting the digestive tract. Here, we have investigated the effect of diallyl sulfide (DAS) and diallyl disulfide (DADS), two garlic-derived sulfur compounds, on intestinal inflammation in vivo as well as in intestinal isolated cells. METHODS AND RESULTS:: Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid. Intestinal damage was assessed by evaluating colon weight/colon length ratio and by histology. Murine intestinal epithelial cells stimulated with interferon-gamma (IFN-gamma) were used to evaluate the possible in vitro DAS and DADS anti-inflammatory effects. DAS and DADS, given for two consecutive days after DNBS administration, reduced inflammation and damage. In IFN-gamma-stimulated intestinal epithelial cells, DADS reduced IP-10 and IL-6 levels, while DAS inhibited nitric oxide production and STAT-1 expression CONCLUSION: : DAS and DADS exert therapeutic effects in the DNBS model of colitis. The actions of these compounds on the production of IP-10, IL-6, hydrogen sulfide or nitric oxide and on the expression of STAT-1 observed in intestinal cells stimulated with IFN-gamma, might explain the protective action of DAS and DADS in experimental IBD. This article is protected by copyright. All rights reserved

(46) Paul BD, Snyder SH. Neurodegeneration in Huntington's disease involves loss of cystathionine gamma-lyase. Cell Cycle 2014 Aug 15;13(16):2491-3.

(47) Fu Y, Zhao Y, Wang P, Xing L, Xue X. High response and selectivity of a Cu-ZnO nanowire nanogenerator as a self-powered/active H2S sensor. Phys Chem Chem Phys 2015 Jan 21;17(3):2121-6. Abstract: Room-temperature self-powered H2S sensing with high response and selectivity has been realized from a Cu-ZnO nanowire nanogenerator. Upon exposure to 1000 ppm H2S at room temperature, the piezoelectric output voltage of the device (5 at% Cu-ZnO) under compressive force decreases from 0.552 (in dry air) to 0.049 V, and the response is up to 1045, over 8 times larger than that of undoped ZnO nanowires. The selectivity against H2S is also very high at room temperature. The enhanced room-temperature H2S sensing performance can be attributed to the coupling of the piezoelectric screening effect of ZnO nanowires and the synergistic effect of the Cu dopant. This study should stimulate research into designing a new gas sensor for detecting toxic gases at room temperature

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(48) Yamamoto T, Kim KH, Shirono K. A pilot study on remediation of sediments enriched by oyster farming wastes using granulated coal ash. Mar Pollut Bull 2015 Jan 15;90(1-2):54-9. Abstract: In order to evaluate the ability of granulated coal ash (GCA), a byproduct of coal thermal electric power stations, to remove hydrogen sulfide from organically enriched sediments, a pilot study was carried out at oyster farming sites, where sediments were enriched with oyster feces and dead oysters. Concentration of hydrogen sulfide in the interstitial water of the sediment decreased to nearly zero in both experimental sites, whereas it remained over 0.2mg/l in the control site. Concentration of acid volatile sulfide (AVS) in the sediment also decreased significantly in both experimental sites, while remained over 0.4mg/g in the control site. Increases were observed in both the number of benthic microalgae species and the individual number of benthic animals in the surface sediments. This may have been due to the decrease in hydrogen sulfide

(49) Lachet V, Teuler JM, Rousseau B. Classical Force Field for Hydrofluorocarbon Molecular Simulations. Application to the Study of Gas Solubility in Poly(vinylidene fluoride). J Phys Chem A 2015 Jan 8;119(1):140-51. Abstract: A classical all-atoms force field for molecular simulations of hydrofluorocarbons (HFCs) has been developed. Lennard-Jones force centers plus point charges are used to represent dispersion-repulsion and electrostatic interactions. Parametrization of this force field has been performed iteratively using three target properties of pentafluorobutane: the quantum energy of an isolated molecule, the dielectric constant in the liquid phase, and the compressed liquid density. The accuracy and transferability of this new force field has been demonstrated through the simulation of different thermophysical properties of several fluorinated compounds, showing significant improvements compared to existing models. This new force field has been applied to study solubilities of several gases in poly(vinylidene fluoride) (PVDF) above the melting temperature of this polymer. The solubility of CH4, CO2, H2S, H2, N2, O2, and H2O at infinite dilution has been computed using test particle insertions in the course of a NpT hybrid Monte Carlo simulation. For CH4, CO2, and their mixtures, some calculations beyond the Henry regime have also been performed using hybrid Monte Carlo simulations in the osmotic ensemble, allowing both swelling and solubility determination. An ideal mixing behavior is observed, with identical solubility coefficients in the mixtures and in pure gas systems

(50) Qian Y, Lin J, Liu T, Zhu H. Living cells imaging for copper and hydrogen sulfide by a selective "on-off-on" fluorescent probe. Talanta 2015 Jan 15;132:727-32. Abstract: A novel highly selective and sensitive fluorescent probe (NJ1) had been designed and synthesized for Cu(2+) detection by fluorescence quenching mechanism, and then the enhancement of fluorescence intensity with the addition of hydrogen sulfide in complex NJ1Cu aqueous solution at physiological conditions were described. This "on-off-on" type fluorescence recognition system was a reversible process, which could be utilized to monitor copper ion and hydrogen sulfide based on a complex NJ1Cu formation-Cu(2+) displacement approach. Importantly, this real-time recognition process of Cu(2+) and hydrogen sulfide exhibited excellent anti-interference ability. In addition, this new fluorescent probe also has potential utility for Cu(2+) and hydrogen sulfide detection in living cells, providing a potential tool for investigating copper ion and hydrogen sulfide in living systems or environment

(51) Ginson J, Panda SK, Bindu J, Kamalakanth CK, Srinivasa Gopal TK. Effect of high pressure treatment on microbiological quality of Indian white prawn (Fenneropenaeus indicus) during chilled storage. Food Microbiol 2015 Apr;46:596-603. Abstract: High pressure treatment of 250 MPa for 6 min at 25 degrees C was applied to headless Indian white prawn (Fenneropenaeus indicus) to evaluate changes in microbiological characteristics of the species during chilled storage. Changes in load of mesophilic bacteria, psychrotrophic bacteria, proteolytic bacteria, Enterobacteriaceae, Pseudomonas spp., H2S producing bacteria, lactic acid bacteria, Brochothrix thermosphacta and yeast & mold were estimated in pressurized and un-pressurized

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samples during chilled storage. All microbes were reduced significantly after high pressure treatment and there was significant difference in microbial quality of control and high pressure treated samples in the entire duration of chilled storage (p < 0.05). There was delay in the growth of Enterobacteriaceae and H2S producing bacteria up to 6th and 9th day of storage, respectively in high pressure treated samples. In high pressure treated sample, no lag phase (lambda) was observed for psychrotrophic bacteria, H2S producing bacteria, B. thermosphacta, Pseudomonas spp. and lactic acid bacteria; however, other bacteria showed a reduced lag phase during chilled storage. Kinetic parameter such as specific growth rate (mumax) in high pressure treated samples was significantly reduced in most of the bacterial groups except for psychrotrophic bacteria, Enterobacteriaceae and lactic acid bacteria. Mesophilic bacterial count of control samples crossed the marginal limit of acceptability on 12th day and unacceptable limit on 18th day of storage, whereas high pressure treated samples never breached the acceptability limit during entire duration of chilled storage. The present study indicated that application of high pressure processing can be used to improve microbial quality of Indian white prawn and extend the chilled storage life

(52) Lin VS, Chen W, Xian M, Chang CJ. Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems. Chem Soc Rev 2014 Dec 4. Abstract: Hydrogen sulfide (H2S), a gaseous species produced by both bacteria and higher eukaryotic organisms, including mammalian vertebrates, has attracted attention in recent years for its contributions to human health and disease. H2S has been proposed as a cytoprotectant and gasotransmitter in many tissue types, including mediating vascular tone in blood vessels as well as neuromodulation in the brain. The molecular mechanisms dictating how H2S affects cellular signaling and other physiological events remain insufficiently understood. Furthermore, the involvement of H2S in metal-binding interactions and formation of related RSS such as sulfane sulfur may contribute to other distinct signaling pathways. Owing to its widespread biological roles and unique chemical properties, H2S is an appealing target for chemical biology approaches to elucidate its production, trafficking, and downstream function. In this context, reaction-based fluorescent probes offer a versatile set of screening tools to visualize H2S pools in living systems. Three main strategies used in molecular probe development for H2S detection include azide and nitro group reduction, nucleophilic attack, and CuS precipitation. Each of these approaches exploits the strong nucleophilicity and reducing potency of H2S to achieve selectivity over other biothiols. In addition, a variety of methods have been developed for the detection of other reactive sulfur species (RSS), including sulfite and bisulfite, as well as sulfane sulfur species and related modifications such as S-nitrosothiols. Access to this growing chemical toolbox of new molecular probes for H2S and related RSS sets the stage for applying these developing technologies to probe reactive sulfur biology in living systems

(53) Campolo M, Esposito E, Ahmad A, Di PR, Paterniti I, Cordaro M, et al. Hydrogen sulfide-releasing cyclooxygenase inhibitor ATB-346 enhances motor function and reduces cortical lesion volume following traumatic brain injury in mice. J Neuroinflammation 2014 Dec 4;11(1):196. Abstract: BackgroundTraumatic brain injury (TBI) induces secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. We recently reported that administration of ATB-346 (2-(6-methoxynapthalen- 2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester), a hydrogen sulfide-releasing cyclooxygenase inhibitor, showed marked beneficial effects in an animal model of spinal cord injury, significantly enhancing recovery of motor function and reducing the secondary inflammation and tissue injury.MethodsHere we evaluated the neuroprotective potential of ATB-346, a hydrogen sulfide-releasing derivative of naproxen, using the controlled cortical impact (CCI) injury model in mice, one of the most common models of TBI. Moreover, the aim of the present study was to carefully investigate molecular pathways and subtypes of glial cells involved in the protective effect of ATB-346 on inflammatory reaction associated with an experimental

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model of TBI. In these studies, TBI was induced in mice by CCI and mice were orally administered ATB-346, naproxen (both at 30 inverted question markmol/kg) or vehicle (dimethylsulfoxide:1% carboxymethylcellulose [5:95] suspension) one and six hours after brain trauma and once daily for 10 days.ResultsResults revealed that ATB-346 attenuated TBI-induced brain edema, suppressed TBI-induced neural cell death and improved neurological function. ATB-346 also significantly reduced the severity of inflammation and restored neurotrophic factors that characterized the secondary events of TBI.ConclusionsThese data demonstrate that ATB-346 can be efficacious in a TBI animal model by reducing the secondary inflammation and tissue injury. Therefore, ATB-346 could represent an interesting approach for the management of secondary damage following CNS diseases, counteracting behavioral changes and inflammatory process

(54) Zhou Y, Chen W, Zhu J, Pei W, Wang C, Huang L, et al. Nanoprobes: Inorganic-Organic Hybrid Nanoprobe for NIR-Excited Imaging of Hydrogen Sulfide in Cell Cultures and Inflammation in a Mouse Model (Small 23/2014). Small 2014 Dec;10(23):4802. Abstract: Hydrogen sulfide (H2 S) is an important gaseous signaling agent mediated by many physiological processes. However, current downconversion H2 S probes are impractical for bioimaging due to the short tissue penetration of UV/visible light. As reported by J. S. C. Loo, Q. Zhang, and co-workers on page 4874, a new design for the NIR-excited imaging of H2 S is developed by using coumarin-hemicyanine (CHC1)-modified upconversion nanophosphors. This work can be further developed as a diagnostic tool for the detection of H2 S-induced inflammatory diseases

(55) Hatzoglou M, Snider MD, Maruvada P. It's all about balance: cellular responses to nutrients and development of disease. Adv Nutr 2014 Sep;5(5):558-60. Abstract: Responding to nutrient availability is an important homeostatic mechanism in the growth, development, and function of cells and tissues. However, these adaptations can also play a role in the development of disease. Our symposium, "Cellular Responses to Nutrients and Development of Disease," presented research about how cells sense nutrients and how the resulting signal transduction controls cellular processes from gene transcription to impacting various pathophysiologic processes. Dr. Michael Kilberg discussed the transcription program triggered by amino acid limitation that leads to growth arrest in normal cells and sustained growth in tumor cells. Dr. Noa Noy elaborated on the role of lipid-binding proteins in retinoic acid signaling, focusing on fatty acid-binding protein 5 (FABP5), which promotes cell growth by delivering this molecule to the nuclear receptor peroxisome proliferator-activated receptor delta (PPARdelta). Dr. Li-Na Wei discussed the many functions of the protein receptor interacting protein 140 (RIP140) as a coregulator of nuclear receptors and as a cytoplasmic protein that regulates insulin-stimulated glucose uptake, lipolysis, and inflammation. Dr. Ruma Banerjee presented state-of-the-art approaches for studying the gaseous signaling molecule hydrogen sulfide (H2S), discussing its concentrations, metabolism, and functions in the regulation of redox signaling. Finally, Dr. Maria Hatzoglou described how the stress-induced increases in amino acid transport, mammalian target of rapamycin (mTOR) signaling, and protein synthesis in pancreatic beta-cells can contribute to the progression of diabetes

(56) Bassett L, Troncy E, Robichaud A, Schuessler TF, Pouliot M, Ascah A, et al. Reprint of "Non-invasive measure of respiratory mechanics and conventional respiratory parameters in conscious large animals by high frequency Airwave Oscillometry". J Pharmacol Toxicol Methods 2014 Nov;70(3):283-6. Abstract: INTRODUCTION: A number of drugs in clinical trials are discontinued due to potentially life-threatening airway obstruction. As some drugs may not cause changes in core battery parameters such as tidal volume (Vt), respiratory rate (RR) or minute ventilation (MV), including measurements of respiratory mechanics in safety pharmacology studies represents an opportunity for design refinement. The present study aimed to test a novel non-invasive methodology to concomitantly measure respiratory system resistance (Rrs) and conventional respiratory parameters (Vt, RR, MV) in conscious Beagle dogs and

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cynomolgus monkeys. METHODS: An Airwave Oscillometry system (tremoFlo; THORASYS Inc., Montreal, Canada) was used to concomitantly assess Rrs and conventional respiratory parameters before and after intravenous treatment with a bronchoactive agent. Respiratory mechanics measurements were performed by applying a short (i.e. 16s) single high frequency (19Hz) waveform at the subject's airway opening via a face mask. During measurements, pressure and flow signals were recorded. After collection of baseline measurements, methacholine was administered intravenously to Beagle dogs (n=6) and cynomolgus monkeys (n=4) at 8 and 68mug/kg, respectively. RESULTS: In dogs, methacholine induced significant increases in Vt, RR and MV while in monkeys, it only augmented RR. A significant increase in Rrs was observed after methacholine administration in both species with mean percentage peak increases from baseline of 88 (53)% for dogs and 28 (16)% for cynomolgus monkeys. CONCLUSION: Airwave Oscillometry appears to be a promising non-invasive methodology to enable respiratory mechanics measurements in conscious large animals, a valuable refinement in respiratory safety pharmacology

(57) Legon AC, Walker NR. Halogen Bonding in the Gas Phase: A Comparison of the Iodine Bond in Bcdots, three dots, centeredICl and Bcdots, three dots, centeredICF for Simple Lewis Bases B. Top Curr Chem 2014 Dec 3. Abstract: Methods for observing the rotational spectra of the halogen-bonded complexes Bcdots, three dots, centeredICl and Bcdots, three dots, centeredICF3 (B=N2, CO, HC identical withCH, H2C=CH2, H2O, H2S, PH3 or NH3) and deriving from them properties such as angular geometry, radial geometry, the strength of the intermolecular bond, and the extent of electron redistribution on complex formation are described. Comparison of various properties reveals several similarities between the two series. Thus, the Bcdots, three dots, centeredICF3 obey a set of rules which originally proposed to rationalise the angular geometries of hydrogen-bonded complexes of the type Bcdots, three dots, centeredHX, but which were subsequently found to apply to their halogen-bonded analogues Bcdots, three dots, centeredXY, where XY is a dihalogen molecule, including ICl. Important for establishing the validity of these rules in both series Bcdots, three dots, centeredICl and Bcdots, three dots, centeredICF3 were the complexes with B=H2O or H2S. The configuration at O in H2Ocdots, three dots, centeredICF3 and H2Ocdots, three dots, centeredICl is effectively planar. On the other hand, the configuration at S in H2Scdots, three dots, centeredICF3 and H2Scdots, three dots, centeredICl is permanently pyramidal. Ab initio calculations of potential energy functions for inversion at O or S performed at the CCSD(T)(F12c)/cc-pVDZ-F12 level of theory confirmed these conclusions. Comparison of the intermolecular stretching force constants k sigma show that the series Bcdots, three dots, centeredICF3 is systematically more weakly bound than Bcdots, three dots, centeredICl. Interpretation of k sigma in terms of nucleophilicities N B of B and electrophilicities E IR of ICl and ICF3 reveals that [Formula: see text]. Experimental and ab initio values of distances r(Zcdots, three dots, centeredI), where Z is the acceptor atom/region of B, show that, for a given B, the intermolecular bond of Bcdots, three dots, centeredICF3 is longer than that of Bcdots, three dots, centeredICl. The electronic charge redistributed from B to ICF3 on formation of Bcdots, three dots, centeredICF3 is probably going to be negligibly small

(58) Zheng K, Lin W, Tan L, Cheng D. A two-photon fluorescent probe with a large turn-on signal for imaging hydrogen sulfide in living tissues. Anal Chim Acta 2015 Jan 1;853:548-54. Abstract: A two-photon fluorescence turn-on H2S probe GCTPOC-H2S based on a two-photon platform with a large cross-section, GCTPOC, and a sensitive H2S recognition site, dinitrophenyl ether was constructed. The probe GCTPOC-H2S exhibits desirable properties such as high sensitivity, high selectivity, functioning well at physiological pH and low cytotoxicity. In particular, the probe shows a 120-fold enhancement in the presence of Na2S (500muM), which is larger than the reported two-photon fluorescent H2S probes. The large fluorescence enhancement of the two-photon probe GCTPOC-H2S renders it attractive for imaging H2S in living tissues with deep tissue penetration. Significantly, we

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have demonstrated that the probe GCTPOC-H2S is suitable for fluorescence imaging of H2S in living tissues with deep penetration by using two-photon microscopy. The further application of the two-photon probe for the investigation of biological functions and pathological roles of H2S in living systems is under progress

(59) Pandey S. Hydrogen sulfide: a new node in the abscisic Acid-dependent guard cell signaling network? Plant Physiol 2014 Dec;166(4):1680-1.

(60) Hensley K, Denton TT. Alternative functions of the brain transsulfuration pathway represent an underappreciated aspect of brain redox biochemistry with significant potential for therapeutic engagement. Free Radic Biol Med 2015 Jan;78C:123-34. Abstract: Scientific appreciation for the subtlety of brain sulfur chemistry has lagged, despite understanding that the brain must maintain high glutathione (GSH) to protect against oxidative stress in tissue that has both a high rate of oxidative respiration and a high content of oxidation-prone polyunsaturated fatty acids. In fact, the brain was long thought to lack a complete transsulfuration pathway (TSP) for cysteine synthesis. It is now clear that not only does the brain possess a functional TSP, but brain TSP enzymes catalyze a rich array of alternative reactions that generate novel species including the gasotransmitter hydrogen sulfide (H2S) and the atypical amino acid lanthionine (Lan). Moreover, TSP intermediates can be converted to unusual cyclic ketimines via transamination. Cell-penetrating derivatives of one such compound, lanthionine ketimine (LK), have potent antioxidant, neuroprotective, neurotrophic, and antineuroinflammatory actions and mitigate diverse neurodegenerative conditions in preclinical rodent models. This review will explore the source and function of alternative TSP products, and lanthionine-derived metabolites in particular. The known biological origins of lanthionine and its ketimine metabolite will be described in detail and placed in context with recent discoveries of a GSH- and LK-binding brain protein called LanCL1 that is proving essential for neuronal antioxidant defense; and a related LanCL2 homolog now implicated in immune sensing and cell fate determinations. The review will explore possible endogenous functions of lanthionine metabolites and will discuss the therapeutic potential of lanthionine ketimine derivatives for mitigating diverse neurological conditions including Alzheimers disease, stroke, motor neuron disease, and glioma

(61) Sheu YT, Chen SC, Chien CC, Chen CC, Kao CM. Application of a long-lasting colloidal substrate with pH and hydrogen sulfide control capabilities to remediate TCE-contaminated groundwater. J Hazard Mater 2015 Mar 2;284:222-32. Abstract: A long-lasting emulsified colloidal substrate (LECS) was developed for continuous carbon and nanoscale zero-valent iron (nZVI) release to remediate trichloroethylene (TCE)-contaminated groundwater under reductive dechlorinating conditions. The developed LECS contained nZVI, vegetable oil, surfactants (Simple Green and lecithin), molasses, lactate, and minerals. An emulsification study was performed to evaluate the globule droplet size and stability of LECS. The results show that a stable oil-in-water emulsion with uniformly small droplets (0.7mum) was produced, which could continuously release the primary substrates. The emulsified solution could serve as the dispensing agent, and nZVI particles (with diameter 100-200nm) were distributed in the emulsion evenly without aggregation. Microcosm results showed that the LECS caused a rapid increase in the total organic carbon concentration (up to 488mg/L), and reductive dechlorination of TCE was significantly enhanced. Up to 99% of TCE (with initial concentration of 7.4mg/L) was removed after 130 days of operation. Acidification was prevented by the production of hydroxide ion by the oxidation of nZVI. The formation of iron sulfide reduced the odor from produced hydrogen sulfide. Microbial analyses reveal that dechlorinating bacteria existed in soils, which might contribute to TCE dechlorination

(62) Auguet O, Pijuan M, Guasch-Balcells H, Borrego CM, Gutierrez O. Implications of Downstream Nitrate Dosage in anaerobic sewers to control sulfide and methane emissions. Water Res 2014 Oct 18;68C:522-32.

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Abstract: Nitrate (NO3-) is commonly dosed in sewer systems to reduce sulfide (H2S) and methane (CH4) produced in anaerobic rising main pipes. However, anoxic conditions along the whole rising pipes are difficult and costly to maintain since nitrate is added at the upstream sections of the sewer. In this study we tested the effects of the Downstream Nitrate Dosage strategy (DND) in anaerobic pipes in a specially designed laboratory-scale systems that mimics a real rising main. Effectiveness of the strategy was assessed on H2S and CH4 abatement on the effluent of the lab sewer system. A combination of process (Normal Functioning monitoring and batch tests) and molecular (by 454-pyrosequencing) methods were used to investigate the impacts and microbial activities related to the nitrate addition. Results showed a complete abatement of H2S generated, with a fraction transformed to elemental sulfur (S0). Methane discharged was reduced to 50% while nitrate was added, due to the CH4 oxidation in the anoxic conditions established at the end of the pipe. Both sulfidogenic and methanogenic activities resumed upon cessation of NO3- dosage. An increase of microorganisms of the genera Simplicispira, Comamonas, Azonexus and Thauera was detected during nitrate addition. Regarding anoxic methane oxidation, only one Operational Taxonomic Unit (OTU) was identified, which is likely related with this metabolism. Obtained results are relevant for the optimal management of nitrate dosage strategies in sewer systems

(63) Lu S, Chen L, Huang Q, Yang L, Du C, Li X, et al. Decomposition of ammonia and hydrogen sulfide in simulated sludge drying waste gas by a novel non-thermal plasma. Chemosphere 2014 Nov 14;117C:781-5. Abstract: To efficiently clean NH3 and H2S contained in municipal sewage sludge drying waste gas, experiments were conducted with a novel gliding arc discharge plasma reactor. Important parameters including applied voltage and gas velocity which can strongly influence the removal efficiency, energy cost and by-products yields were investigated. Maximum removal efficiencies were all obtained at the applied voltage of 11kV and gas velocity of 4.72ms-1. When NH3 and H2S were treated together, the total energy cost decreased by 38%. NO and SO2 were observed as main decomposition by-products, and the presence of NH3 may inhibit the production of SO2 whose yield decreased from 223.8 to 27.8mgm-3. Tests performed on lab scale reactor showed that gliding arc discharge is efficient in decreasing the NH3 and H2S concentrations, and experiments will also be conducted on a larger scale reactor in the future

(64) d'Emmanuele d, V, Mitidieri E, Donnarumma E, Tramontano T, Brancaleone V, Cirino G, et al. Hydrogen sulfide is involved in dexamethasone-induced hypertension in rat. Nitric Oxide 2014 Nov 25. Abstract: Glucocorticoid (GC)-induced hypertension is a common clinical problem still poorly understood. The presence of GC receptor (GR) in vascular smooth muscle and endothelial cells suggests a direct role for GC in vasculature. In response to hemodynamic shear stress, endothelium tonically releases nitric oxide (NO), endothelial-derived hyperpolarizing factor (EDHF) and prostacyclin contributing to vascular homeostasis. Recently, hydrogen sulfide (H2S) has been proposed as a candidate for EDHF. H2S is endogenously mainly formed from L-cysteine by the action of cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE). It plays many physiological roles and contributes to cardiovascular function. Here we have evaluated the role played by H2S in mesenteric arterial bed and in carotid artery harvested from rats treated with vehicle or dexamethasone (DEX; 1.5 mg/kg/day) for 8 days. During treatments systolic blood pressure was significantly increased in conscious rats. EDHF contribution was evaluated in ex-vivo by performing a concentration-response curve induced by acetylcholine (Ach) in presence of a combination of indomethacin and L-NG-Nitroarginine methyl ester in both vascular districts. EDHF-mediated relaxation was significantly reduced in DEX-treated group in both mesenteric bed and carotid artery. EDHF-mediated relaxation was abolished by pre-treatment with both apamin and charybdotoxin, inhibitors of small and big calcium-dependent potassium channels respectively, or with propargylglycine, inhibitor of CSE. Western blot analysis revealed a marked reduction in CBS and CSE expression as

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well as H2S production in homogenates of mesenteric arterial bed and carotid artery from DEX-treated rats. In parallel, H2S plasma levels were significantly reduced in DEX group compared with vehicle. In conclusion, an impairment in EDHF/H2S signaling occurs in earlier state of GC-induced hypertension in rats suggesting that counteracting this dysfunction may be beneficial to manage DEX-associated increase in blood pressure

(65) Kida K, Marutani E, Nguyen RK, Ichinose F. Inhaled hydrogen sulfide prevents neuropathic pain after peripheral nerve injury in mice. Nitric Oxide 2014 Nov 24. Abstract: Increasing evidence suggests that the pathogenesis of neuropathic pain is mediated through activation of microglia in the spinal cord. Hydrogen sulfide attenuates microglial activation and central nervous system inflammation; however, the role of hydrogen sulfide in neuropathic pain is unclear. In this study, we examined the effects of hydrogen sulfide breathing on neuropathic pain in mice. C57BL/6J mice were subjected to chronic constriction injury (CCI) of the sciatic nerve. After CCI, mice breathed air alone or air mixed with hydrogen sulfide at 40 ppm for 8 h on 7 consecutive days. The expression levels of inflammatory cytokines including interleukin 6 (IL-6) were measured in the spinal cord. Effects of hydrogen sulfide on IL-6-induced activation of microglia were examined in primary rat microglia. Mice that breathed air alone exhibited the neuropathic pain behavior including mechanical allodynia and thermal hyperalgesia and increased mRNA levels of IL-6 and chemokine CC motif ligand 2 (CCL2) after CCI. Inhaled hydrogen sulfide prevented the neuropathic pain behavior and attenuated the upregulation of inflammatory cytokines. Sodium sulfide inhibited IL-6-induced activation of primary microglia. These results suggest that inhaled hydrogen sulfide prevents the development of neuropathic pain in mice possibly via inhibition of the activation of microglia in the spinal cord

(66) Veeranki S, Tyagi SC. Role of hydrogen sulfide in skeletal muscle biology and metabolism. Nitric Oxide 2014 Nov 25. Abstract: Hydrogen sulfide (H2S) is a novel endogenous gaseous signal transducer (gasotransmitter). Its emerging role in multiple facets of inter- and intra-cellular signaling as a metabolic, inflammatory, neuro and vascular modulator has been increasingly realized. Although H2S is known for its effects as an anti-hypertensive, anti-inflammatory and anti-oxidant molecule, the relevance of these effects in skeletal muscle biology during health and during metabolic syndromes is unclear. H2S has been implicated in vascular relaxation and vessel tone enhancement, which might lead to mitigation of vascular complications caused by the metabolic syndromes. Metabolic complications may also lead to mitochondrial remodeling by interfering with fusion and fission, therefore, leading to mitochondrial mitophagy and skeletal muscle myopathy. Mitochondrial protection by H2S enhancing treatments may mitigate deterioration of muscle function during metabolic syndromes. In addition, H2S might upregulate uncoupling proteins and might also cause browning of white fat, resulting in suppression of imbalanced cytokine signaling caused by abnormal fat accumulation. Likewise, as a source for H+ ions, it has the potential to augment anaerobic ATP synthesis. However, there is a need for studies to test these putative H2S benefits in different patho-physiological scenarios before its full-fledged usage as a therapeutic molecule. The present review highlights current knowledge with regard to exogenous and endogenous H2S roles in skeletal muscle biology, metabolism, exercise physiology and related metabolic disorders, such as diabetes and obesity, and also provides future directions

(67) Okamoto M, Ishizaki T, Kimura T. Protective effect of hydrogen sulfide on pancreatic beta-cells. Nitric Oxide 2014 Nov 13. Abstract: Hydrogen sulfide (H2S) is recognized as a third gaseous signaling molecule behind nitric oxide (NO) and carbon monoxide (CO). In pancreatic beta-cells, H2S inhibits glucose-induced insulin release. There are multiple underlying mechanisms for this inhibitory process. Apart from these inhibitory effects, H2S also protects pancreatic islets from apoptotic cell death induced by high glucose. Moreover, expression of the H2S-producing enzyme, cystathionine gamma-lyase (CSE), is induced by glucose

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stimulation. These observations suggest that H2S is produced in an inducible manner, as are the other two gaseous signaling molecules, NO and CO. We recently reported that a lack of CSE induces apoptotic beta-cell death and promotes the development of high-fat diet (HFD)-induced diabetes. These findings tempt us to suggest that H2S produced by CSE is part of a homeostatic mechanism used by pancreatic beta-cells to inhibit insulin release and reduce cellular stress evoked by glucose, possibly via the anti-oxidant properties of H2S

(68) Shimamoto K, Hanaoka K. Fluorescent probes for hydrogen sulfide (HS) and sulfane sulfur and their applications to biological studies. Nitric Oxide 2014 Nov 13. Abstract: Hydrogen sulfide (H2S), a toxic gas with the smell of rotten eggs, plays key roles in many physiological processes, including relaxation of vascular smooth muscles, mediation of neurotransmission, inhibition of insulin signaling, and regulation of inflammation. The most commonly used methods or detecting H2S are the methylene blue method and the electrode method, but these methods require destructive sampling, e.g., homogenization of biological samples. On the other hand, the fluorescence detection method has been widely used in biological studies to study the physiological roles of H2S, because this technology provides real-time, easy-to-use, nondestructive detection in live cells or tissues. Many selective fluorescent probes for H2S have been reported. Sulfane sulfur compounds contain divalent sulfur atoms bonded to other sulfur atom(s), as in persulfides (RSSH) and polysulfides (RSSnSR). They are currently attracting increasing interest because one of the mechanisms of activity regulation of proteins by H2S is sulfhydration of cysteine residues (RSH-->RSSH). Since H2S and sulfane sulfur are redox partners, they are very likely to coexist in biological systems, and from a reactivity point-of-view, sulfane sulfur seems likely to be much more effective than H2S in S-sulfhydration. Therefore, sulfane sulfur may be involved in mediating at least some of the biological activities of H2S. In this review, we summarize recent work on fluorescent probes selective for H2S and/or sulfane sulfur, and we briefly review their applications to biological studies

(69) Gemici B, Elsheikh W, Feitosa KB, Costa KP, Muscara MN, Wallace JL. HS-releasing drugs: anti-inflammatory, cytoprotective and chemopreventative potential. Nitric Oxide 2014 Nov 18. Abstract: Hydrogen sulfide exerts a number of cytoprotective and anti-inflammatory effects in many organ systems. In an effort to exploit these potent and beneficial effects, a number of hydrogen sulfide-releasing derivatives of existing drugs have been developed and extensively tested in pre-clinical models. In particular, efforts have been made by several groups to develop hydrogen sulfide-releasing derivatives of a number of nonsteroidal anti-inflammatory drugs. The main goal of this approach is to reduce the gastrointestinal ulceration and bleeding caused by this class of drugs, particularly when used chronically such as in the treatment of arthritis. However, these drugs may also have utility for prevention of various types of cancer. This paper provides an overview of some of the mechanisms underlying the anti-inflammatory and cytoprotective actions of hydrogen sulfide. It also gives some examples of hydrogen sulfide-releasing anti-inflammatory drugs, and their actions in terms of reducing inflammation and attenuating the development of cancer in experimental models

(70) Wu D, Hu Q, Liu X, Pan L, Xiong Q, Zhu YZ. Hydrogen sulfide protects against apoptosis under oxidative stress through SIRT1 pathway in H9c2 cardiomyocytes. Nitric Oxide 2014 Nov 25. Abstract: Oxidative stress plays a great role in the pathogenesis of heart failure (HF). Oxidative stress results in apoptosis, which can cause the damage of cardiomyocytes. Hydrogen sulfide (H2S), the third gasotransmitter, is a good reactive oxygen species (ROS) scavenger, which has protective effect against HF. Sirtuin-1 (SIRT1) is a highly conserved nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase that plays a critical role in promoting cell survival under oxidative stress. The purpose of this article is to

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investigate the interaction between H2S and SIRT1 under oxidative stress in H9c2 cardiomyocytes. Oxidative stress was induced by hydrogen peroxide (H2O2). Treatment with NaSH (25-100 micromol/L) dose-dependently increased the cell viability and improved the cell apoptosis induced by H2O2 in H9c2 cardiomyocytes. The protective effect of NaSH against the apoptosis could be attenuated by SIRT1 inhibitor Ex 527 (10 micromol/L). Treatment with NaSH (100 micromol/L) could increase the expression of SIRT1 in time dependent manner, which decreased by different concentration of H2O2. NaSH (100 micromol/L) increased the cellular ATP level and the expression of ATPase. These effects were attenuated by Ex 527 (10 micromol/L). After NaSH (100 micromol/L) treatment, the decrease in ROS production and the enhancement in SOD, GPx and GST expression were observed. Ex 527 (10 micromol/L) reversed these effects. In conclusion, for the first time, this article can identify antioxidative effects of H2S under oxidative stress through SIRT1 pathway in H9c2 cardiomyocytes

(71) Li X, Cheng J, Gong Y, Yang B, Hu Y. Mapping hydrogen sulfide in rats with a novel azo-based fluorescent probe. Biosens Bioelectron 2014 Oct 14;65C:302-6. Abstract: We report herein a reaction-based fluorescent switch-on sulfide sensor, azo3, for the quantification of endogenous sulfides in rat tissues. The sensor was exploited based on the novel azo-sulfide chemistry and designed by locking the rhodol fluorophore into its nonfluorescent form with an azo group. However, the azo group would undergo a specific and biocompatible reaction with sulfides, triggering significant fluorescence increasements which were linear to the concentrations of sulfides. Azo3 distinguished by its high sensitivity (148-fold fluorescent switch-on response), good selectivity (22-fold more selective towards sulfides than other bio-thiol species) and low detection limit (500nM). Moreover, the azo3-based assay for biological sulfides displayed the unique advantage of being insusceptible to ultraviolet (UV) irradiation. Azo3 has been successfully applied to the quantification of endogenous sulfides in rat plasma and tissues including heart, brain, liver, spleen, lung and kidney. In addition to providing azo3 as a valuable tool to analyze sulfides in biological samples, we also discussed the influences of the electron effect on the sensitivity of the probes, which would shed some light on the design of future reaction-based probes

(72) Takeuchi K, Ise F, Takahashi K, Aihara E, Hayashi S. HS-induced HCO secretion in the rat stomach - Involvement of nitric oxide, prostaglandins, and capsaicin-sensitive sensory neurons. Nitric Oxide 2014 Nov 7. Abstract: Hydrogen sulfide (H2S) is known to be an important gaseous mediator that affects various functions under physiological and pathological conditions. We examined the effects of NaHS, a H2S donor, on

(73) Snijder PM, Frenay AR, Koning AM, Bachtler M, Pasch A, Kwakernaak AJ, et al. Sodium thiosulfate attenuates angiotensin II-induced hypertension, proteinuria and renal damage. Nitric Oxide 2014 Nov 15;42:87-98. Abstract: Hypertension and proteinuria are important mediators of renal damage. Despite therapeutic interventions, the number of patients with end stage renal disease steadily increases. Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter with vasodilatory, anti-inflammatory and antioxidant properties. These beneficial characteristics make H2S an attractive candidate for pharmacological use in hypertensive renal disease. We investigated the protective properties of H2S in angiotensin II (Ang II)-induced hypertensive renal disease in rats. Treatment with the H2S donor NaHS and major H2S metabolite sodium thiosulfate (STS) during three weeks of Ang II infusion reduced hypertension, proteinuria, oxidative stress and renal functional and structural deterioration. In an ex vivo isolated perfused kidney setup, NaHS, but not STS, reduced intrarenal pressure. The effect of NaHS could partially be explained by its activation of the ATP-sensitive potassium channels. In conclusion, treatment with H2S attenuates Ang II-associated functional and structural renal deterioration, suggesting that intervention in

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H2S production pathways has potential therapeutic benefit and might be a valuable addition to the already existing antihypertensive and renoprotective therapies

(74) Kimura H. H2S2014 in Kyoto the 3 international conference on HS in biology and medicine. Nitric Oxide 2014 Oct 14. Abstract: About 20 years ago, a pungent gas was found to be the physiological mediator of cognitive function and vascular tone. Since then, studies on hydrogen sulfide (H2S) have uncovered its numerous physiological roles such as protecting various tissues/organs from ischemia and regulating inflammation, cell growth, oxygen sensing, and senescence. These effects of H2S were extensively studied, and some of the corresponding mechanisms were also studied in detail. Previous studies on the synergistic interaction between H2S and nitric oxide (NO) have led to the discovery of several potential signaling molecules. Polysulfides are considerably potent and are one of the most active forms of H2S. H2S has a significant therapeutic potential, which is evident from the large number of novel H2S-donating compounds and substances developed for manipulating endogenous levels of H2S. The Third International Conference on H2S was held in Kyoto in June 2014. One hundred and sixty participants from 21 countries convened in Kyoto to report new advances, discuss conflicting findings, and make plans for future research. This article summarizes each oral presentation presented at the conference

(75) Fang H, Jing T, Liu Z, Zhang L, Jin Z, Pei Y. Hydrogen sulfide interacts with calcium signaling to enhance the chromium tolerance in Setaria italica. Cell Calcium 2014 Oct 23;56(6):472-81. Abstract: The oscillation of intracellular calcium (Ca2+) concentration is a primary event in numerous biological processes in plants, including stress response. Hydrogen sulfide (H2S), an emerging gasotransmitter, was found to have positive effects in plants responding to chromium (Cr6+) stress through interacting with Ca2+ signaling. While Ca2+ resemblances H2S in mediating biotic and abiotic stresses, crosstalk between the two pathways remains unclear. In this study, Ca2+ signaling interacted with H2S to produce a complex physiological response, which enhanced the Cr6+ tolerance in foxtail millet (Setaria italica). Results indicate that Cr6+ stress activated endogenous H2S synthesis as well as Ca2+ signaling. Moreover, toxic symptoms caused by Cr6+ stress were strongly moderated by 50muM H2S and 20mM Ca2+. Conversely, treatments with H2S synthesis inhibitor and Ca2+ chelators prior to Cr6+-exposure aggravated these toxic symptoms. Interestingly, Ca2+ upregulated expression of two important factors in metal metabolism, MT3A and PCS, which participated in the biosynthesis of heavy metal chelators, in a H2S-dependent manner to cope with Cr6+ stress. These findings also suggest that the H2S dependent pathway is a component of the Ca2+ activating antioxidant system and H2S partially contributes Ca2+-activating antioxidant system

(76) Borron SW, Bebarta VS. Asphyxiants. Emerg Med Clin North Am 2015 Feb;33(1):89-115. Abstract: Asphyxiants deprive the body of oxygen. Simple asphyxiants displace oxygen from the lungs, whereas systemic asphyxiants interfere with transport of oxygen by hemoglobin or with mitochondrial oxidative phosphorylation. Asphyxiants may be gases, liquids, or solids, or their metabolites. The typical clinical picture of asphyxiant poisoning is one of progressive mental status changes, alteration of breathing, progressively abnormal vital signs, coma, seizures, and eventually cardiovascular collapse and death. Treatment of asphyxiant poisoning is aggressive supportive care, with control of the airway and ventilation and maintenance of cardiac output. Supportive care is often enhanced by the administration of specific antidotes

(77) Tsubota M, Kawabata A. Role of hydrogen sulfide, a gasotransmitter, in colonic pain and inflammation. Yakugaku Zasshi 2014;134(12):1245-52. Abstract: Hydrogen sulfide (H2S), the third known gaseous transmitter following nitric oxide and carbon monoxide, is generated by multiple enzymes including cystathionine-gamma-lyase (CSE) in vivo. We previously demonstrated that H2S activates

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Cav3.2 T-type Ca(2+) channels expressed on sensory neurons, leading to hyperalgesia and facilitation of inflammation. Here, we describe the role of H2S in processing of colonic pain and inflammation. Intracolonic (i.col.) administration of NaHS, an H2S donor, to mice evoked colonic pain-like nociceptive behavior and referred hyperalgesia accompanied by phosphorylation of ERK in the superficial layers of spinal dorsal horn, a marker for excitation of nociceptive neurons. The pronociceptive effect of NaHS was abolished by inhibitors or knockdown of Cav3.2 and by an inhibitor of TRPA1, another target molecule of H2S. In rats with colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS), on the other hand, repeated i.col. administration of NaHS prevented colonic ulcer and inflammatory symptoms, which were inhibited by ablation of capsaicin-sensitive sensory neurons or T-type Ca(2+) channel inhibitor. NaHS, given i.col., caused phosphorylation of ERK in the spinal dorsal horn of rats with TNBS-induced colitis, but not of naive rats. In TNBS-treated rats, Cav3.2 was upregulated in the dorsal root ganglia, while CSE was downregulated in the colon. Taken together, these findings suggest that inhibitors of the CSE/H2S/Cav3.2 or TRPA1 pathways might be useful for the treatment of colonic pain diseases such as irritable bowel syndrome, while H2S donors or Cav3.2 activators might be useful for the treatment of inflammatory bowel disease including Crohn's disease

(78) Nishida M, Toyama T, Kumagai Y, Numaga-Tomita T. Establishment of a novel therapeutic strategy for heart failure based on the mechanism underlying maintenance of redox homeostasis by reactive sulfur species. Yakugaku Zasshi 2014;134(12):1239-43. Abstract: Cardiac redox homeostasis is precisely regulated by reactive oxygen species (ROS) or electrophilic molecules that are formed by ROS reacting with intracellular substrates, and their eliminating systems. We have focused on the role of nitric oxide (NO) generated from inducible NO synthase (iNOS) that is continuously upregulated from early stage of heart failure, and revealed that iNOS-derived NO acts as a protective factor in the early stage of heart failure, whereas it contributes to induction of cardiac early senescence in later stages. The switching mechanism of NO-mediated signaling includes formation of endogenous NO-derived electrophilic byproducts such as 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), which selectively targets an oncogenic small GTPase H-Ras at Cys-184, leading to cardiac cell senescence via covalent modification (S-guanylation) and activation of H-Ras. We also found that hydrogen sulfide-related reactive sulfur species (RSS) function as potent nucleophiles to eliminate electrophilic modification of H-Ras and suppress the onset of chronic heart failure after myocardial infarction. Our results strongly suggest a new concept of redox biology in which suppression of electrophilic irreversible modification of protein cysteine thiols by RSS may be a new therapeutic strategy of cardiovascular diseases

(79) Salomone S, Foresti R, Villari A, Giurdanella G, Drago F, Bucolo C. Regulation of vascular tone in rabbit ophthalmic artery: Cross talk of endogenous and exogenous gas mediators. Biochem Pharmacol 2014 Oct 29;92(4):661-8. Abstract: Nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H2S) modulate vascular tone. In view of their therapeutic potential for ocular diseases, we examined the effect of exogenous CO and H2S on tone of isolated rabbit ophthalmic artery and their interaction with endogenous and exogenous NO. Ophthalmic artery segments mounted on a wire myograph were challenged with cumulative concentrations of phenylephrine (PE) in the presence or absence of NG-nitro-l-arginine (LNNA) to inhibit production of NO, the CO-releasing molecules CORMs or the H2S-donor GYY4137. The maximal vasoconstriction elicited by PE reached 20-30% of that induced by KCl but was dramatically increased by incubation with LNNA. GYY4137 significantly raised PE-mediated vasoconstriction, but it did not change the response to PE in the presence of LNNA or the relaxation to sodium nitroprusside (SNP). CORMs concentration-dependently inhibited PE-induced constriction, an effect that was synergistic with endogenous NO (reduced by LNNA), but insensitive to blockade of guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3,-alpha]quinoxalin-1-one (ODQ). In vascular tissues cyclic GMP (cGMP) levels seemed reduced by GYY4137 (not significantly), but were not changed by

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CORM. These data indicate that CO is able per se to relax isolated ophthalmic artery and to synergize with NO, while H2S counteracts the effect of endogenous NO. CO does not stimulate cGMP production in our system, while H2S may reduce cGMP production stimulated by endogenous NO. These findings provide new insights into the complexities of gas interactions in the control of ophthalmic vascular tone, highlighting potential pharmacological targets for ocular diseases

(80) Lobb I, Sonke E, Aboalsamh G, Sener A. Hydrogen sulphide and the kidney: Important roles in renal physiology and pathogenesis and treatment of kidney injury and disease. Nitric Oxide 2014 Oct 24. Abstract: The kidney is an essential mammalian organ that serves to filter toxins and metabolic by-products out of the blood, which are then excreted through urine. Hydrogen sulphide (H2S) is a recently characterized, endogenous gaseous molecule with important physiological roles. Many interesting roles continue to be identified for H2S related specifically to the kidney. The current review discusses how production and action of H2S influences normal physiology of the kidney. We investigate as well the many roles H2S plays in the pathogenesis and treatment of kidney injury and disease, such as chronic kidney disease (CKD), ureteral obstruction (UO), hyperhomocysteinaemia (HHcy), drug-induced nephrotoxicity (DIN) and renal ischaemia reperfusion injury (IRI). We suggest that H2S plays a complex and essential role in the normal function of the kidney and dysregulation of H2S production can directly or indirectly contribute to the pathogenesis of renal disease and injury. Also, H2S could be a promising potential therapeutic treatment to decrease the severity of several renal diseases. Further research will identify increasingly important and complex roles for H2S in renal physiology and how H2S can be effectively utilized to improve clinical outcomes of renal disease

(81) Li G, Xie ZZ, Chua JM, Wong PC, Bian J. Hydrogen sulfide protects testicular germ cells against heat-induced injury. Nitric Oxide 2014 Oct 24. Abstract: OBJECTIVE: The present study was designed to investigate whether H2S can protect testicular germ cells against heat exposure induced injury and the underlying mechanisms. RESULTS: It was found that all three H2S generating enzymes, cystathionine beta-synthase (CBS), cystathionine gamma-lysase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST), were expressed in mouse testicular tissue. Three episodes of heat exposure (42 degrees C, 30 min/day, 3 days) significantly decreased endogenous H2S production and down-regulated the expression of CBS and CSE in testes. In primary cultured testicular germ cells, exogenous application of NaHS (an H2S donor) attenuated heat stress (42 degrees C, 30 min) induced cell death and apoptosis. This was mediated by the inhibitory effects of H2S on cytochrome C release and the ratio of the Bax/Bcl-2. NaHS also improved mitochondrial function by decreasing oxygen consumption and increasing ATP production. NaHS treatment also stimulated SOD activity and reduced ROS production. CONCLUSIONS: Our results revealed both physiological and pharmacological roles of H2S in testicular germ cells. Exogenous application of H2S may protect germ cells by preservation of mitochondrial function and stimulation of anti-oxidant activity

(82) Ohno K, Okuda K, Uehara T. Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide. Biochem Biophys Res Commun 2015 Jan 2;456(1):245-9. Abstract: Hydrogen sulfide (H2S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H2S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and the oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H2S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine beta-synthetase (CBS) using

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siRNA decreased this modification in a manner that was correlated to amount of H2S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H2S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions

(83) Yang M, Huang Y, Chen J, Chen YL, Ma JJ, Shi PH. Activation of AMPK participates hydrogen sulfide-induced cyto-protective effect against dexamethasone in osteoblastic MC3T3-E1 cells. Biochem Biophys Res Commun 2014 Oct 14;454(1):42-7. Abstract: Long-time glucocorticoids (GCs) usage causes osteoporosis. In the present study, we explored the potential role of hydrogen sulfide (H2S) against dexamethasone (Dex)-induced osteoblast cell damage, and focused on the underlying mechanisms. We showed that two H2S-producing enzymes, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), were significantly downregulated in human osteonecrosis tissues as well as in Dex-treated osteoblastic MC3T3-E1 cells. H2S donor NaHS as well as the CBS activator S-adenosyl-l-methionine (SAM) inhibited Dex-induced viability reduction, death and apoptosis in MC3T3-E1 cells. NaHS activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling, which participated its cyto-protective activity. AMPK inhibition by its inhibitor (compound C) or reduction by targeted-shRNA suppressed its pro-survival activity against Dex in MC3T3-E1 cells. Further, we found that NaHS inhibited Dex-mediated reactive oxygen species (ROS) production and ATP depletion. Such effects by NaHS were again inhibited by compound C and AMPKalpha1-shRNA. In summary, we show that H2S inhibits Dex-induced osteoblast damage through activation of AMPK signaling. H2S signaling might be further investigated as a novel target for anti-osteoporosis treatment

(84) Das A, Durrant D, Salloum FN, Xi L, Kukreja RC. PDE5 inhibitors as therapeutics for heart disease, diabetes and cancer. Pharmacol Ther 2014 Oct 31. Abstract: The phosphodiesterase 5 (PDE5) inhibitors, including sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) have been developed for treatment of erectile dysfunction. Moreover, sildenafil and tadalafil are used for the management of pulmonary arterial hypertension in patients. Since our first report showing the cardioprotective effect of sildenafil in 2002, there has been tremendous growth of preclinical and clinical studies on the use of PDE5 inhibitors for cardiovascular diseases and cancer. Numerous animal studies have demonstrated that PDE5 inhibitors have powerful protective effect against myocardial ischemia/reperfusion (I/R) injury, doxorubicin cardiotoxicity, ischemic and diabetic cardiomyopathy, cardiac hypertrophy, Duchenne muscular dystrophy and the improvement of stem cell efficacy for myocardial repair. Mechanistically, PDE5 inhibitors protect the heart against I/R injury through increased expression of nitric oxide synthases, activation of protein kinase G (PKG), PKG-dependent hydrogen sulfide generation, and phosphorylation of glycogen synthase kinase-3beta - a master switch immediately proximal to mitochondrial permeability transition pore and the end effector of cardioprotection. In addition, PDE5 inhibitors enhance the sensitivity of certain types of cancer to standard chemotherapeutic drugs, including doxorubicin. Many clinical trials with PDE5 inhibitors have focused on the potential cardiovascular and anti-cancer benefits. Despite mixed results of these clinical trials, there is a continuing strong interest by basic scientists and clinical investigators in exploring their new clinical uses. It is our hope that future new mechanistic investigations and carefully designed clinical trials would help in reaping additional benefits of PDE5 inhibitors for cardiovascular disease and cancer in patients

(85) Olas B. Hydrogen sulfide in signaling pathways. Clin Chim Acta 2015 Jan 15;439C:212-8. Abstract: For a long time hydrogen sulfide (H2S) was considered a toxic compound, but recently H2S (at low concentrations) has been found to play an important function in physiological processes. Hydrogen sulfide, like other well-known compounds - nitric oxide (NO) and carbon monoxide (CO) is a gaseous intracellular signal transducer. It regulates the cell cycle, apoptosis and the oxidative stress. Moreover, its functions include neuromodulation, regulation of cardiovascular system and inflammation. In this review, I

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focus on the metabolism of hydrogen sulfide (including enzymatic pathways of H2S synthesis from l- and d-cysteine) and its signaling pathways in the cardiovascular system and the nervous system. I also describe how hydrogen sulfide may be used as therapeutic agent, i.e. in the cardiovascular diseases

(86) Coletti R, meida-Pereira G, Elias LL, ntunes-Rodrigues J. Effects of hydrogen sulfide (HS) on water intake and vasopressin and oxytocin secretion induced by fluid deprivation. Horm Behav 2014 Nov 29;67C:12-20. Abstract: During dehydration, responses of endocrine and autonomic control systems are triggered by central and peripheral osmoreceptors and peripheral baroreceptors to stimulate thirst and sodium appetite. Specifically, it is already clear that endocrine system acts by secreting vasopressin (AVP), oxytocin (OT) and angiotensin II (ANG II), and that gaseous molecules, such as nitric oxide (NO) and carbon monoxide (CO), play an important role in modulating the neurohypophyseal secretion as well as ANG II production and thirst. More recently, another gas-hydrogen sulfide (H2S)-has been studied as a neuronal modulator, which is involved in hypothalamic control of blood pressure, heart frequency and temperature. In this study, we aimed to investigate whether H2S and its interaction with NO system could participate in the modulatory responses of thirst and hormonal secretion induced by fluid deprivation. For this purpose, Wistar male rats were deprived of water for 12 and 24h, and the activity of sulfide-generating enzymes was measured. Surprisingly, 24-h water deprivation increased the activity of sulfide-generating enzymes in the medial basal hypothalamus (MBH). Furthermore, the icv injection of sodium sulfide (Na2S, 260nmol), a H2S donor, reduced water intake, increased AVP, OT and CORT plasma concentrations and decreased MBH nitrate/nitrite (NOX) content of 24-h water-deprived animals compared to controls. We thus suggest that H2S system has an important role in the modulation of hormonal and behavioral responses induced by 24-h fluid deprivation

(87) Duan F, Li Y, Chen L, Zhou X, Chen J, Chen H, et al. Sulfur inhibits the growth of androgen-independent prostate cancer. Oncol Lett 2015 Jan;9(1):437-41. Abstract: Sulfur is a bright yellow crystalline solid at room temperature. The aim of the present study was to investigate the inhibitory effect of sulfur on prostate cancer (PCa) in vivo. Prostate tumors were developed by injecting 22Rv1 or DU-145 PCa cells into sulfur-treated or untreated nude mice. The weight and volume of the tumors were measured. The cancer cells were separated from the tumors, and analyzed for their growth rate and clonogenicity in culture. The expression of PCa-targeted genes was also assessed using real-time polymerase chain reaction. The rate of growth of 22Rv1 tumors in sulfur-treated nude mice gradually decreased, and was reduced by 41.99% (P<0.01) after 22 days when compared with that of the control group. In addition, the growth of DU-145 tumors was also suppressed by 75.16% (P<0.05) after 11 weeks. The clonogenicity of the sulfur-treated tumor cells decreased by 36.7% when compared with that of the control cells. However, no significant difference in cell growth was identified. mRNA levels of the androgen-receptor, prostate specific antigen and human Hox (NKX3.1) genes were significantly decreased by 32.8, 48.2 and 42.2% in sulfur-treated tumors, respectively. Additionally, it was found that the hydrogen sulfide concentration in the serum of sulfur-treated mice was increased by 4.73% (P<0.05). Sulfur significantly suppressed the growth of PCa in vivo. Since sulfur is a known ingredient used in traditional Chinese medicine, it may be used clinically for the treatment of PCa, independently or in combination with other medicine

(88) Mir S, Sen T, Sen N. Cytokine-Induced GAPDH Sulfhydration Affects PSD95 Degradation and Memory. Mol Cell 2014 Dec 18;56(6):786-95. Abstract: Induction of a proinflammatory cytokine, interleukin-1beta (IL-1beta) plays a role in memory impairment associated with various neurological disorders and brain injury. Here we show that IL-1beta-induced memory impairment in brain is mediated by hydrogen sulfide (H2S) synthesized by cystathionine beta-synthase (CBS). H2S modifies GAPDH

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essentially via sulfhydration in dendrites, which promotes its binding to the E3 ligase protein, Siah. Then Siah binds to a critical synaptic scaffolding molecule, PSD95, and leads it to degradation via ubiquitination. In CBS heterozygous mice (cbs(+/-)) and primary neurons depleted with either CBS or IL-1R, IL-1beta-induced loss of PSD95 was rescued along with a decrease in the level of GAPDH sulfhydration. Moreover, decrease in the loss of PSD95 in cbs(+/-) mice results in improvement of IL-1beta-induced cognitive deficits and neurobehavioral outcomes. Thus, our findings reveal a mechanism where GAPDH sulfhydration appears to be a physiologic determinant of cytokine-induced memory impairment in brain

(89) Fernandez D, Legrand M, Abujaber S, Nelson LS. Letter in response to "The Vitamin B12 analog cobinamide is an effective hydrogen sulfide antidote in a lethal rabbit model". Clin Toxicol (Phila) 2015 Jan;53(1):73.

(90) Lin YH, Chen YC, Chu H. The mechanism of coal gas desulfurization by iron oxide sorbents. Chemosphere 2015 Feb;121:62-7. Abstract: This study aims to understand the roles of hydrogen and carbon monoxide during the desulfurization process in a coal gasification system that H2S of the syngas was removed by Fe2O3/SiO2 sorbents. The Fe2O3/SiO2 sorbents were prepared by incipient wetness impregnation. Through the breakthrough experiments and Fourier transform infrared spectroscopy analyses, the overall desulfurization mechanism of the Fe2O3/SiO2 sorbents was proposed in this study. The results show that the major reaction route is that Fe2O3 reacts with H2S to form FeS, and the existence of CO and H2 in the simulated gas significantly affects equilibrium concentrations of H2S and COS. The formation of COS occurs when the feeding gas is blended with CO and H2S, or CO2 and H2S. The pathways in the formation of products from the desulfurization process by the reaction of Fe2O3 with H2S have been successfully established