Acido solfidrico nella letteratura internazionale Studi inseriti in PubMed nel mese di luglio 2015

(aggiornamento al 7 agosto 2015)

(1) Tocmo R, Liang D, Wang C, Poh J, Huang D. Organosulfide profile and hydrogen sulfide-releasing capacity of stinky bean (Parkia speciosa) oil: Effects of pH and extraction methods. Food Chem 2016 Jan 1;190:1123-9. Abstract: Stinky beans (Parkia speciosa) were hydrodistilled and solvent-extracted and the oil obtained was analyzed by GC-MS/FID. Nine cyclic and one acyclic organosulfides were identified comprising 36% of total volatiles. Solvent extracts contained significantly (p<0.05) higher total organosulfides (680ppm) as compared to distilled oil (444ppm). The concentrations of organosulfides are highly dependent on the pH values of the matrix, with control sample (pH 5.40) giving the highest total organosulfides (424ppm) followed by that of pH 7.0 (234ppm), pH 9.0 (195ppm), and pH 3.0 (152ppm). The H2S-releasing capacity, expressed as diallyl trisulfide equivalents (DATS-E in mmol DATS/g), corresponded well with the differences in organosulfide concentrations as affected by pH with control having the highest value (24.35) followed pH 7.0 (7.27), pH 9.0 (3.27), and pH 3.0 (1.80). We conclude that stinky bean oil is a potent H2S-releasing agent that could have health-beneficial properties

(2) Othonos KM, Zervos M, Christofides C, Othonos A. Ultrafast Spectroscopy and Red Emission from beta-Ga2O 3/beta-Ga 2S 3 Nanowires. Nanoscale Res Lett 2015 Dec;10(1):1016. Abstract: Ultrafast pump-probe and transient photoluminescence spectroscopy were used to investigate carrier dynamics in beta-Ga2O3 nanowires converted to beta-Ga2O3/Ga2S3 under H2S between 400 to 600 degrees C. The beta-Ga2O3 nanowires exhibited broad blue emission with a lifetime of 2.4 ns which was strongly suppressed after processing at 500-600 degrees C giving rise to red emission centered at 680 nm with a lifetime of 19 mus. Differential absorption spectroscopy reveals that state filling occurs in states located below the conduction band edge before sulfurization, but free carrier absorption is dominant in the beta-Ga2O3/Ga2S3 nanowires processed at 500 to 600 degrees C for probing wavelengths >500 nm related to secondary excitation of the photo-generated carriers from the mid-gap states into the conduction band of Ga2S3

(3) Wu C, Zhou Y, Wang P, Guo S. Improving hydrolysis acidification by limited aeration in the pretreatment of petrochemical wastewater. Bioresour Technol 2015 Oct;194:256-62. Abstract: Petrochemical wastewater was pretreated by hydrolysis acidification to improve the biodegradation and treatability on limited aeration conditions. The results showed limited aeration with DO from 0.2 to 0.3mg/L (average ORP was -210mV) was the best condition. The BOD5/COD of influent was 0.23, and it increased to 0.43 on this condition. Limited aeration can obviously reduce the reduction of SO4(2-), reducing the generation of toxic gas H2S, and almost no H2S can be detected in the off-gas. The sulfate reducing bacteria (SRB) diversity and abundance on limited aeration condition was obviously inhibited. Limited aeration condition was benefit for the removal of benzene ring organics, such as benzene, toluene, ethylbenzene and xylenes (BTEX), improving the toxicity and treatability of the wastewater. Based on the experiment results, an anaerobic hydrolysis acidification tank (100,000m(3)) has been transformed into limited aeration hydrolysis acidification tank and it runs well

2

(4) Liao H, Kadjo AF, Dasgupta PK. Concurrent High-Sensitivity Conductometric Detection of Volatile Weak Acids in a Suppressed Anion Chromatography System. Anal Chem 2015 Aug 5. Abstract: A suppressed hydroxide eluent anion chromatograph effluent flows through the outside of a gas-permeable membrane tube while electrogenerated 100-200 muM LiOH flows through the lumen into a second conductivity detector. Undissociated volatile acid eluites (e.g., H2S, HCN, H2CO3, etc., represented as HA) transfer through the membrane and react as OH- + HA --> A- + H2O; the conversion of high-mobility OH- to lower mobility A- results in a significant negative response for these analytes. With the chromatograph operated at a macroscale (0.3 mL/min) the LiOH flow can be 3-30-fold lower, resulting in corresponding enrichment of the transferred analyte prior to detection. Because there is no mixing of liquids, the detector noise is very low (<0.1 nS/cm), comparable to the principal chromatographic detector. Thus, despite a background of 25-45 muS/cm, limits of detection for sulfide and cyanide are in the submicromolar level, with a linear dynamic range up to 100 muM. Carbonate/bicarbonate can also be sensitively detected. We demonstrate adaptation in a standard commercial system. We also show that Microsoft Excel-based numerical simulations of transport quantitatively predict the observed behavior well

(5) Feng W, Teo XY, Novera W, Ramanujulu PM, Liang D, Huang D, et al. Discovery of New HS Releasing Phosphordithioates and 2,3-Dihydro-2-phenyl-2-sulfanylenebenzo[d][1,3,2]oxazaphospholes with Improved Antiproliferative Activity. J Med Chem 2015 Aug 5. Abstract: Hydrogen sulfide (H2S) is now recognized as a physiologically important gasotransmitter. Compounds which release H2S slowly are sought after for their potential in therapy. Herein the synthesis of a series of phosphordithioates based on 1 (GYY4137) are described. Their H2S release profiles are characterized using 2,6-dansyl azide (2), an H2S specific fluorescent probe. Most compounds have anticancer activity in several solid tumor cell lines and are less toxic in a normal human lung fibroblast, WI38. A preferred compound, 14, with 10-fold greater anticancer activity than 1, was shown to release H2S in MCF7 cells using a cell active probe, 21. Both permeability and intracellular pH (pHi) were found to be significantly improved for 14 compared to 1. Furthermore, 14 was also negative in the AMES test for genotoxicity. Cyclization of these initial structures gave a series of 2,3-dihydro-2-phenyl-2-sulfanylenebenzo[d][1,3,2]oxazaphospholes, of which the simplest member, compound 22 (FW1256), was significantly more potent in cells. The improved therapeutic window of 22 in WI38 cells was compared with three other cell types. Potency of 22 was superior to 1 in MCF7 tumor spheroids and the mechanism of cell death was shown to be via apoptosis with an increase in cleaved PARP and activated caspase-7. Evidence of H2S release in cells is also presented. This work provides a "toolbox" of slow-release H2S donors useful for studies of H2S in biology and as potential therapeutics in cancer, inflammation, and cardiovascular disease

(6) Hu J, Yin G, Chen J, Ge M, Lu J, Yang Z, et al. An olive-shaped SnO2 nanocrystal-based low concentration H2S gas sensor with high sensitivity and selectivity. Phys Chem Chem Phys 2015 Aug 28;17(32):20537-42. Abstract: Olive-shaped SnO2 nanocrystals were synthesized successfully via a facile hydrothermal route, using tin dichloride hydrate, oxalic acid dihydrate and polyvinylpyrrolidone as reaction precursors, and showed great potential in the large-scale preparation of SnO2 nanocrystals. The prepared SnO2 nanocrystals were characterized using XRD, XPS, SEM, TEM and HRTEM, and showed well-defined olive-shaped tetragonal single-crystals with irregular exposed facets. The growth mechanism of the olive-shaped SnO2 nanocrystals was considered after investigating the experimental conditions and reaction time. Due to the abundant active sites on the irregular surfaces, the gas sensing performance of the prepared SnO2 nanocrystals exhibited great gas sensing properties, including high sensitivity, selectivity and stability towards H2S with a very low detection limit (less than 0.5 ppm), revealing their great potential in commercial applications for H2S gas detection

3

(7) Hippler M. Cavity-Enhanced Raman Spectroscopy of Natural Gas with Optical Feedback cw-Diode Lasers. Anal Chem 2015 Aug 4;87(15):7803-9. Abstract: We report on improvements made on our previously introduced technique of cavity-enhanced Raman spectroscopy (CERS) with optical feedback cw-diode lasers in the gas phase, including a new mode-matching procedure which keeps the laser in resonance with the optical cavity without inducing long-term frequency shifts of the laser, and using a new CCD camera with improved noise performance. With 10 mW of 636.2 nm diode laser excitation and 30 s integration time, cavity enhancement achieves noise-equivalent detection limits below 1 mbar at 1 bar total pressure, depending on Raman cross sections. Detection limits can be easily improved using higher power diodes. We further demonstrate a relevant analytical application of CERS, the multicomponent analysis of natural gas samples. Several spectroscopic features have been identified and characterized. CERS with low power diode lasers is suitable for online monitoring of natural gas mixtures with sensitivity and spectroscopic selectivity, including monitoring H2, H2S, N2, CO2, and alkanes

(8) Zhang L, Zhu H, Li M, Gu X. A novel fluorescent probe for imaging endogenous hydrogen sulphide via the CSE enzymatic pathway. Chem Commun (Camb ) 2015 Aug 4;51(66):13135-7. Abstract: In this paper, we developed a novel fluorescent probe for endogenous H2S detection. In the probe , the fast responding and highly selective reaction site towards H2S, incorporating the membrane permeable BODIPY fluorescent dye, enables the probe to be applied for the detection of endogenous H2S via the CSE enzymatic pathway

(9) Carter JM, Qian Y, Foster JC, Matson JB. Peptide-based hydrogen sulphide-releasing gels. Chem Commun (Camb ) 2015 Aug 4;51(66):13131-4. Abstract: An aromatic peptide amphiphile was designed for delivery of the signaling gas H2S. The peptide self-assembled in water into nanofibers that gelled upon charge screening. The non-toxic gel slowly released H2S over 15 hours, and the presence of H2S in endothelial cells was verified using a fluorescent H2S probe

(10) Roman P, Veltman R, Bijmans MF, Keesman KJ, Janssen AJ. Effect of Methanethiol Concentration on Sulfur Production in Biological Desulfurization Systems under Haloalkaline Conditions. Environ Sci Technol 2015 Aug 4;49(15):9212-21. Abstract: Bioremoval of H2S from gas streams became popular in recent years because of high process efficiency and low operational costs. To expand the scope of these processes to gas streams containing volatile organic sulfur compounds, like thiols, it is necessary to provide new insights into their impact on overall biodesulfurization process. Published data on the effect of thiols on biodesulfurization processes are scarce. In this study, we investigated the effect of methanethiol on the selectivity for sulfur production in a bioreactor integrated with a gas absorber. This is the first time that the inhibition of biological sulfur formation by methanethiol is investigated. In our reactor system, inhibition of sulfur production started to occur at a methanethiol loading rate of 0.3 mmol L(-1) d(-1). The experimental results were also described by a mathematical model that includes recent findings on the mode of biomass inhibition by methanethiol. We also found that the negative effect of methanethiol can be mitigated by lowering the salinity of the bioreactor medium. Furthermore, we developed a novel approach to measure the biological activity by sulfide measurements using UV-spectrophotometry. On the basis of this measurement method, it is possible to accurately estimate the unknown kinetic parameters in the mathematical model

(11) Gao L, Xu Z, Yin Z, Chen K, Wang C, Zhang H. Association of hydrogen sulfide with alterations of monocyte chemokine receptors, CCR2 and CX3CR1 in patients with coronary artery disease. Inflamm Res 2015 Aug;64(8):627-35. Abstract: OBJECTIVES: Recent data in human and mice suggest that monocyte chemokine receptors CX3CR1 and CCR2 are involved in the pathogenesis of

4

atherosclerosis. Our previous study showed that hydrogen sulfide, a novel gaseous mediator hampered the progression of atherosclerosis in fat-fed apoE(-/-) mice with downregulating CX3CR1 and CX3CL1 expressions. However, there is a paucity of information regarding the clinical association between endogenous H2S metabolism and alterations of monocyte chemokine receptors in patients with cardiovascular disease. Therefore, in this study, we investigated circulating monocyte heterogeneity with differential expressions of CCR2 and CX3CR1 and its relevance to plasma H2S level in patients with coronary artery disease (CAD). METHODS: Sixty-three CAD patients with acute coronary syndrome (ACS, n = 46) or stable angina pectoris (SAP, n = 17) undergoing either percutaneous coronary intervention or coronary angiography and eleven non-CAD patients were enrolled in the study. Plasma levels of H2S as well as chemokines (CCL2 and CX3CL1) and expressions of CCR2 and CX3CR1 on peripheral monocytes were measured. RESULTS: It was found that plasma H2S level was significantly reduced, whereas plasma CCL2 and CX3CL1 levels were substantially elevated in patients with ACS, as compared with patients with SAP or non-CAD patients. Furthermore, patients with ACS had significantly higher proportion of CD14(+)CCR2(+)CX3CR1(+) and CD14(+)CCR2(-)CX3CR1(+) monocytes but lower percentage of CD14(+)CCR2(+)CX3CR1(-) monocytes than SAP or non-CAD patients did. Lastly, plasma H2S level showed a significantly negative correlation with the proportion of CD14(+)CCR2(+)CX3CR1(+) monocytes, but not other monocyte subsets. CONCLUSIONS: These data indicate that decreased endogenous H2S production may predispose stable CAD patients to rupture of vulnerable plaque and thus to ACS, probably in relation to circulating monocyte phenotypic transformation with differential expressions of CCR2 and CX3CR1

(12) Pyeon JJ, Cho CJ, Baek SH, Kang CY, Kim JS, Jeong DS, et al. Control of the initial growth in atomic layer deposition of Pt films by surface pretreatment. Nanotechnology 2015 Jul 31;26(30):304003. Abstract: The controllability of the nucleation behavior of Pt in atomic layer deposition (ALD) by surface pretreatments with H2O, H2S, and NH3 was investigated. The H2O pretreatment on SiO2 and TiO2 surfaces had little effect on the nucleation of Pt. The H2S pretreatment on the SiO2 and TiO2 surfaces significantly delayed the nucleation of Pt on them, while the NH3 pretreatment on the TiO2 surface led to fluent nucleation of Pt. In particular, a continuous Pt film was successfully formed even at an ultrathin thickness of approximately 2.2 nm by NH3 pretreatment. This work suggests that the pretreatment with H2S and NH3 is an efficient way to control the nucleation of Pt in ALD without the support of any reactive species, such as plasma or O3. Such a strategy enables the easy control of the size and distribution density of Pt nanoparticles for a wide range of applications

(13) Shen J, Keithly ME, Armstrong RN, Higgins KA, Edmonds KA, Giedroc DP. Staphylococcus aureus CstB Is a Novel Multidomain Persulfide Dioxygenase-Sulfurtransferase Involved in Hydrogen Sulfide Detoxification. Biochemistry 2015 Jul 28;54(29):4542-54. Abstract: Hydrogen sulfide (H2S) is both a lethal gas and an emerging gasotransmitter in humans, suggesting that the cellular H2S level must be tightly regulated. CstB is encoded by the cst operon of the major human pathogen Staphylococcus aureus and is under the transcriptional control of the persulfide sensor CstR and H2S. Here, we show that CstB is a multifunctional Fe(II)-containing persulfide dioxygenase (PDO), analogous to the vertebrate protein ETHE1 (ethylmalonic encephalopathy protein 1). Chromosomal deletion of ethe1 is fatal in vertebrates. In the presence of molecular oxygen (O2), hETHE1 oxidizes glutathione persulfide (GSSH) to generate sulfite and reduced glutathione. In contrast, CstB oxidizes major cellular low molecular weight (LMW) persulfide substrates from S. aureus, coenzyme A persulfide (CoASSH) and bacillithiol persulfide (BSSH), directly to generate thiosulfate (TS) and reduced thiols, thereby avoiding the cellular toxicity of sulfite. Both Cys201 in the N-terminal PDO domain (CstB(PDO)) and Cys408 in the C-terminal rhodanese domain (CstB(Rhod)) strongly enhance the TS generating activity of CstB. CstB

5

also possesses persulfide transferase (PT; reverse rhodanese) activity, which generates TS when provided with LMW persulfides and sulfite, as well as conventional thiosulfate transferase (TST; rhodanese) activity; both of these activities require Cys408. CstB protects S. aureus against H2S toxicity, with the C201S and C408S cstB genes being unable to rescue a NaHS-induced DeltacstB growth phenotype. Induction of the cst operon by NaHS reveals that functional CstB impacts cellular TS concentrations. These data collectively suggest that CstB may have evolved to facilitate the clearance of LMW persulfides that occur upon elevation of the level of cellular H2S and hence may have an impact on bacterial viability under H2S misregulation, in concert with the other enzymes encoded by the cst operon

(14) Cowley ES, Kopf SH, LaRiviere A, Ziebis W, Newman DK. Pediatric Cystic Fibrosis Sputum Can Be Chemically Dynamic, Anoxic, and Extremely Reduced Due to Hydrogen Sulfide Formation. MBio 2015;6(4). Abstract: Severe and persistent bacterial lung infections characterize cystic fibrosis (CF). While several studies have documented the microbial diversity within CF lung mucus, we know much less about the inorganic chemistry that constrains microbial metabolic processes and their distribution. We hypothesized that sputum is chemically heterogeneous both within and between patients. To test this, we measured microprofiles of oxygen and sulfide concentrations as well as pH and oxidation-reduction potentials in 48 sputum samples from 22 pediatric patients with CF. Inorganic ions were measured in 20 samples from 12 patients. In all cases, oxygen was depleted within the first few millimeters below the sputum-air interface. Apart from this steep oxycline, anoxia dominated the sputum environment. Different sputum samples exhibited a broad range of redox conditions, with either oxidizing (16 mV to 355 mV) or reducing (-300 to -107 mV) potentials. The majority of reduced samples contained hydrogen sulfide and had a low pH (2.9 to 6.5). Sulfide concentrations increased at a rate of 0.30 microM H2S/min. Nitrous oxide was detected in only one sample that also contained sulfide. Microenvironmental variability was observed both within a single patient over time and between patients. Modeling oxygen dynamics within CF mucus plugs indicates that anoxic zones vary as a function of bacterial load and mucus thickness and can occupy a significant portion of the mucus volume. Thus, aerobic respiration accounts only partially for pathogen survival in CF sputum, motivating research to identify mechanisms of survival under conditions that span fluctuating redox states, including sulfidic environments. IMPORTANCE: Microbial infections are the major cause of morbidity and mortality in people living with CF, and yet microbial growth and survival in CF airways are not well understood. Insufficient information about the chemistry of the in vivo environment contributes to this knowledge gap. Our documentation of variable redox states corresponding to the presence or absence of sulfide begins to fill this void and motivates understanding of how different opportunistic pathogens adapt in these dynamic environments. Given the changing chemical state of CF sputum over time, it is important to consider a spectrum of aerobic and anaerobic lifestyles when studying CF pathogens in the laboratory. This work not only provides relevant constraints that can shape the design of laboratory experiments, it also suggests that sulfide might be a useful proxy for assessing the redox state of sputum in the clinic

(15) Chen J, Wang WH, Wu FH, He EM, Liu X, Shangguan ZP, et al. Hydrogen sulfide enhances salt tolerance through nitric oxide-mediated maintenance of ion homeostasis in barley seedling roots. Sci Rep 2015;5:12516. Abstract: Hydrogen sulfide (H2S) and nitric oxide (NO) are emerging as messenger molecules involved in the modulation of plant physiological processes. Here, we investigated a signalling network involving H2S and NO in salt tolerance pathway of barley. NaHS, a donor of H2S, at a low concentration of either 50 or 100 muM, had significant rescue effects on the 150 mM NaCl-induced inhibition of plant growth and modulated the K(+)/Na(+) balance by decreasing the net K(+) efflux and increasing the gene expression of an inward-rectifying potassium channel (HvAKT1) and a high-affinity K(+) uptake system (HvHAK4). H2S and NO maintained the lower Na(+) content in the cytoplast by increasing

6

the amount of PM H(+)-ATPase, the transcriptional levels of PM H(+)-ATPase (HvHA1) and Na(+)/H(+) antiporter (HvSOS1). H2S and NO modulated Na(+) compartmentation into the vacuoles with up-regulation of the transcriptional levels of vacuolar Na(+)/H(+) antiporter (HvVNHX2) and H(+)-ATPase subunit beta (HvVHA-beta) and increased in the protein expression of vacuolar Na(+)/H(+) antiporter (NHE1). H2S mimicked the effect of sodium nitroprusside (SNP) by increasing NO production, whereas the function was quenched with the addition of NO scavenger. These results indicated that H2S increased salt tolerance by maintaining ion homeostasis, which were mediated by the NO signal

(16) Huang B, Chen CT, Chen CS, Wang YM, Hsieh HJ, Wang DL. Laminar shear flow increases hydrogen sulfide and activates a nitric oxide producing signaling cascade in endothelial cells. Biochem Biophys Res Commun 2015 Jul 26. Abstract: Laminar shear flow triggers a signaling cascade that maintains the integrity of endothelial cells (ECs). Hydrogen sulfide (H2S), a new gasotransmitter is regarded as an upstream regulator of nitric oxide (NO). Whether the H2S-generating enzymes are correlated to the enzymes involved in NO production under shear flow conditions remains unclear as yet. In the present study, the cultured ECs were subjected to a constant shear flow (12 dyn/cm2) in a parallel flow chamber system. We investigated the expression of three key enzymes for H2S biosynthesis, cystathionine-gamma-lyase (CSE), cystathionine-beta-synthase (CBS), and 3-mercapto-sulfurtransferase (3-MST). Shear flow markedly increased the level of 3-MST. Shear flow enhanced the production of H2S was determined by NBD-SCN reagent that can bind to cysteine/homocystein. Exogenous treatment of NaHS that can release gaseous H2S, ECs showed an increase of phosphorylation in AktS473, ERKT202/Y204 and eNOSS1177. This indicated that H2S can trigger the NO-production signaling cascade. Silencing of CSE, CBS and 3-MST genes by siRNA separately attenuated the phosphorylation levels of AktS473 and eNOSS1177 under shear flow conditions. The particular mode of shear flow increased H2S production. The interplay between H2S and NO-generating enzymes were discussed in the present study

(17) Liu C, Xu X, Gao J, Zhang T, Yang Z. Hydrogen Sulfide Prevents Synaptic Plasticity from VD-Induced Damage via Akt/GSK-3beta Pathway and Notch Signaling Pathway in Rats. Mol Neurobiol 2015 Jul 26. Abstract: Our previous study has demonstrated that hydrogen sulfide (H2S) attenuates neuronal injury induced by vascular dementia (VD) in rats, but the mechanism is still poorly understood. In this study, we aimed to investigate whether the neuroprotection of H2S was associated with synaptic plasticity and try to interpret the potential underlying mechanisms. Adult male Wistar rats were suffered the ligation of bilateral common carotid arteries. At 24 h after surgery, rats were administered intraperitoneally with sodium hydrosulfide (NaHS, 5.6 mg.kg-1.day-1), a H2S donor, for 3 weeks in the VD+NaHS group and treated intraperitoneally with saline in the VD group respectively. Our results demonstrated that NaHS significantly decreased the level of glutamate. It obviously ameliorated cognitive flexibility as well as the spatial learning and memory abilities by Morris water maze. Moreover, NaHS significantly improved the long-term depression (LTD), and was able to elevate the expression of N-methyl-D-aspartate receptor subunit 2A, which plays a pivotal role in synaptic plasticity. Interestingly, NaHS decreased the phosphorylation of Akt, and it could maintain the activity of glycogen synthase kinase-3beta (GSK-3beta). Surprisingly, NaHS triggered the canonical Notch pathway by increasing expressions of Jagged-1 and Hes-1. These findings suggest that NaHS prevents synaptic plasticity from VD-induced damage partly via Akt/GSK-3beta pathway and Notch signaling pathway.Hydrogen sulfide modulated the ratio of NMDAR 2A/2B and improved the synaptic plasticity via Akt/GSK-3beta pathway and Notch signaling pathway in VD rats

(18) Xia FF, Zhang HT, Wei XM, Su Y, He R. Characterization of HS removal and microbial community in landfill cover soils. Environ Sci Pollut Res Int 2015 Jul 25. Abstract: H2S is a source of odors at landfills and poses a threat to the surrounding environment and public health. In this work, compared with a usual landfill cover soil (LCS),

7

H2S removal and biotransformation were characterized in waste biocover soil (WBS), an alternative landfill cover material. With the input of landfill gas (LFG), the gas concentrations of CH4, CO2, O2, and H2S, microbial community and activity in landfill covers changed with time. Compared with LCS, lower CH4 and H2S concentrations were detected in the WBS. The potential sulfur-oxidizing rate and sulfate-reducing rate as well as the contents of acid-volatile sulfide, SO4 2-, and total sulfur in the WBS and LCS were all increased with the input of LFG. After exposure to LFG for 35 days, the sulfur-oxidizing rate of the bottom layer of the WBS reached 82.5 mumol g dry weight (d.w.)-1 day-1, which was 4.3-5.4 times of that of LCS. H2S-S was mainly deposited in the soil covers, while it escaped from landfills to the atmosphere. The adsorption, absorption, and biotransformation of H2S could lead to the decrease in the pH values of landfill covers; especially, in the LCS with low pH buffer capacity, the pH value of the bottom layer dropped to below 4. Pyrosequencing of 16S ribosomal RNA (rRNA) gene showed that the known sulfur-metabolizing bacteria Ochrobactrum, Paracoccus, Comamonas, Pseudomonas, and Acinetobacter dominated in the WBS and LCS. Among them, Comamonas and Acinetobacter might play an important role in the metabolism of H2S in the WBS. These findings are helpful to understand sulfur bioconversion process in landfill covers and to develop techniques for controlling odor pollution at landfills

(19) Aykan A, Ozturk S, Sahin I, Avcu F, Sagkan RI, Isik S. The Effects of Hydrogen Sulfide on Adipocyte Viability in Human Adipocyte and Adipocyte-Derived Mesenchymal Stem Cell Cultures Under Ischemic Conditions. Ann Plast Surg 2015 Jul 23. Abstract: BACKGROUND: This study evaluated the in vitro effects of hydrogen sulfide on adipocyte survival under ischemic conditions and explored possible mechanisms of its apoptotic process. METHODS: The mesenchymal stem cell culture was prepared from a human subcutaneous adipose tissue sample. Adipose-derived mesenchymal stem cells were differentiated into the adipogenic direction, and a mature adipocyte culture was obtained. The adipose-derived mesenchymal stem cell and mature adipocyte cultures were both divided into 6 groups. Sodium hydrogen sulfide was used as a hydrogen sulfide donor. After treating the groups with sodium hydrogen sulfide (0, 0.1, 1, 10, 100, and 1000 muM), the cell cultures were incubated in 1% oxygen at 37 degrees C for 24 hours. After the ischemia period, the cell culture groups were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test for the proliferation/cytotoxicity rates, flow cytometry for apoptosis and necrosis rates, and reverse transcriptase polymerase chain reaction for apoptotic (Bax, Caspase-3) and antiapoptotic (Bcl-2) gene expression levels. RESULTS: Statistically significant increases in proliferation rates were found in mesenchymal stem cell groups treated with low dose (0, 1, and 1 muM) sodium hydrogen sulfide (P < 0.05). For each dose, a statistically significant decrease was found in late apoptosis levels on the mature adipocyte cultures (P < 0.05). In both cell culture groups, Bcl-2 gene expression was increased and Caspase-3 gene expression was decreased. CONCLUSIONS: Under ischemic conditions, hydrogen sulfide has a protective effect on mesenchymal stem cells and mature adipocytes, and this effect is mediated by the elevation of antiapoptotic gene expression

(20) Chen J, Wu FH, Shang YT, Wang WH, Hu WJ, Simon M, et al. Hydrogen sulphide improves adaptation of Zea mays seedlings to iron deficiency. J Exp Bot 2015 Jul 23. Abstract: Hydrogen sulphide (H2S) is emerging as a potential molecule involved in physiological regulation in plants. However, whether H2S regulates iron-shortage responses in plants is largely unknown. Here, the role of H2S in modulating iron availability in maize (Zea mays L. cv Canner) seedlings grown in iron-deficient culture solution is reported. The main results are as follows: Firstly, NaHS, a donor of H2S, completely prevented leaf interveinal chlorosis in maize seedlings grown in iron-deficient culture solution. Secondly, electron micrographs of mesophyll cells from iron-deficient maize seedlings revealed plastids with few photosynthetic lamellae and rudimentary grana. On the contrary, mesophyll chloroplasts appeared completely developed in H2S-treated maize seedlings. Thirdly, H2S treatment increased iron accumulation in maize seedlings by

8

changing the expression levels of iron homeostasis- and sulphur metabolism-related genes. Fourthly, phytosiderophore (PS) accumulation and secretion were enhanced by H2S treatment in seedlings grown in iron-deficient solution. Indeed, the gene expression of ferric-phytosiderophore transporter (ZmYS1) was specifically induced by iron deficiency in maize leaves and roots, whereas their abundance was decreased by NaHS treatment. Lastly, H2S significantly enhanced photosynthesis through promoting the protein expression of ribulose-1,5-bisphosphate carboxylase large subunit (RuBISCO LSU) and phosphoenolpyruvate carboxylase (PEPC) and the expression of genes encoding RuBISCO large subunit (RBCL), small subunit (RBCS), D1 protein (psbA), and PEPC in maize seedlings grown in iron-deficient solution. These results indicate that H2S is closely related to iron uptake, transport, and accumulation, and consequently increases chlorophyll biosynthesis, chloroplast development, and photosynthesis in plants

(21) Fitzpatrick J, Kim E. Synthetic Modeling Chemistry of Iron-Sulfur Clusters in Nitric Oxide Signaling. Acc Chem Res 2015 Jul 21. Abstract: Nitric oxide (NO) is an important signaling molecule that is involved in many physiological and pathological functions. Iron-sulfur proteins are one of the main reaction targets for NO, and the [Fe-S] clusters within these proteins are converted to various iron nitrosyl species upon reaction with NO, of which dinitrosyl iron complexes (DNICs) are the most prevalent. Much progress has been made in identifying the origin of cellular DNIC generation. However, it is not well-understood which other products besides DNICs may form during [Fe-S] cluster degradation nor what effects DNICs and other degradation products can have once they are generated in cells. Even more elusive is an understanding of the manner by which cells cope with unwanted [Fe-S] modifications by NO. This Account describes our synthetic modeling efforts to identify cluster degradation products derived from the [2Fe-2S]/NO reaction in order to establish their chemical reactivity and repair chemistry. Our intent is to use the chemical knowledge that we generate to provide insight into the unknown biological consequences of cluster modification. Our recent advances in three different areas are described. First, new reaction conditions that lead to the formation of previously unrecognized products during the reaction of [Fe-S] clusters with NO are identified. Hydrogen sulfide (H2S), a gaseous signaling molecule, can be generated from the reaction between [2Fe-2S] clusters and NO in the presence of acid or formal H* (e-/H+) donors. In the presence of acid, a mononitrosyl iron complex (MNIC) can be produced as the major iron-containing product. Second, cysteine analogues can efficiently convert MNICs back to [2Fe-2S] clusters without the need for any other reagents. This reaction is possible for cysteine analogues because of their ability to labilize NO from MNICs and their capacity to undergo C-S bond cleavage, providing the necessary sulfide for [2Fe-2S] cluster formation. Lastly, unique dioxygen reactivity of various types of DNICs has been established. N-bound neutral {Fe(NO)2}10 DNICs react with O2 to generate low-temperature stable peroxynitrite (ONOO-) species, which then carry out nitration chemistry in the presence of phenolic substrates, relevant to tyrosine nitration chemistry. The reaction between S-bound anionic {Fe(NO)2}9 DNICs and O2 results in the formation of Roussin's red esters (RREs) and thiol oxidation products, chemistry that may be important in biological cysteine oxidation. The N-bound cationic {Fe(NO)2}9 DNICs can spontaneously release NO, and this property can be utilized in developing a new class of NO-donating agents with anti-inflammatory activity

(22) Trabelsi T, Ajili Y, Ben YS, Jaidane NE, Mogren Al-Mogren M, Francisco JS, et al. Characterization and reactivity of the weakly bound complexes of the [H, N, S](-) anionic system with astrophysical and biological implications. J Chem Phys 2015 Jul 21;143(3):034303. Abstract: We investigate the lowest electronic states of doublet and quartet spin multiplicity states of HNS(-) and HSN(-) together with their parent neutral triatomic molecules. Computations were performed using highly accurate ab initio methods with a large basis set. One-dimensional cuts of the full-dimensional potential energy surfaces (PESs) along the interatomic distances and bending angle are presented for each isomer. Results show

9

that the ground anionic states are stable with respect to the electron detachment process and that the long range parts of the PESs correlating to the SH(-) + N, SN(-) + H, SN + H(-), NH + S(-), and NH(-) + S are bound. In addition, we predict the existence of long-lived weakly bound anionic complexes that can be formed after cold collisions between SN(-) and H or SH(-) and N. The implications for the reactivity of these species are discussed; specifically, it is shown that the reactions involving SH(-), SN(-), and NH(-) lead either to the formation of HNS(-) or HSN(-) in their electronic ground states or to autodetachment processes. Thus, providing an explanation for why the anions, SH(-), SN(-), and NH(-), have limiting detectability in astrophysical media despite the observation of their corresponding neutral species. In a biological context, we suggest that HSN(-) and HNS(-) should be incorporated into H2S-assisted heme-catalyzed reduction mechanism of nitrites in vivo

(23) Kolluru GK, Bir SC, Yuan S, Shen X, Pardue S, Wang R, et al. Cystathionine gamma-lyase regulates arteriogenesis through NO dependent monocyte recruitment. Cardiovasc Res 2015 Jul 20. Abstract: AIMS: Hydrogen sulfide (H2S) is a vasoactive gasotransmitter that is endogenously produced in the vasculature by the enzyme cystathionine gamma-lyase (CSE). However, the importance of CSE activity and local H2S generation for ischemic vascular remodeling remains completely unknown. In this study, we examine the hypothesis that CSE critically regulates ischemic vascular remodeling involving H2S dependent mononuclear cell regulation of arteriogenesis. METHODS AND RESULTS: Arteriogenesis including mature vessel density, collateral formation; blood flow and SPY angiographic blush rate were determined in WT and CSE knockout mice at different time points following femoral artery ligation (FAL). The role of endogenous H2S in regulation of IL-16 expression and subsequent recruitment of monocytes, and expression of VEGF and bFGF in ischemic tissues, were determined along with EPC (CD34/Flk1) formation and function. FAL of wild type mice significantly increased CSE activity, expression and endogenous H2S generation in ischemic tissues and monocyte infiltration, which was absent in CSE deficient mice. Treatment of CSE knockout mice with the polysulfide donor diallyl trisulfide (DATS) restored ischemic vascular remodeling, monocyte infiltration and cytokine expression. Importantly, exogenous H2S therapy restored NO bioavailability in CSEKO mice that was responsible for monocyte recruitment and arteriogenesis. CONCLUSION: Endogenous CSE/H2S regulates ischemic vascular remodeling mediated during hind limb ischemia through NO dependent monocyte recruitment and cytokine induction revealing a previously unknown mechanism of arteriogenesis

(24) Sigot L, Ducom G, Benadda B, Laboure C. Comparison of adsorbents for HS and D4 removal for biogas conversion in a solid oxide fuel cell. Environ Technol 2015 Jul 20;1-10. Abstract: Biogas contains trace compounds detrimental for solid oxide fuel cell (SOFC) application, especially sulphur-containing compounds and volatile organic silicon compounds (VOSiCs). It is therefore necessary to remove these impurities from the biogas for fuelling an SOFC. In this paper, dynamic lab-scale adsorption tests were performed on synthetic polluted gas to evaluate the performance of a polishing treatment to remove hydrogen sulphide (

(25) Bradley AS, Leavitt WD, Schmidt M, Knoll AH, Girguis PR, Johnston DT. Patterns of sulfur isotope fractionation during Microbial Sulfate Reduction. Geobiology 2015 Jul 20. Abstract: Studies of microbial sulfate reduction have suggested that the magnitude of sulfur isotope fractionation varies with sulfate concentration. Small apparent sulfur isotope fractionations preserved in Archean rocks have been interpreted as suggesting Archean sulfate concentrations of <200 mum, while larger fractionations thereafter have been interpreted to require higher concentrations. In this work, we demonstrate that fractionation imposed by sulfate reduction can be a function of concentration over a millimolar range, but that nature of this relationship depends on the organism studied. Two sulfate-reducing bacteria grown in continuous culture with sulfate concentrations ranging from 0.1 to 6 mm

10

showed markedly different relationships between sulfate concentration and isotope fractionation. Desulfovibrio vulgaris str. Hildenborough showed a large and relatively constant isotope fractionation (34 epsilonSO 4-H2S congruent with 25 per thousand), while fractionation by Desulfovibrio alaskensis G20 strongly correlated with sulfate concentration over the same range. Both data sets can be modeled as Michaelis-Menten (MM)-type relationships but with very different MM constants, suggesting that the fractionations imposed by these organisms are highly dependent on strain-specific factors. These data reveal complexity in the sulfate concentration-fractionation relationship. Fractionation during MSR relates to sulfate concentration but also to strain-specific physiological parameters such as the affinity for sulfate and electron donors. Previous studies have suggested that the sulfate concentration-fractionation relationship is best described with a MM fit. We present a simple model in which the MM fit with sulfate concentration and hyperbolic fit with growth rate emerge from simple physiological assumptions. As both environmental and biological factors influence the fractionation recorded in geological samples, understanding their relationship is critical to interpreting the sulfur isotope record. As the uptake machinery for both sulfate and electrons has been subject to selective pressure over Earth history, its evolution may complicate efforts to uniquely reconstruct ambient sulfate concentrations from a single sulfur isotopic composition

(26) Liu H, Yu T, Liu Y. Sulfate reducing bacteria and their activities in oil sands process-affected water biofilm. Sci Total Environ 2015 Jul 20;536:116-22. Abstract: Biofilm reactors were constructed to grow stratified multispecies biofilm in oil sands process-affected water (OSPW) supplemented with growth medium. The development of sulfate reducing bacteria (SRB) within the biofilm and the biofilm treatment of OSPW were evaluated. The community structure and potential activity of SRB in the biofilm were investigated with H2S microsensor measurements, dsrB gene-based denaturing gradient gel electrophoresis (DGGE), and the real time quantitative polymerase chain reaction (qPCR). Multispecies biofilm with a thickness of 1000mum was successfully developed on engineered biocarriers. H2S production was observed in the deeper anoxic zone of the biofilm from around 750mum to 1000mum below the bulk water-biofilm interface, revealing sulfate reduction in the deeper zone of the stratified biofilm. The biofilm removed chemical oxygen demand (COD), sulfate, and nitrogen. The study expands current knowledge of biofilm treatment of OSPW and the function of anaerobic SRB in OSPW biofilm, and thus provides information for future bioreactor development in the reclamation of OSPW

(27) Yamane S, Nomura R, Yanagihara M, Nakamura H, Fujino H, Matsumoto K, et al. L-cysteine/d,L-homocysteine-regulated ileum motility via system L and B degrees transporter: Modification by inhibitors of hydrogen sulfide synthesis and dietary treatments. Eur J Pharmacol 2015 Jul 19;764:471-9. Abstract: Previous studies including ours demonstrated that l-cysteine treatments decreased motility in gastrointestinal tissues including the ileum via hydrogen sulfide (H2S), which is formed from sulfur-containing amino acids such as l-cysteine and l-homocysteine. However, the amino acid transport systems involved in l-cysteine/l-homocysteine-induced responses have not yet been elucidated in detail; therefore, we investigated these systems pharmacologically by measuring electrical stimulation (ES)-induced contractions with amino acids in mouse ileum preparations. The treatments with l-cysteine and d,l-homocysteine inhibited ES-induced contractions in ileum preparations from fasted mice, and these responses were decreased by the treatment with 2-aminobicyclo[2.2.1]heptane-2-carboxylate (BCH), an inhibitor of systems L and B degrees ,+. The results obtained using ileum preparations and a model cell line (PC12 cells) with various amino acids and BCH showed that not only l-cysteine, but also aminooxyacetic acid and d,l-propargylglycine, which act as H2S synthesis inhibitors, appeared to be taken up by these preparations/cells in L and B degrees ,+ system-dependent manners. The l-cysteine and d,l-homocysteine responses were delayed and abolished, respectively, in ileum preparations from fed mice. Our results suggested

11

that the regulation of ileum motility by l-cysteine and d,l-homocysteine was dependent on BCH-sensitive systems, and varied depending on feeding in mice. Therefore, the effects of aminooxyacetic acid and d,l-propargylglycine on transport systems need to be considered in pharmacological analyses

(28) Shekhah O, Belmabkhout Y, Adil K, Bhatt PM, Cairns AJ, Eddaoudi M. A facile solvent-free synthesis route for the assembly of a highly CO selective and HS tolerant metal-organic framework. Chem Commun (Camb ) 2015 Jul 17. Abstract: The development of materials for CO2 capture with high selectivity and high tolerance to H2S is of prime importance for various industrially relevant gas streams (e.g. natural gas and biogas upgrading as well as pre-combustion capture). Here, we report the successful fabrication of a MOF with combined exceptional CO2 capture properties and H2S tolerance, namely the NiSIFSIX-based MOF using both solvothermal and solvent-free methodologies

(29) Gerasimova E, Lebedeva J, Yakovlev A, Zefirov A, Giniatullin R, Sitdikova G. Mechanisms of hydrogen sulfide (HS) action on synaptic transmission at the mouse neuromuscular junction. Neuroscience 2015 Jul 17;303:577-85. Abstract: Hydrogen sulfide (H2S) is a widespread gasotransmitter also known as a powerful neuroprotective agent in the central nervous system. However, the action of H2S in peripheral synapses is much less studied. In the current project we studied the modulatory effects of the H2S donor sodium hydrosulfide (NaHS) on synaptic transmission in the mouse neuromuscular junction using microelectrode technique. Using focal recordings of presynaptic response and evoked transmitter release we have shown that NaHS (300muM) increased evoked end-plate currents (EPCs) without changes of presynaptic waveforms which indicated the absence of NaHS effects on sodium and potassium currents of motor nerve endings. Using intracellular recordings it was shown that NaHS increased the frequency of miniature end-plate potentials (MEPPs) without changing their amplitudes indicating a pure presynaptic effect. Furthermore, NaHS increased the amplitude of end-plate potentials (EPPs) without influencing the resting membrane potential of muscle fibers. l-cysteine, a substrate of H2S synthesis induced, similar to NaHS, an increase of EPC amplitudes whereas inhibitors of H2S synthesis (beta-cyano-l-alanine and aminooxyacetic acid) had the opposite effect. Inhibition of adenylate cyclase using MDL 12,330A hydrochloride (MDL 12,330A) or elevation of cAMP level with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (pCPT-cAMP) completely prevented the facilitatory action of NaHS indicating involvement of the cAMP signaling cascade. The facilitatory effect of NaHS was significantly diminished when intracellular calcium (Ca2+) was buffered by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM) and ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid acetoxymethyl ester (EGTA-AM). Activation of ryanodine receptors by caffeine or ryanodine increased acetylcholine release and prevented further action of NaHS on transmitter release, likely due to an occlusion effect. Inhibition of ryanodine receptors by ryanodine or dantrolene also reduced the action of NaHS on EPC amplitudes. Our results indicate that in mammalian neuromuscular synapses endogenously produced H2S increases spontaneously and evoked quantal transmitter release from motor nerve endings without changing the response of nerve endings. The presynaptic effect of H2S appears mediated by intracellular Ca2+ and cAMP signaling and involves presynaptic ryanodine receptors

(30) Winther AK, Dalsgaard T, Hedegaard ER, Simonsen U. Involvement of hydrogen sulfide in perivascular and hypoxia-induced inhibition of endothelin contraction in porcine retinal arterioles. Nitric Oxide 2015 Jul 17. Abstract: Perivascular retina has been shown to regulate retinal vascular tone. In the present study, we evaluated an ex vivo retina preparation, and investigated whether hydrogen sulfide (H2S) mediates an inhibitory effect of retina and/or hypoxia on arteriolar tone. In retina, immunolabeling showed an increase of glial fibrillary acidic protein, but not

12

vimentin over time in Muller cells, and the presence of necrotic cells after 2 hrs and apoptotic cells after 8hrs. Isometric tension recordings showed endothelin-1(ET-1) to induce concentration-dependent contractions, which were reduced in the presence of retina. In arterioles with retina no change was observed in ET-1 contractions after 5 hrs compared to 8hrs. Hypoxia (1% O2) reduced ET-1 contraction in arterioles with and without retina. The H2S donor, GYY4137 and the salt, sodium hydrogen sulfide, induced concentration-dependent relaxations in ET-1 contracted retinal arterioles. Inhibition of the H2S producing enzymes, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), with carboxymethoxylamine (AOA) and L-propargylglycine (PPG) enhanced ET-1 contractions. This effect was more pronounced in hypoxic conditions. However, even in the presence of AOA and PPG ET-1 induced less contraction in the presence of perivascular retina compared to isolated vessels. These findings suggest that both the presence of perivascular retina and hypoxia reduce arteriolar vasoconstriction and that both H2S and another factor mediate this effect. Finally, H2S donors, as well as endogenous H2S, can reduce retinal arteriolar tone, suggesting a potential therapeutic role for enhanced H2S bioavailability in the treatment of retinal disease

(31) Oosterhuis NR, Frenay AS, Wesseling S, Snijder PM, Slaats GG, Yazdani S, et al. dl-propargylglycine reduces blood pressure and renal injury but increases kidney weight in angiotensin-II infused rats. Nitric Oxide 2015 Jul 17;49:56-66. Abstract: Hydrogen sulfide (H2S), carbon monoxide (CO) and nitric oxide (NO) share signaling and vasorelaxant properties and are involved in proliferation and apoptosis. Inhibiting NO production or availability induces hypertension and proteinuria, which is prevented by concomitant blockade of the H2S producing enzyme cystathionine gamma-lyase (CSE) by d,l-propargylglycine (PAG). We hypothesized that blocking H2S production ameliorates Angiotensin II (AngII)-induced hypertension and renal injury in a rodent model. Effects of concomitant administration of PAG or saline were therefore studied in healthy (CON) and AngII hypertensive rats. In CON rats, PAG did not affect systolic blood pressure (SBP), but slightly increased proteinuria. In AngII rats PAG reduced SBP, proteinuria and plasma creatinine (180 +/- 12 vs. 211 +/- 19 mmHg; 66 +/- 35 vs. 346 +/- 92 mg/24 h; 24 +/- 6 vs. 47 +/- 15 mumol/L, respectively; p < 0.01). Unexpectedly, kidney to body weight ratio was increased in all groups by PAG (p < 0.05). Renal injury induced by AngII was reduced by PAG (p < 0.001). HO-1 gene expression was increased by PAG alone (p < 0.05). PAG increased inner cortical tubular cell proliferation after 1 week and decreased outer cortical tubular nucleus number/field after 4 weeks. In vitro proximal tubular cell size increased after exposure to PAG. In summary, blocking H2S production with PAG reduced SBP and renal injury in AngII infused rats. Independent of the cardiovascular and renal effects, PAG increased HO-1 gene expression and kidney weight. PAG alone increased tubular cell size and proliferation in-vivo and in-vitro. Our results are indicative of a complex interplay of gasotransmitter signaling/action of mutually compensatory nature in the kidney

(32) Kuksis M, Ferguson AV. Actions of a hydrogen sulfide donor (NaHS) on transient sodium, persistent sodium, and voltage gated calcium currents in neurons of the subfornical organ. J Neurophysiol 2015 Jul 15;jn. Abstract: Hydrogen sulfide (H2S) is an endogenously found gasotransmitter that has been implicated in a variety of beneficial physiological functions. This study was performed to investigate the cellular mechanisms underlying actions of H2S previously observed in subfornical organ (SFO), where H2S acts to regulate blood pressure through a depolarization of the membrane and an overall increase in the excitability of SFO neurons. We used whole cell patch clamp electrophysiology in the voltage clamp configuration to analyze the effect of 1 mM NaHS, an H2S donor, on voltage gated potassium, sodium, and calcium currents. We observed no effect of NaHS on potassium currents, however both voltage gated sodium currents (persistent and transient) and the N-type calcium current had a depolarized activation curve and an enhanced peak induced current in response to a series of voltage step and ramp protocols run in the control and NaHS conditions. These

13

effects were not responsible for the previously observed depolarization of the membrane potential, as depolarizing effects of H2S were still observed following block of these conductances with TTX (5microM) and omega-conotoxin-GVIA (100nM). Our studies are the first to investigate the effect of H2S on a variety of voltage gated conductances in a single brain area, and although they do not explain mechanisms underlying the depolarizing actions of H2S on SFO neurons, they provide evidence of potential mechanisms through which this gasotransmitter influences the excitability of neurons in this important brain area as a consequence of the modulation of multiple ion channels

(33) Ronai Z, Kreizinger Z, Dan A, Drees K, Foster JT, Banyai K, et al. First isolation and characterization of Brucella microti from wild boar. BMC Vet Res 2015;11:147. Abstract: BACKGROUND: Brucella microti was first isolated from common vole (Microtus arvalis) in the Czech Republic in Central Europe in 2007. As B. microti is the only Brucella species known to live in soil, its distribution, ecology, zoonotic potential, and genomic organization is of particular interest. The present paper is the first to report the isolation of B. microti from a wild boar (Sus scrofa), which is also the first isolation of this bacterial species in Hungary. RESULTS: The B. microti isolate was cultured, after enrichment in Brucella-selective broth, from the submandibular lymph node of a female wild boar that was taken by hunters in Hungary near the Austrian border in September 2014. Histological and immunohistological examinations of the lymph node sections with B. abortus-, B. suis- and B. canis-specific sera gave negative results. The isolate did not require CO2 for growth, was oxidase, catalase, and urease positive, H2S negative, grew well in the presence of 20 mug/ml basic fuchsin and thionin, and had brownish pigmentation after three days of incubation. It gave strong positive agglutination with anti-A and anti-M but had a negative reaction with anti-R monospecific sera. The API 20 NE test identified it as Ochrobactrum anthropi with 99.9 % identity, and it showed B. microti-specific banding pattern in the Bruce- and Suis-ladder multiplex PCR systems. Whole genome re-sequencing identified 30 SNPs in orthologous loci when compared to the B. microti reference genome available in GenBank, and the MLVA analysis yielded a unique profile. CONCLUSIONS: Given that the female wild boar did not develop any clinical disease, we hypothesize that this host species only harboured the bacterium, serving as a possible reservoir capable of maintaining and spreading this pathogen. The infectious source could have been either a rodent, a carcass that had been eaten or infection occurred via the boar rooting in soil. The low number of discovered SNPs suggests an unexpectedly high level of genetic homogeneity in this Brucella species

(34) Wei X, Zhang B, Cheng L, Chi M, Deng L, Pan H, et al. Hydrogen sulfide induces neuroprotection against experimental stroke in rats by down-regulation of AQP4 via activating PKC. Brain Res 2015 Jul 11. Abstract: Hydrogen sulfide (H2S) is now known as an important neuromodulator in the central nervous system. The aim of the current study was to investigate whether exogenous H2S gas can attenuate brain edema induced by experimental stroke and to clarify the potential mechanisms. Rats underwent 2-h middle cerebral artery occlusion (MCAO) and received 40ppm or 80ppm H2S inhalation for 3h at the beginning of reperfusion. The effects of H2S were investigated by evaluating neurological function, infarct size, brain edema volume, and aquaporin4 (AQP4) protein expression at 24h after reperfusion. Moreover, to explore the possible mechanisms for the neuroprotective effects of H2S, protein kinase C (PKC) activity was detected and a PKC inhibitor, Go6983, was used via intracerebral ventricular injection. Our results showed that 40ppm or 80ppm H2S inhalation significantly reduced neurological deficits, infarct size, and brain edema after MCAO. The expression of AQP4 in the peri-infarct area of brain was also inhibited after inhalation of H2S. PKC was activated by H2S treatment and the PKC inhibitor attenuated the neuroprotection of H2S with an increased AQP4 expression at the same time. In conclusion, H2S inhalation attenuates brain edema, reduces infarct volume, and improves neurologic function in a rat experimental stroke model. The therapeutic benefits of H2S inhalation are associated with down-regulation of AQP4 expression via activating PKC

14

(35) Ujike A, Otsuguro KI, Miyamoto R, Yamaguchi S, Ito S. Bidirectional effects of hydrogen sulfide via ATP-sensitive K channels and transient receptor potential A1 channels in RIN14B cells. Eur J Pharmacol 2015 Jul 11;764:463-70. Abstract: Hydrogen sulfide (H2S) reportedly acts as a gasotransmitter because it mediates various cellular responses through several ion channels including ATP-sensitive K+ (KATP) channels and transient receptor potential (TRP) A1 channels. H2S can activate both KATP and TRPA1 channels at a similar concentration range. In a single cell expressing both channels, however, it remains unknown what happens when both channels are simultaneously activated by H2S. In this study, we examined the effects of H2S on RIN14B cells that express both KATP and TRPA1 channels. RIN14B cells showed several intracellular Ca2+ concentration ([Ca2+]i) responses to NaHS (300microM), an H2S donor, i.e., inhibition of spontaneous Ca2+ oscillations (37%), inhibition followed by [Ca2+]i increase (24%), and a rapid increase in [Ca2+]i (25%). KATP channel blockers, glibenclamide or tolbutamide, abolished any inhibitory effects of NaHS and enhanced NaHS-mediated [Ca2+]i increases, which were inhibited by extracellular Ca2+ removal, HC030031 (a TRPA1 antagonist), and disulfide bond-reducing agents. NaHS induced 5-hydroxytryptamine (5-HT) release from RIN14B cells, which was also inhibited by TRPA1 antagonists. These results indicate that H2S has both inhibitory and excitatory effects by opening KATP and TRPA1 channels, respectively, in RIN14B cells, suggesting potential bidirectional modulation of secretory functions

(36) Wang X, Xie B, Wu D, Hassan M, Huang C. Characteristics and risks of secondary pollutants generation during compression and transfer of municipal solid waste in Shanghai. Waste Manag 2015 Jul 11. Abstract: The generation and seasonal variations of secondary pollutants were investigated during three municipal solid waste (MSW) compression and transfer in Shanghai, China. The results showed that the raw wastewater generated from three MSW transfer stations had pH of 4.2-6.0, COD 40,000-70,000mg/L, BOD5 15,000-25,000mg/L, ammonia nitrogen (NH3-N) 400-700mg/L, total nitrogen (TN) 600-1500mg/L, total phosphorus (TP) 50-200mg/L and suspended solids (SS) 1000-80,000mg/L. The pH, COD, BOD5 and NH3-N did not show regular change throughout the year while the concentration of TN, TP and SS were higher in summer and autumn. The animal and vegetable oil content was extremely high. The average produced raw wastewater of three transfer stations ranged from 2.3% to 8.4% of total refuse. The major air pollutants of H2S 0.01-0.17mg/m3, NH3 0.75-1.8mg/m3 in transfer stations, however, the regular seasonal change was not discovered. During the transfer process, the generated leachate in container had pH of 5.7-6.4, SS of 9120-32,475mg/L. The COD and BOD5 were 41,633-89,060mg/L and 18,116-34,130mg/L respectively, higher than that in the compress process. The concentration of NH3-N and TP were 587-1422mg/L and 80-216mg/L, respectively, and both increased during transfer process. H2S, VOC, CH4 and NH3 were 0.4-4mg/m3, 7-19mg/m3, 0-3.4% and 1-4mg/m3, respectively. The PCA analysis showed that the production of secondary pollutants is closely related to temperature, especially CH4. Therefore, avoiding high temperature is a key means of reducing the production of gaseous pollutants. And above all else, refuse classification in source, deodorization and anti-acid corrosion are the important processes to control the secondary pollutants during compression and transfer of MSW

(37) Yu Q, Lu Z, Tao L, Yang L, Guo Y, Yang Y, et al. ROS-Dependent Neuroprotective Effects of NaHS in Ischemia Brain Injury Involves the PARP/AIF Pathway. Cell Physiol Biochem 2015 Jul 10;36(4):1539-51. Abstract: BACKGROUND/AIMS: Stroke is among the top causes of death worldwide. Neuroprotective agents are thus considered as potentially powerful treatment of stroke. METHODS: Using both HT22 cells and male Sprague-Dawley rats as in vitro and in vivo models, we investigated the effect of NaHS, an exogenous donor of H2S, on the focal cerebral ischemia-reperfusion (I/R) induced brain injury. RESULTS: Administration of NaHS significantly decreased the brain infarcted area as compared to the I/R group in a

15

dose-dependent manner. Mechanistic studies demonstrated that NaHS-treated rats displayed significant reduction of malondialdehyde content, and strikingly increased activity of superoxide dismutases and glutathione peroxidase in the brain tissues compared with I/R group. The enhanced antioxidant capacity as well as restored mitochondrial function are NaHS-treatment correlated with decreased cellular reactive oxygen species level and compromised apoptosis in vitro or in vivo in the presence of NaHS compared with control. Further analysis revealed that the inhibition of PARP-1 cleavage and AIF translocation are involved in the neuroprotective effects of NaHS. CONCLUSION: Collectively, our results suggest that NaHS has potent protective effects against the brain injury induced by I/R. NaHS is possibly effective through inhibition of oxidative stress and apoptosis. (c) 2015 S. Karger AG, Basel

(38) De VC, Relitti F, Kralj M, Covelli S, Emili A. Oxygen, carbon, and nutrient exchanges at the sediment-water interface in the Mar Piccolo of Taranto (Ionian Sea, southern Italy). Environ Sci Pollut Res Int 2015 Jul 9. Abstract: In the shallow environment, the nutrient and carbon exchanges at the sediment-water interface contribute significantly to determine the trophic status of the whole water column. The intensity of the allochthonous input in a coastal environment subjected to strong anthropogenic pressures determines an increase in the benthic oxygen demand leading to depressed oxygen levels in the bottom waters. Anoxic conditions resulting from organic enrichment can enhance the exchange of nutrients between sediments and the overlying water. In the present study, carbon and nutrient fluxes at the sediment-water interface were measured at two experimental sites, one highly and one moderately contaminated, as reference point. In situ benthic flux measurements of dissolved species (O2, DIC, DOC, N-NO3 -, N-NO2 -, N-NH4 +, P-PO4 3-, Si-Si(OH)4, H2S) were conducted using benthic chambers. Furthermore, undisturbed sediment cores were collected for analyses of total and organic C, total N, and biopolymeric carbon (carbohydrates, proteins, and lipids) as well as of dissolved species in porewaters and supernatant in order to calculate the diffusive fluxes. The sediments were characterized by suboxic to anoxic conditions with redox values more negative in the highly contaminated site, which was also characterized by higher biopolymeric carbon content (most of all lipids), lower C/N ratios and generally higher diffusive fluxes, which could result in a higher release of contaminants. A great difference was observed between diffusive and in situ benthic fluxes suggesting the enhancing of fluxes by bioturbation and the occurrence of biogeochemically important processes at the sediment-water interface. The multi-contamination of both inorganic and organic pollutants, in the sediments of the Mar Piccolo of Taranto (declared SIN in 1998), potentially transferable to the water column and to the aquatic trophic chain, is of serious concern for its ecological relevance, also considering the widespread fishing and mussel farming activities in the area

(39) Zhang J, Wu H, Zhao Y, Zu H. Therapeutic Effects of Hydrogen Sulfide in Treating Delayed Encephalopathy After Acute Carbon Monoxide Poisoning. Am J Ther 2015 Jul 8. Abstract: Carbon monoxide (CO) poisoning is one of the most common diseases induced by CO injury. More than a half of the survivors still likely to have cognitive dysfunction, which is delayed encephalopathy after acute CO poisoning. There is no other effective treatment for delayed encephalopathy after acute CO poisoning except hyperbaric oxygen. Hydrogen sulfide is a novel signal molecule for the central nervous system regulation and plays a role of neural protection in many diseases. H2S has the inhibitory effects on oxidative stress and apoptosis to protect against oxidative damage of nerve. A CO-poisoning rat model was established to detect the effect of H2S on delayed encephalopathy after acute CO poisoning. Spatial learning and memory was tested by Morris water maze. Nissl staining and terminal deoxynucleotidyl transferase-mediated nick end labeling assay were used to examine apoptosis induced by CO poisoning in the brain. Then, the protein levels of proinflammatory cytokines and the indicators of oxidative damage were measured. We found that H2S significantly improved cognitive function, reduced apoptosis and the inflammatory response, and decreased the oxidative damage

16

induced by CO poisoning in rats. These results suggest that H2S may be a novel specific and effective treatment of delayed encephalopathy of CO poisoning

(40) Xin H, Wang M, Tang W, Shen Z, Miao L, Wu W, et al. Hydrogen sulfide attenuates inflammatory hepcidin by reducing IL-6 secretion and promoting SIRT1-mediated STAT3 deacetylation. Antioxid Redox Signal 2015 Jul 8. Abstract: <b><i>Aims:</b></i> Anemia of inflammation is quite prevalent in hospitalized patients with poor prognosis. Concerns about the effectiveness and safety of iron supplementation have arisen, driving the demand for alternative therapies. Induction of hepatic hepcidin, the master hormone of iron homeostasis, causes anemia under inflammatory conditions. Previous studies indicated that hydrogen sulfide (H₂S), the third gasotransmitter and a well-known regulator of inflammation, may inhibit the secretion of inflammatory cytokines. We thus investigated the effect of H₂S on inflammatory hepcidin induction. <b><i>Results:</b></i> H₂S suppressed lipopolysaccharide (LPS)-induced hepcidin production and regulated iron homeostasis in mice by decreasing serum interleukin-6 (IL-6) and Janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) activation; similar results were obtained in Huh7 cells exposed to conditioned medium from LPS-challenged THP-1 macrophages. Intriguingly, we found H₂S also attenuated hepcidin levels in Huh7 cells and mouse primary hepatocytes in a SIRT1-dependent manner. By promoting SIRT1 expression and stabilizing SIRT1-STAT3 interactions, H₂S ameliorated IL-6-induced STAT3 acetylation, resulting in reduced hepcidin production. Inhibition and silencing of SIRT1 diminished H₂S-mediated suppression of hepcidin, as opposed to SIRT1 activation and overexpression. Consistent results were observed <i>in vivo</i>. Furthermore, knockout of cystathionine gamma-lyase (CSE), an endogenous H₂S synthase, exaggerated inflammatory hepcidin expression in mice. <b><i>Innovation:</b></i> For the first time we elucidated the effects and possible mechanisms of H₂S on inflammatory hepcidin, and established a novel regulatory link between SIRT1 and hepcidin. <b><i>Conclusion:</b></i> Our work demonstrates that H₂S attenuates inflammation-induced hepatic hepcidin via multi-pathways, and suggests new treatment strategies for anemia of inflammation

(41) Jiang H, Xiao J, Kang B, Zhu X, Xin N, Wang Z. PI3K/SGK1/GSK3beta signaling pathway Is involved in inhibition of autophagy in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation by Hydrogen sulfide. Exp Cell Res 2015 Jul 8. Abstract: Excessive autophagy aggravates myocardial ischemia/reperfusion (IR) injury. Hydrogen sulfide (H2S) has been shown to possess a strong cardioprotective effect due to its anti-necrosis, anti-apoptosis, anti-oxidant and anti-inflammatory properties. Our previous study showed that H2S could also protect the myocardium against IR injury through its anti-autophagy effect in vivo, but the underlying mechanism remains unclear. The aim of the present study was to determine whether PI3K/SGK1/GSK3beta signaling pathway was involved in the anti-autophagy effect of H2S against myocardial hypoxia/reoxygenation (HR) injury in vitro. Autophagy was significantly increased in cardiomyocytes subjected to HR, but it was down-regulated by H2S (NaHS donor). Blocking PI3K by LY294002 (a PI3K inhibitor) or knocking down SGK1 by SGK1 siRNA augmented autophagy and attenuated the anti-autophagy effect of H2S. However, blocking GSK3beta by tws119 (a GSK3beta inhibitor) produced an opposite effect. In addition, while treatment of neonatal rat cardiomyocytes with HR reduced cell viability and augmented cell injury, H2S significantly reversed it. Blocking PI3K or knocking down SGK1 aggravated HR injury and weakened the protective effect of H2S, while blocking GSK3beta produced an opposite effect. In conclusion, H2S can inhibit autophagy in neonatal rat cardiomyocytes exposed to H/R and exert a cardioprotective effect at least partly by regulating PI3K/SGK1/GSK3beta signaling pathway

17

(42) Li L, Jiang HK, Li YP, Guo YP. Hydrogen sulfide protects spinal cord and induces autophagy via miR-30c in a rat model of spinal cord ischemia-reperfusion injury. J Biomed Sci 2015;22(1):50. Abstract: BACKGROUND: Hydrogen sulfide (H2S), a novel gaseous mediator, has been recognized as an important neuromodulator and neuroprotective agent in the nervous system. The present study was undertaken to study the effects of exogenous H2S on ischemia/reperfusion (I/R) injury of spinal cord and the underlying mechanisms. METHODS: The effects of exogenous H2S on I/R injury were examined by using assessment of hind motor function, spinal cord infarct zone by Triphenyltetrazolium chloride (TTC) staining. Autophagy was evaluated by expressions of Microtubule associated protein 1 light chain 3 (LC3) and Beclin-1 which were determined by using Quantitative Real-Time PCR and Western blotting, respectively. RESULTS: Compared to I/R injury groups, H2S pretreatment had reduced spinal cord infarct zone, improved hind motor function in rats. Quantitative Real-Time PCR or Western blotting results showed that H2S pretreatment also downregulated miR-30c expression and upregulated Beclin-1 and LC3II expression in spinal cord. In vitro, miR-30c was showed to exert negative effect on Beclin-1 expression by targeting its 3'UTR in SY-SH-5Y cells treated with Oxygen, Glucose Deprivation (OGD). In rat model of I/R injury, pretreatment of pre-miR-30c or 3-MA (an inhibitor for autophagy) can abrogated spinal cord protective effect of H2S. CONCLUSION: H2S protects spinal cord and induces autophagy via miR-30c in a rat model of spinal cord hemia-reperfusion injury

(43) Wei X, Zhang B, Zhang Y, Li H, Cheng L, Zhao X, et al. Hydrogen Sulfide Inhalation Improves Neurological Outcome via NF-kappaB-Mediated Inflammatory Pathway in a Rat Model of Cardiac Arrest and Resuscitation. Cell Physiol Biochem 2015 Jul 6;36(4):1527-38. Abstract: BACKGROUND/AIMS: The effects of H2S on cerebral inflammatory reaction after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) remain poorly understood. In this study, we investigated the effects of exogenous 40 ppm and 80 ppm H2S gas on inflammatory reaction and neurological outcome after CA/CPR. METHODS: CA was induced by ventricular fibrillation and followed by CPR. Forty or 80 ppm H2S was inhaled for 1 h immediately following CPR. The levels of IL-1beta, IL-6 and TNF-alpha, the myeloperoxidase (MPO) activity, the expression of iNOS and ICAM-1, and the phosphorylation and translocation of NF-kappaB were evaluated at 24 h after CA/CPR. The tape removal test, survival rate and hippocampal neuronal counts were investigated at 14 d after CA/CPR. RESULTS: CA/CPR induced significant increases in IL-1beta, IL-6, TNF-alpha and MPO activity. The phosphorylation and translocation of NF-kappaB, and the expression of iNOS and ICAM-1 were increased significantly. Inhalation of 40 or 80 ppm H2S gas decreased these inflammatory cytokines. Furthermore, 40 or 80 ppm H2S inhibited the activation of NF-kappaB and the downstream proinflammatory mediators iNOS and ICAM-1. H2S inhalation also improved neurological function, 14-d survival rate, and reduced hippocampal neuronal loss. CONCLUSION: These results indicated that inhalation of H2S protected against brain injury after CA/CPR. The mechanisms underlying protective effects of H2S were associated with the inhibition of CA/CPR-induced inflammation reactions by reducing IL-1beta, IL-6 and TNF-alpha, and concomitantly inhibiting the activation and infiltration of neutrophils. The beneficial effects of H2S might be mediated by downregulation of NF-kappaB and the downstream proinflammatory signaling pathway. (c) 2015 S. Karger AG, Basel

(44) Di CA, Pezzuto F, Canello S, Guidetti G, Palmieri B. Therapeutic Effectiveness of a Dietary Supplement for Management of Halitosis in Dogs. J Vis Exp 2015;(101). Abstract: Halitosis is a common complaint involving social and communicational problems in humans and also affects the pet-owner relationship. In this randomized placebo-controlled crossover clinical evaluation, we assessed the effectiveness of a dedicated dietary supplement to improve chronic halitosis in 32 dogs of different breeds and ages. This protocol describes how to evalute the presence of oral volatile suphur compunds, e.g. methyl mercaptan, hydrogen sulfide and dimethyl sulfide, by means of a

18

portable gas chromatograph device coupled with a syringe, which was used to collect the breath, and a dedicated software, which allows the operator to monitor each compound concentration during each measurement, in a relatively short time (8 min). A significant modification of halitosis parameters was observed after 30 days since the beginning of treatment (p <0.05), while a long-lasting effect was still observed even 20 days after the suspension of the treatment. Portable gas chromatograph, which is also widely used in clinical practice, can be therefore used to confirm and control halitosis in humans and animals. Even though human and animal species present some differences, this innovative and alternative therapy for halitosis management might be extended to human clinical practice as an adjuvant dietary approach

(45) Azizi F, Seifi B, Kadkhodaee M, Ahghari P. Administration of hydrogen sulfide protects ischemia reperfusion-induced acute kidney injury by reducing the oxidative stress. Ir J Med Sci 2015 Jul 4. Abstract: BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury. Hydrogen sulfide (H2S) has been known as a novel gaseous signaling molecule. AIMS: The aim of this study was to investigate whether the efficacy of H2S in protecting against renal IRI is through its antioxidative effect. METHOD: In this study, rats were randomized into Sham, IR, or sodium hydrosulfide (NaHS, an H2S donor) groups. To establish a model of renal IRI, both renal arteries were occluded for 55 min and then declamped to allow reperfusion for 24 h. Rats in the NaHS group received intraperitoneal injections of 75 mumol/kg NaHS 10 min before the onset of ischemia and immediately after the onset of reperfusion. Sham group underwent laparotomy without cross-clamping of renal pedicles. After reperfusion, plasma and renal tissue samples were collected for functional, histological, and oxidative stress evaluation. RESULTS: The IR group exhibited significant rise in plasma creatinine, blood urea nitrogen (BUN), renal malondialdehyde (MDA) concentration, and significant reduction of renal superoxide dismutase (SOD) activity. Treatment with NaHS reduced the levels of plasma creatinine, BUN, renal MDA concentration, and increased SOD activity in the kidneys. NaHS improved renal histological changes in comparison to IR group. CONCLUSION: Our data demonstrated that H2S can protect against renal IRI and that its therapeutic effects may be mediated by reducing oxidative stress

(46) Li Z, Huang Y, Zhang S, Chen W, Kuang Z, Ao D, et al. A fast response & recovery HS gas sensor based on alpha-FeO nanoparticles with ppb level detection limit. J Hazard Mater 2015 Jul 3;300:167-74. Abstract: H2S gas sensor based on alpha-Fe2O3 nanoparticles was fabricated by post-thermal annealing of Fe3O4 precursor which was synthesized using a facile hydrothermal route. The characteristic techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were adopted to characterize the chemical composition and microstructure of the obtained samples. Gas-sensing performance of the sensor was investigated at different operation temperatures from 100 degrees C to 400 degrees C. Results showed that the sensor exhibited the best sensitivity, reproducibility and long-term stability for detecting H2S gas at an operating temperature of 300 degrees C. The detection limit towards H2S gas was 0.05ppm, and the response time and recovery time was 30s and 5s, respectively. In addition, sensing mechanism of the sensor towards H2S was discussed

(47) Han SJ, Kim JI, Park JW, Park KM. Hydrogen sulfide accelerates the recovery of kidney tubules after renal ischemia/reperfusion injury. Nephrol Dial Transplant 2015 Jul 3. Abstract: BACKGROUND: Progression of acute kidney injury to chronic kidney disease (CKD) is associated with inadequate recovery of damaged kidney. Hydrogen sulfide (H2S) regulates a variety of cellular signals involved in cell death, differentiation and proliferation. This study aimed to identify the role of H2S and its producing enzymes in the recovery of kidney following ischemia/reperfusion (I/R) injury. METHODS: Mice were subjected to 30 min of bilateral renal ischemia. Some mice were administered daily NaHS, an H2S donor,

19

and propargylglycine (PAG), an inhibitor of the H2S-producing enzyme cystathionine gamma-lyase (CSE), during the recovery phase. Cell proliferation was assessed via 5'-bromo-2'-deoxyuridine (BrdU) incorporation assay. RESULTS: Ischemia resulted in decreases in CSE and cystathionine beta-synthase (CBS) expression and activity, and H2S level in the kidney. These decreases did not return to sham level until 8 days after ischemia when kidney had fibrotic lesions. NaHS administration to I/R-injured mice accelerated the recovery of renal function and tubule morphology, whereas PAG delayed that. Furthermore, PAG increased mortality after ischemia. NaHS administration to I/R-injured mice accelerated tubular cell proliferation, whereas it inhibited interstitial cell proliferation. In addition, NaHS treatment reduced post-I/R superoxide formation, lipid peroxidation, level of GSSG/GSH and Nox4 expression, whereas it increased catalase and MnSOD expression. CONCLUSIONS: Our findings demonstrate that H2S accelerates the recovery of I/R-induced kidney damage, suggesting that the H2S-producing transsulfuration pathway plays an important role in kidney repair after acute injury

(48) Wild V, Messlinger K, Fischer MJ. Hydrogen sulfide determines HNO-induced stimulation of trigeminal afferents. Neurosci Lett 2015 Jul 3;602:104-9. Abstract: Endogenous NO and hydrogen sulfide form HNO, which causes CGRP release via TRPA1 channel activation in sensory nerves. In the present study, stimulation of intact trigeminal afferent neuron preparations with NO donors, Na2S or both was analyzed by measuring CGRP release as an index of mass activation. Combined stimulation was able to activate all parts of the trigeminal system and acted synergistic compared to stimulation with both substances alone. To investigate the contribution of both substances, we varied their ratio and tracked intracellular calcium in isolated neurons. Our results demonstrate that hydrogen sulfide is the rate-limiting factor for HNO formation. CGRP has a key role in migraine pathophysiology and HNO formation at all sites of the trigeminal system should be considered for this novel means of activation

(49) Liu MH, Zhang Y, Lin XL, He J, Tan TP, Wu SJ, et al. Hydrogen sulfide attenuates doxorubicininduced cardiotoxicity by inhibiting calreticulin expression in H9c2 cells. Mol Med Rep 2015 Jul 2. Abstract: Doxorubicin (DOX) is a potent and currently available antitumor therapeutic agent; however, its clinical application is limited by the occurrence of cardiotoxicity. Preliminary evidence indicates that hydrogen sulfide (H2S) may exert protective effects against DOX cardiotoxicity. Therefore, the aim of the present study was to investigate whether calreticulin (CRT) is involved in the cardioprotection of H2S against DOXinduced cardiotoxicity. DOX was observed to markedly induce injuries, including cytotoxicity and apoptosis, and also enhance the expression level of CRT. Notably, pretreatment of H9c2 cells with sodium hydrosulfide (a donor of H2S) significantly attenuated the decreased cell viability, the increased apoptosis rate and the increased expression level of CRT in H9c2 cells. In addition, pretreatment of H9c2 cells with NacetylLcysteine, a scavenger of reactive oxygen species (ROS) prior to exposure to DOX, markedly decreased the expression of CRT. These results indicate that exogenous H2S attenuates DOXinduced cardiotoxicity by inhibiting CRT expression in H9c2 cardiac cells

(50) Han ZH, Jiang YI, Duan YY, Wang XY, Huang Y, Fang TZ. Protective effects of hydrogen sulfide inhalation on oxidative stress in rats with cotton smoke inhalation-induced lung injury. Exp Ther Med 2015 Jul;10(1):164-8. Abstract: The aim of the present study was to investigate the mechanism by which hydrogen sulfide (H2S) inhalation protects against oxidative stress in rats with cotton smoke inhalation-induced lung injury. A total of 24 male Sprague-Dawley rats were separated randomly into four groups, which included the control, H2S, smoke and smoke + H2S groups. A rat model of cotton smoke inhalation-induced lung injury was established following inhalation of 30% oxygen for 6 h. In addition, H2S (80 ppm) was inhaled by the rats in the H2S and smoke + H2S groups for 6 h following smoke or sham-smoke inhalation. Enzyme-linked immunosorbent assays were performed to measure various indices in the

20

rat lung homogenate, while the levels of nuclear factor (NF)-kappaBp65 in the lung tissue of the rats were determined and semiquantitatively analyzed using immunohistochemistry. In addition, quantitative fluorescence polymerase chain reaction was employed to detect the mRNA expression of inducible nitric oxide synthase (iNOS) in the rat lung tissue. The concentrations of malondialdehyde (MDA), nitric oxide (NO), inducible iNOS and NF-kappaBp65, as well as the sum-integrated optical density of NF-kappaBp65 and the relative mRNA expression of iNOS, in the rat lung tissue from the smoke + H2S group were significantly lower when compared with the smoke group. The concentrations of MDA, NO, iNOS and NF-kappaBp65 in the H2S group were comparable to that of the control group. Therefore, inhalation of 80 ppm H2S may reduce iNOS mRNA transcription and the production of iNOS and NO in rats by inhibiting NF-kappaBp65 activation, subsequently decreasing oxidative stress and cotton smoke inhalation-induced lung injury

(51) Lee EH, Moon KE, Kim TG, Lee SD, Cho KS. Inhibitory effects of sulfur compounds on methane oxidation by a methane-oxidizing consortium. J Biosci Bioeng 2015 Jul 1. Abstract: Kinetic and enzymatic inhibition experiments were performed to investigate the effects of methanethiol (MT) and hydrogen sulfide (H2S) on methane oxidation by a methane-oxidizing consortium. In the coexistence of MT and H2S, the oxidation of methane was delayed until MT and H2S were completely degraded. MT and H2S could be degraded, both with and without methane. The kinetic analysis revealed that the methane-oxidizing consortium showed a maximum methane oxidation rate (Vmax) of 3.7 mmol g-dry cell weight (DCW)-1 h-1 and a saturation constant (Km) of 184.1 muM. MT and H2S show competitive inhibition on methane oxidation, with inhibition values (Ki) of 1504.8 and 359.8 muM, respectively. MT was primary removed by particulate methane monooxygenases (pMMO) of the consortium, while H2S was degraded by the other microorganisms or enzymes in the consortium. DNA and mRNA transcript levels of the pmoA gene expressions were decreased to approximately 106 and 103pmoA gene copy number g-DCW-1 after MT and H2S degradation, respectively; however, both the amount of the DNA and mRNA transcript recovered their initial levels of approximately 107 and 105pmoA gene copy number g-DCW-1 after methane oxidation, respectively. The gene expression results indicate that the pmoA gene could be rapidly reproducible after methane oxidation. This study provides comprehensive information of kinetic interactions between methane and sulfur compounds

(52) Daigger GT, Hodgkinson A, Aquilina S, Fries MK. Development and Implementation of a Novel Sulfur Removal Process from H2S Containing Wastewaters. Water Environ Res 2015 Jul;87(7):618-25. Abstract: A novel process for removing sulfur from wastewater containing dissolved sulfide has been developed and implemented in a membrane bioreactor (MBR) process treating anaerobically pretreated industrial (pulp and paper) wastewater at the Gippsland Water Factory. Controlled oxygen addition to the first bioreactor zone (constituting 27.7% of the total bioreactor volume) to create oxygen-limiting conditions, followed by oxygen-sufficient conditions in the remaining zones of the bioreactor, provide the necessary conditions. Dissolved sulfide is oxidized to elemental sulfur in the first zone, and the accumulated sulfur is retained in the bioreactor mixed liquor suspended solids (MLSS) in the remaining zones. Accumulated sulfur is removed from the process in the waste activated sludge (WAS). Oxidation of dissolved sulfide to elemental sulfur reduces the associated process oxygen requirement by 75% compared to oxidation to sulfate. Microscopic examinations confirm that biological accumulation of elemental sulfur occurs. Process performance was analyzed during a nearly 2-year commissioning and optimization period. Addition of air in proportion to the process influent dissolved sulfide loading proved the most effective process control approach, followed by the maintenance of dissolved oxygen concentrations of 1.0 and 1.5 mg/L in the two downstream bioreactor zones. Sufficient oxygen is added for the stoichiometric conversion of dissolved sulfide to elemental sulfur. Enhanced biological phosphorus removal also occurred under these conditions, thereby simplifying

21

supplemental phosphorus addition. These operating conditions also appear to lead to low and stable capillary suction time values for the MBR mixed liquor

(53) Yoo KS, Han SD, Moon HG, Yoon SJ, Kang CY. Highly Sensitive H2S Sensor Based on the Metal-Catalyzed SnO2 Nanocolumns Fabricated by Glancing Angle Deposition. Sensors (Basel) 2015;15(7):15468-77. Abstract: As highly sensitive H2S gas sensors, Au- and Ag-catalyzed SnO2 thin films with morphology-controlled nanostructures were fabricated by using e-beam evaporation in combination with the glancing angle deposition (GAD) technique. After annealing at 500 degrees C for 40 h, the sensors showed a polycrystalline phase with a porous, tilted columnar nanostructure. The gas sensitivities (S = Rgas/Rair) of Au and Ag-catalyzed SnO2 sensors fabricated by the GAD process were 0.009 and 0.015, respectively, under 5 ppm H2S at 300 degrees C, and the 90% response time was approximately 5 s. These sensors showed excellent sensitivities compared with the SnO2 thin film sensors that were deposited normally (glancing angle = 0 degrees , S = 0.48)

(54) Lauricella M, Meloni S, Liang S, English NJ, Kusalik PG, Ciccotti G. Clathrate structure-type recognition: Application to hydrate nucleation and crystallisation. J Chem Phys 2015 Jun 28;142(24):244503. Abstract: For clathrate-hydrate polymorphic structure-type (sI versus sII), geometric recognition criteria have been developed and validated. These are applied to the study of the rich interplay and development of both sI and sII motifs in a variety of hydrate-nucleation events for methane and H2S hydrate studied by direct and enhanced-sampling molecular dynamics (MD) simulations. In the case of nucleation of methane hydrate from enhanced-sampling simulation, we notice that already at the transition state, approximately 80% of the enclathrated CH4 molecules are contained in a well-structured (sII) clathrate-like crystallite. For direct MD simulation of nucleation of H2S hydrate, some sI/sII polymorphic diversity was encountered, and it was found that a realistic dissipation of the nucleation energy (in view of non-equilibrium relaxation to either microcanonical (NVE) or isothermal-isobaric (NPT) distributions) is important to determine the relative propensity to form sI versus sII motifs

(55) Wang XB, Du JB, Cui H. Signal pathways involved in the biological effects of sulfur dioxide. Eur J Pharmacol 2015 Jun 27;764:94-9. Abstract: Gasotransmitters, such as nitric oxide, carbon monoxide and hydrogen sulfide, play important roles in life and have attracted great interest in scientists. In recent years, sulfur dioxide (SO2) has also been found to play important roles in mammals. The redox pathway is involved in the biological effects of SO2, such as the protective effect on myocardial ischemia reperfusion, myocardial injury, pulmonary hypertension and atherosclerosis. Ion channels, such as L-type calcium and adenosine triphosphate-sensitive potassium channels, as well as 3'-5'-cyclic guanosine monophosphate and 3'-5'-cyclic adenosine monophosphate pathways are also involved in the vasorelaxant effect of SO2. The mitogen-activated protein kinase pathway plays roles in vascular remodeling during pulmonary hypertension and vascular smooth muscle cell proliferation. Understanding these signaling mechanisms would help to clarify the pathophysiological effect and therapeutic potential of SO2

(56) Perry SF, Tzaneva V. The sensing of respiratory gases in fish: Mechanisms and signalling pathways Mechanisms of chemoreception in fish. Respir Physiol Neurobiol 2015 Jun 27. Abstract: Chemoreception in fish is critical for sensing changes in the chemical composition of the external and internal environments and is often the first step in a cascade of events leading to cardiorespiratory and metabolic adjustments. Of paramount importance is the ability to sense changes in the levels of the three respiratory gases, oxygen (O2), carbon dioxide (CO2) and ammonia (NH3). In this review, we discuss the role of piscine neuroepithelial cells (NEC), putative peripheral chemoreceptors, as tri-modal sensors of O2, CO2 and NH3. Where possible, we elaborate on the signalling pathways linking NEC

22

stimulation to afferent responses, the potential role of neurotransmitters in activating downstream neuronal pathways and the impact of altered levels of the respiratory gases on NEC structure and function. Although serotonin, the major neurotransmitter contained within NECs, is presumed to be the principal agent eliciting the reflex responses to altered levels of the respiratory gases, there is accumulating evidence for the involvement of "gasomitters", a class of gaseous neurotransmitters which includes nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H2S). Recent data suggest that CO inhibits and H2S stimulates NEC activity whereas NO can either be inhibitory or stimulatory depending on developmental age

(57) Asakura H. Sulfate and organic matter concentration in relation to hydrogen sulfide generation at inert solid waste landfill site - Limit value for gypsum. Waste Manag 2015 Jun 26. Abstract: In order to suggest a limit value for gypsum (CaSO4) for the suppression of hydrogen sulfide (H2S) generation at an inert solid waste landfill site, the relationship between raw material (SO4 and organic matter) for H2S generation and generated H2S concentration, and the balance of raw material (SO4) and product (H2S) considering generation and outflow were investigated. SO4 concentration should be less than approximately 100mg-SO4/L in order to suppress H2S generation to below 2000ppm. Total organic carbon (TOC) concentration should be less than approximately 200mg-C/L assuming a high SO4 concentration. The limit value for SO4 in the ground is 60mg-SO4/kg with 0.011wt% as gypsum dihydrate, i.e., approximately 1/10 of the limit value in inert waste as defined by the EU Council Decision (560mg-SO4/kg-waste). The limit value for SO4 in inert waste as defined by the EU Council Decision is high and TOC is strictly excluded. The cumulative amount of SO4 outflow through the liquid phase is much larger than that through the gas phase. SO4 concentration in pore water decreases with time, reaching half the initial concentration around day 100. SO4 reduction by rainfall can be expected in the long term

(58) Li XJ, Li CK, Wei LY, Lu N, Wang GH, Zhao HG, et al. Hydrogen sulfide intervention in focal cerebral ischemia/reperfusion injury in rats. Neural Regen Res 2015 Jun;10(6):932-7. Abstract: The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors

(59) Vaitheeswari S, Sriram R, Brindha P, Kurian GA. Studying inhibition of calcium oxalate stone formation: an in vitro approach for screening hydrogen sulfide and its metabolites. Int Braz J Urol 2015 May;41(3):503-10. Abstract: PURPOSE: Calcium oxalate urolithiasis is one of the most common urinary tract diseases and is of high prevalence. The present study proposes to evaluate the antilithiatic property of hydrogen sulfide and its metabolites like thiosulfate & sulfate in an in vitro model. MATERIALS AND METHODS: The antilithiatic activity of sodium hydrogen sulfide (NaSH), sodium thiosulfate (Na2S2O3) and sodium sulfate (Na2SO4) on the kinetics of calcium oxalate crystal formation was investigated both in physiological buffer and in urine from normal and recurrent stone forming volunteers. The stones were characterized by optical and spectroscopic techniques. RESULTS: The stones were characterized to be monoclinic, prismatic and bipyramidal habit which is of calcium monohydrate and dihydrate nature. The FTIR displayed fingerprint corresponding to calcium oxalate in the control while in NaSH

23

treated, S=O vibrations were visible in the spectrum. The order of percentage inhibition was NaSH>Na2S2O3>Na2SO4. CONCLUSION: Our study indicates that sodium hydrogen sulfide and its metabolite thiosulfate are inhibitors of calcium oxalate stone agglomeration which makes them unstable both in physiological buffer and in urine. This effect is attributed to pH changes and complexing of calcium by S2O3 (2)-and SO4 (2)- moiety produced by the test compounds

(60) Tran BH, Huang C, Zhang Q, Liu X, Lin S, Liu H, et al. Cardioprotective effects and pharmacokinetic properties of a controlled release formulation of a novel hydrogen sulfide donor in rats with acute myocardial infarction. Biosci Rep 2015;35(3). Abstract: We previously reported that S-propargyl-cysteine (SPRC) exerts cardioprotective effects by elevating H2S levels via the CSE/H2S pathway. In the present study, we investigated the cardioprotective effects and pharmacokinetic properties of a controlled release formulation of SPRC (CR-SPRC) in an in vivo rat model of myocardial infarction (MI). Rats were randomly assigned to seven groups that were pre-treated with CR-SPRC daily for 7 days prior to ligation of the left anterior descending coronary artery to induce MI. Cardiac function and infarct size were determined after MI, and we examined the activity of antioxidant enzymes, expression of anti-inflammation proteins and hydrogen sulfide levels. Mixed-mode, reversed-phase and cation-exchange HPLC-MS/MS were used to compare the pharmacokinetic properties of CR-SPRC and SPRC. CR-SPRC significantly reduced infarct size and creatine kinase (CK) and lactate dehydrogenase (LDH) leakage and it preserved cardiac function during MI. CR-SPRC displayed antioxidant properties, preserving glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) levels whereas reducing malondialdehyde (MDA) levels. Moreover, CR-SPRC significantly reduced the protein levels of inflammatory biomarkers (phospho-NF-kappaB p65/NF-kappaB p65, TNF-alpha) and increased cystathionine-gamma-lyase (CSE) and Ikappa-Balpha protein levels. CR-SPRC had better pharmacokinetic properties than SPRC, with a reduced concentration peak (Cmax), prolonged time to reach peak concentration (Tmax), prolonged mean residence time (MRTinf) and increased AUC0-t. CR-SPRC showed protective effects against MI via the CSE/H2S pathway and demonstrated better cardioprotective effects than SPRC by prolonging the release of endogenous H2S

(61) Shiyao L, Yamei X, Deyu H. [Anti-halitosis effect of sugar-free chewing gum]. Hua Xi Kou Qiang Yi Xue Za Zhi 2015 Apr;33(2):166-8. Abstract: OBJECTIVE: To study the anti-halitosis effect of sugar-free chewing gum through their influence on odor induced by cysteine. METHODS: Ten volunteers were randomly divided into the treatment group and the untreated group; each group consisted of five volunteers. All volunteers consented to participate in a test in which breath odor was induced by cysteine. After the test, the treatment group chewed sugar-free chewing gum for 1 min, whereas the untreated group did not undergo any treatment. The effectiveness was determined by the percent reduction of H2S, CH3SH, and (CH3)2S response after the volunteers chewed gum for 1, 10, and 20 min. RESULTS: At 1, 10, and 20 min, H2S of the treatment group was reduced by 82.68%, 92.27%, 97.47%, respectively, CH3SH was reduced by 65.49%, 73.79%, and 82.89%, respectively, and (CH3)2S was reduced by 60.45%, 73.82%, and 59.72%, respectively. The differences between the two groups at different times were significant (P < 0.05). CONCLUSION: Chewing gum can effectively inhibit cysteine-induced odor

(62) Wang B, Xu X, Liang G, Zhang Y, Liu L, Zhang J. [Correlative study of the metabolic disorder of hippocampus and cerebral cortex and cognitive impairment in moderate to severe OSAHS patients]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2015 Apr;29(7):607-11. Abstract: OBJECTIVE: To research the serum levels of BDNF, H2S and S-100beta as metabolic product of hippocampus and cerebral cortex in moderate to severe obstructive sleep apnea hypopnea syndrome(OSAHS) patients before and after surgery, and to analyze their correlations with cognitive impairment. METHOD: Forty-four randomly

24

selected diagnosed OSAHS patients were divided into two groups according to Montreal Cognitive Assessment (MoCA), 19 cases in cognitively normal group and 25 cases in cognitive dysfunction group. Cases in cognitive dysfunction group underwent UPPP oriented surgery, and received 6 months follow-up, 21 cases were remained as treament group, 4 cases lost. 19 cases of healthy subjects were randomly selected as the normal control group. All groups were detected for the serum BDNF, H2S and S-100beta levels to analyze the correlations between the biochemical indexes and sleep disorders indexes, hypoxia levels and cognitive function scores. RESULT: (1) In the comparison between the treatment group and the normal control group regarding PSG monitoring results, the AHI, I + II, LA/HT and SLT90% indexes of OSAHS patients increased, and the III + IV phase, REM phase, MSaO2 and LSaO2 decreased. In the comparison between the cognitive dysfunction group and the cognitively normal group, the III + IV, REM and LSaO2 indexes of the cognitive dysfunction group decreased. (2) In the comparison between cognitive dysfunction group and cognitively normal group, and between the treatment group and the normal control group, BDNF and H2S levels increased and S-100beta levels decreased, and the MoCA total scores, attention, memory/delayed recall scores decreased. (3) The correlation between biochemical indexes with PSG indexes was as follows. The serum BNDF and H2S levels were negatively correlated with AHI index. The serum BNDF and H2S levels were positively correlated with III + IV stage, REM stage and MSaO2 indexes. The S-100beta level was positively correlated with AHI index, and S-100beta levels were negatively correlated with III + IV stage, REM stage, MSaO2 and LSaO2 indexes. (4) The correlation between biochemical indexes and MoCA scores was as follows. The serum BNDF and H2S levels were positively correlated with MoCA total scores, attention, and memory/delayed recall scores. The serum S-100beta levels were negatively correlated with MoCA total scores, attention and memory/ delayed recall scores. (5) The linear regression equation between MoCA total scores in cognitive dysfunction group of OSAHS patients and the serum BNDF, H2S and S-100beta levels was as follows: Y(MoCA) = 40.131 + 0.22 X(BDNF) + 0.012 X(H2S)-0.647X(S-100beta) (R2 = 0.461). CONCLUSION: OSAHS patients with sleep disorder and nocturnal hypoxemia might suffer from cognitive dysfunction in which attention and memory predominates. Serum BNDF, H2S and S-100beta levels, which could indirectly reflect the metabolic abnormalities degree of hippocampus and cerebral cortex, are sensitive indicators of early cognitive dysfunction in OSAHS patients

(63) Lu K. [Determination of total cyanides and sulfides in wastewater using ion chromatography coupled with ultraviolet photo-dissociation/gas-membrane diffusion]. Se Pu 2015 Mar;33(3):298-303. Abstract: An automated system for the determination of total cyanides and sulfides in wastewater has been developed using flow injection, ultraviolet (UV) photo-dissociation, gas-membrane diffusion, column trapping, ion chromatography separation and pulsed amperometric detection. When the sample was mixed with sulfuric acid and hypophosphorous acid medium containing the appropriate amount of sulfamic acid, ascorbic acid, EDTA and citric acid, metal-cyanide complexes such as Fe (CN)3-(6) can be photo-dissociated by 312 nm UV light, which results in hydrogen cyanide ( HCN) and similarly, sulfides release hydrogen sulfide (H2S). These products were diffused through a 0.45 microm hydrophobic porous polypropylene membrane and were then absorbed in the dilute NaOH solution, concentrated with a Metrosep A PCC 1 HC/4.0 column, separated on an IonPac AS7 column, and finally detected by the pulsed amperometric detector with Ag electrode. The total cyanides and sulfides were good linear in the range of 0.5-1,000 microg/L with correlation coefficients of 0.998 9 and 0.999 7 respectively. The recoveries were 93%-102% and the limits of detection were 0.5 microg/L for total cyanides and 1.0 microg/L for sulfides under the conditions of the sample volume of 100 microL and the signal to noise ratio of 5. The sample throughput of the system was six samples per hour. The results from this new method have been compared with the ones obtained with the standard method, which shows a good agreement

25

(64) Liu H, Deng Y, Gao J, Liu Y, Li W, Shi J, et al. Sodium Hydrosulfide Attenuates Beta-Amyloid-Induced Cognitive Deficits and Neuroinflammation via Modulation of MAPK/NF-kappaB Pathway in Rats. Curr Alzheimer Res 2015;12(7):673-83. Abstract: Beta-amyloid (Abeta), a neurotoxic peptide, accumulates in the brain of Alzheimer's disease (AD) subjects to initiate neuroinflammation eventually leading to memory impairment. Here, we demonstrated that Abeta-injected rats exhibited cognitive impairment and neuroinflammation with a remarkable reduction of hydrogen sulfide (H2S) levels in the hippocampus compared with that in shamoperated rats. Interestingly, the expression of cystathionine-beta-synthase (CBS) and 3- mercaptopyruvate-sulfurtransferase (3MST), the major enzymes responsible for endogenous H2S generation, were also significantly decreased. However, intraperitoneal (i.p.) injection of sodium hydrosulfide (NaHS, a H2S donor) dramatically attenuated cognitive impairment and neuroinflammation induced by hippocampal injection of 10 mug of Abeta1-42 in rats. Subsequently, NaHS significantly suppressed the expression of tumor necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta) and cyclooxygenase-2 (COX-2) in rat hippocampus following Abeta administration. Furthermore, NaHS exerted a beneficial effect on inhibition of IkappaB-alpha degradation and subsequent activation of transcription factor nuclear factor kappaB (NF-kappaB), as well as inhibition of extracellular signal-regulated kinase (ERK1/2) activity and p38 MAPK activity but not c-Jun N-terminal kinase (JNK) activity induced by Abeta. These results demonstrate that NaHS might be a potential agent for treatment of neuroinflammation-related AD

(65) Nolla-Ardevol V, Strous M, Tegetmeyer HE. Anaerobic digestion of the microalga Spirulina at extreme alkaline conditions: biogas production, metagenome, and metatranscriptome. Front Microbiol 2015;6:597. Abstract: A haloalkaline anaerobic microbial community obtained from soda lake sediments was used to inoculate anaerobic reactors for the production of methane rich biogas. The microalga Spirulina was successfully digested by the haloalkaline microbial consortium at alkaline conditions (pH 10, 2.0 M Na(+)). Continuous biogas production was observed and the obtained biogas was rich in methane, up to 96%. Alkaline medium acted as a CO2 scrubber which resulted in low amounts of CO2 and no traces of H2S in the produced biogas. A hydraulic retention time (HRT) of 15 days and 0.25 g Spirulina L(-1) day(-1) organic loading rate (OLR) were identified as the optimal operational parameters. Metagenomic and metatranscriptomic analysis showed that the hydrolysis of the supplied substrate was mainly carried out by Bacteroidetes of the "ML635J-40 aquatic group" while the hydrogenotrophic pathway was the main producer of methane in a methanogenic community dominated by Methanocalculus

(66) Knossow N, Blonder B, Eckert W, Turchyn AV, Antler G, Kamyshny A, Jr. Annual sulfur cycle in a warm monomictic lake with sub-millimolar sulfate concentrations. Geochem Trans 2015;16:7. Abstract: BACKGROUND: We studied the annual variability of the concentration and isotopic composition of main sulfur species and sulfide oxidation intermediates in the water column of monomictic fresh-water Lake Kinneret. Sulfate concentrations in the lake are <1 mM and similar to concentrations that are proposed to have existed in the Paleoproterozoic ocean. The main goal of this research was to explore biogeochemical constrains of sulfur cycling in the modern low-sulfate fresh-water lake and to identify which processes may be responsible for the isotopic composition of sulfur species in the Precambrian sedimentary rocks. RESULTS: At the deepest point of the lake, the sulfate inventory decreases by more than 20% between March and December due to microbial sulfate reduction leading to the buildup of hydrogen sulfide. During the initial stages of stratification, sulfur isotope fractionation between sulfate and hydrogen sulfide is low (11.6 per thousand) and sulfur oxyanions (e.g. thiosulfate and sulfite) are the main products of the incomplete oxidation of hydrogen sulfide. During the stratification and at the beginning of the lake mixing (July-December), the inventory of hydrogen sulfide as well as of sulfide oxidation intermediates in the water column increases and is accompanied by an increase in sulfur

26

isotope fractionation to 30 +/- 4 per thousand in October. During the period of erosion of the chemocline, zero-valent sulfur prevails over sulfur oxyanions. In the terminal period of the mixing of the water column (January), the concentration of hydrogen sulfide decreases, the inventory of sulfide oxidation intermediates increases, and sulfur isotope fractionation decreases to 20 +/- 2 per thousand. CONCLUSIONS: Sulfide oxidation intermediates are present in the water column of Lake Kinneret at all stages of stratification with significant increase during the mixing of the water column. Hydrogen sulfide inventory in the water column increases from March to December, and sharply decreases during the lake mixis in January. Sulfur isotope fractionation between sulfate and hydrogen sulfide as well as concentrations of sulfide oxidation intermediates can be explained either by microbial sulfate reduction alone or by microbial sulfate reduction combined with microbial disproportionation of sulfide oxidation intermediates. Our study of sulfur cycle in Lake Kinneret may be useful for understanding the range of biogeochemical processes in low sulfate oceans over Earth history

(67) Zhao Y, Pacheco A, Xian M. Medicinal Chemistry: Insights into the Development of Novel H2S Donors. Handb Exp Pharmacol 2015;230:365-88. Abstract: Hydrogen sulfide (H2S) was traditionally considered as a toxic gas. However, recent studies have demonstrated H2S is an endogenously generated gaseous signaling molecule (gasotransmitter) with importance on par with that of two other well-known endogenous gasotransmitters, nitric oxide (NO) and carbon monoxide (CO). Although H2S's exact mechanisms of action are still under investigation, the production of endogenous H2S and the exogenous administration of H2S have been demonstrated to elicit a wide range of physiological responses including modulation of blood pressure and protection of ischemia reperfusion injury, exertion of anti-inflammatory effects, and reduction of metabolic rate. These results strongly suggest that modulation of H2S levels could have potential therapeutic values. In this regard, synthetic H2S-releasing agents (i.e., H2S donors) are not only important research tools, but also potential therapeutic agents. This chapter summarizes the knowledge of currently available H2S donors. Their preparation, H2S releasing mechanisms, and biological applications are discussed

(68) Whiteman M, Perry A, Zhou Z, Bucci M, Papapetropoulos A, Cirino G, et al. Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors. Handb Exp Pharmacol 2015;230:337-63. Abstract: Hydrogen sulfide is rapidly emerging as a key physiological mediator and potential therapeutic tool in numerous areas such as acute and chronic inflammation, neurodegenerative and cardiovascular disease, diabetes, obesity and cancer. However, the vast majority of the published studies have employed crude sulfide salts such as sodium hydrosulfide (NaSH) and sodium sulfide (Na2S) as H2S "donors" to generate H2S. Although these salts are cheap, readily available and easy to use, H2S generated from them occurs as an instantaneous and pH-dependent dissociation, whereas endogenous H2S synthesis from the enzymes cystathionine gamma-lyase, cystathionine-beta-synthase and 3-mercaptopyruvate sulfurtransferase is a slow and sustained process. Furthermore, sulfide salts are frequently used at concentrations (e.g. 100 muM to 10 mM) far in excess of the levels of H2S reported in vivo (nM to low muM). For the therapeutic potential of H2S is to be properly harnessed, pharmacological agents which generate H2S in a physiological manner and deliver physiologically relevant concentrations are needed. The phosphorodithioate GYY4137 has been proposed as "slow-release" H2S donors and has shown promising efficacy in cellular and animal model diseases such as hypertension, sepsis, atherosclerosis, neonatal lung injury and cancer. However, H2S generation from GYY4137 is inefficient necessitating its use at high concentrations/doses. However, structural modification of the phosphorodithioate core has led to compounds (e.g. AP67 and AP105) with accelerated rates of H2S generation and enhanced biological activity. In this review, the therapeutic potential and limitations of GYY4137 and related phosphorodithioate derivatives are discussed

27

(69) Wen YD, Zhu YZ. The Pharmacological Effects of S-Propargyl-Cysteine, a Novel Endogenous H2S-Producing Compound. Handb Exp Pharmacol 2015;230:325-36. Abstract: S-propargyl-cysteine (SPRC), also named as ZYZ-802, is a structural analog of S-allylcysteine (SAC), the most abundant constituent of aged garlic extract. SPRC becomes a derivative of the amino acid cysteine, which contains sulfur atom, by changing allyl group in SAC to propargyl group in SPRC. Another analog of SPRC and SAC is S-propyl cysteine (SPC), which has propyl group instead in its cysteine structure. Drug formulation of SPRC has been investigated in the mixture of extenders, such as lactose, microcrystalline cellulose, and cross-linked povidone, showing good fluidity and scale-up production possibility. Controlled release formulation of SPRC (CR-SPRC) and leonurine-SPRC were invented and shown the decent pharmacological effects in heart failure and hypoxia injury, respectively. The pharmacological effects of SPRC have been shown that cardioprotection and proangiogenesis in several ischemic heart models, neuroprotection in Alzheimer's disease, proapoptosis in gastric cancer and anti-inflammation in acute pancreatitis. Moreover, CR-SPRC reduced infarct size and recovered partial cardiac function in heart failure rat model. Leonurine-SPRC protected hypoxic neonatal rat ventricular myocytes in much lower dose. Interestingly, since the propagyl group in SPRC has the stronger chemical bond in the cysteine structure than allyl group in SAC and propyl group in SPC, SPRC showed more extensive cardioprotection in ischemic rat hearts model compared to SAC and SPC. The mechanisms of pharmacological effects of SPRC have been unveiled that SPRC reduced Ca(2+) accumulation, activated antioxidants, inhibited STAT3, decreased inflammatory cytokines, and elevated p53 and Bax. More pharmacological effects and mechanisms of SPRC will be discovered in atherosclerosis, hypertension, and other diseases

(70) Feng W, Dymock BW. Fluorescent Probes for H2S Detection and Quantification. Handb Exp Pharmacol 2015;230:291-323. Abstract: Many diverse, sensitive and structurally novel fluorescent probes have recently been reported for H2S detection. Quantification of H2S requires a selective chemosensor which will react only with H2S against a background of high concentrations of other thiols or reducing agents. Most published probes are able to quantify H2S selectively in a simple in vitro system with the most sensitive probes able to detect H2S at below 100 nM concentrations. A subset of probes also have utility in sensing H2S in living cells, and there are now several with specific sub-cellular localization and a few cases of in vivo applications. Biologists studying H2S now have a wide range of tools to assist them to aid further understanding of the role of H2S in biology

(71) Qabazard B, Sturzenbaum SR. H2S: A New Approach to Lifespan Enhancement and Healthy Ageing? Handb Exp Pharmacol 2015;230:269-87. Abstract: Ageing, a progressive structural and functional decline, is considered to be a major risk factor for virtually all ageing-associated pathologies and disabilities, including Alzheimer's disease, Parkinson's disease, stroke, diabetes, atherosclerosis and certain cancers. Biogerontology research has now been largely directed towards finding novel drug targets to decelerate the ageing process and attain healthy ageing in order to delay the onset of all ageing-related diseases. H2S has been reported to exert vasodilatory, antioxidant, antiapoptotic and anti-inflammatory actions and has been shown to act as a signalling molecule, neuromodulator and cytoprotectant. Intriguingly, H2S has been reported to regulate cell cycle and survival in healthy cells which suggests that it may regulate cell fate and hence the ageing process. This chapter sets out to provide an overview of the current knowledge regarding the involvement of H2S in ageing, with a specific focus on the invertebrate model nematode C. elegans

(72) Lee ZW, Deng LW. Role of H2S Donors in Cancer Biology. Handb Exp Pharmacol 2015;230:243-65. Abstract: Hydrogen sulfide (H2S) donors including organosulfur compounds (OSC), inorganic sulfide salts, and synthetic compounds are useful tools in studies to elucidate the

28

effects of H2S in cancer biology. Studies using such donors have shown the ability of H2S to suppress tumor growth both in vitro and in vivo, with some of them suggesting the selectivity of its cytotoxic effects to cancer cells. In addition to promoting cancer cell death, H2S donors were also found to inhibit cancer angiogenesis and metastasis. The underlying mechanisms for the anticancer activities of H2S involve (1) cell signaling pathways, such as MAPK and STAT; (2) cell cycle regulation; (3) microRNAs regulation; and (4) cancer metabolism and pH regulation. Altogether, compiling evidences have demonstrated the great potential of using H2S donors as anticancer agents. Nevertheless, the application and development of H2S for therapy are still facing challenges as identification of molecular targets of H2S awaits further investigation

(73) Hellmich MR, Szabo C. Hydrogen Sulfide and Cancer. Handb Exp Pharmacol 2015;230:233-41. Abstract: Recent studies revealed increased expression of various hydrogen sulfide (H2S)-producing enzymes in cancer cells of various tissue types, and new roles of H2S in the pathophysiology of cancer have emerged. This is particularly evident in cancers of the colon and ovaries, where the malignant cells both overexpress cystathionine-beta-synthase (CBS) and produce increased amounts of H2S, which enhances tumor growth and spread by (a) stimulating cellular bioenergetics, (b) activating proliferative, migratory, and invasive signaling pathways, and (c) enhancing tumor angiogenesis. Importantly, in preclinical models of these cancers, either pharmacological inhibition or genetic silencing of CBS was shown to be sufficient to suppress cancer cell bioenergetics in vitro, inhibit tumor growth and metastasis in vivo, and enhance the antitumor efficacy of frontline chemotherapeutic agents, providing a strong rationale for the development of CBS-targeted inhibitors as anticancer therapies. However, the observation that inhibition of H2S biosynthesis exerts anticancer effects is contradicted by other studies showing that increasing H2S with exogenous donors also exerts antitumor actions. Herein, we present a brief review of the scientific literature documenting the function of H2S, H2S donors, and transsulfuration enzymes in cancers from various tissue types, and propose that the paradoxical actions of H2S can be resolved by considering the bell-shaped pharmacology of H2S, whereby lower (endogenous) H2S production tends to promote, while higher (generated from exogenously added H2S donors) tends to inhibit cancer cell proliferation. Finally, we suggest areas for future investigations to expand our knowledge of this nascent field

(74) Terada Y, Kawabata A. H2S and Pain: A Novel Aspect for Processing of Somatic, Visceral and Neuropathic Pain Signals. Handb Exp Pharmacol 2015;230:217-30. Abstract: Hydrogen sulfide (H2S) formed by multiple enzymes including cystathionine-gamma-lyase (CSE) targets Cav3.2 T-type Ca(2+) channels (T-channels) and transient receptor potential ankyrin-1 (TRPA1). Intraplantar and intracolonic administration of H2S donors promotes somatic and visceral pain, respectively, via activation of Cav3.2 and TRPA1 in rats and/or mice. Injection of H2S donors into the plantar tissues, pancreatic duct, colonic lumen, or bladder causes T-channel-dependent excitation of nociceptors, determined as phosphorylation of ERK or expression of Fos in the spinal dorsal horn. Electrophysiological studies demonstrate that exogenous and/or endogenous H2S facilitates membrane currents through T-channels in NG108-15 cells and isolated mouse dorsal root ganglion (DRG) neurons that abundantly express Cav3.2 and also in Cav3.2-transfected HEK293 cells. In mice with cerulein-induced pancreatitis and cyclophosphamide-induced cystitis, visceral pain and/or referred hyperalgesia are inhibited by CSE inhibitors and by pharmacological blockade or genetic silencing of Cav3.2, and CSE protein is upregulated in the pancreas and bladder. In rats with neuropathy induced by L5 spinal nerve cutting or by repeated administration of paclitaxel, an anticancer drug, the neuropathic hyperalgesia is reversed by inhibitors of CSE or T-channels and by silencing of Cav3.2. Upregulation of Cav3.2 protein in DRG is detectable in the former, but not in the latter, neuropathic pain models. Thus, H2S appears to function as a nociceptive messenger by facilitating functions of Cav3.2 and TRPA1, and the enhanced function of the

29

CSE/H2S/Cav3.2 pathway is considered to be involved in the pancreatitis- and cystitis-related pain and in neuropathic pain

(75) Nagpure BV, Bian JS. Brain, Learning, and Memory: Role of H2S in Neurodegenerative Diseases. Handb Exp Pharmacol 2015;230:193-215. Abstract: For more than 300 years, the toxicity of hydrogen sulfide (H2S) has been known to mankind. However, this point of view is changing as an increased interest was observed in H2S biology in the last two decades. The scientific community has succeeded to unravel many important physiological and pathological effects of H2S on mammalian body systems. Thus, H2S is now referred to as a third endogenous gaseous mediator along with nitric oxide and carbon monoxide. Acting as a neuromodulator, H2S facilitates long-term potentiation and regulates intracellular calcium levels, which are important processes in learning and memory. Aberrant endogenous production and metabolism of H2S are implicated in pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). Various H2S donors have shown beneficial therapeutic effects in neurodegenerative disease models by targeting hallmark pathological events (e.g., amyloid-beta production in AD and neuroinflammation in PD). The results obtained from many in vivo studies clearly show that H2S not only prevents neuronal and synaptic deterioration but also improves deficits in memory, cognition, and learning. The anti-inflammatory, antioxidant, and anti-apoptotic effects of H2S underlie its neuroprotective properties. In this chapter, we will overview the current understanding of H2S in context of neurodegenerative diseases, with special emphasis on its corrective effects on impaired learning, memory, and cognition

(76) Kida K, Ichinose F. Hydrogen Sulfide and Neuroinflammation. Handb Exp Pharmacol 2015;230:181-9. Abstract: The innate and adaptive immune system plays an important role in diverse forms of central nervous system (CNS) pathologies including neurodegenerative diseases and peripheral nerve injury. Evidence for an innate inflammatory response in Alzheimer's disease (AD) was described 20 years ago, and subsequent studies have documented roles of inflammation in Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and a growing number of other CNS pathologies. Although inflammation may not be the initiating factor for neurodegenerative pathologies, experimental data suggests that persistent inflammatory responses involving microglia and astrocytes, as well as blood monocyte-derived macrophages, clearly contribute to disease progression.High levels of hydrogen sulfide exert toxic effects to CNS. On the other hand, low and physiological levels of H2S may have beneficial effects on number of tissues including CNS. For example, a number of studies have reported that H2S exerts anti-inflammatory and anti-apoptotic effects in CNS. In this chapter, studies related to the role of H2S in neuroinflammation and neurodegeneration will be reviewed and discussed. In particular, we will focus on the role of H2S in neuroinflammation associated with PD

(77) Bhatia M. H2S and Inflammation: An Overview. Handb Exp Pharmacol 2015;230:165-80. Abstract: Inflammation is a response to traumatic, infectious, post-ischemic, toxic, or autoimmune injury. However, uncontrolled inflammation can lead to disease, and inflammation is now believed to be responsible for several disease conditions. Research in our laboratory has shown that hydrogen sulfide (H2S) acts as a novel mediator of inflammation. At present, work in several research groups worldwide is focused on determining the role of H2S in inflammation. H2S has been implicated in different inflammatory conditions. Most of this research involved working with animal models of disease and in vitro systems. Recent research, however, points to a role of H2S in clinical inflammatory disease as well. This chapter describes our current understanding of the role of H2S in inflammation

(78) Emerson M. Hydrogen Sulfide and Platelets: A Possible Role in Thrombosis. Handb Exp Pharmacol 2015;230:153-62.

30

Abstract: Platelets are circulating blood elements with key roles in haemostasis and thrombosis. Platelets are activated by a range of stimuli including exposed subendothelial components. Haemostasis also depends upon the effects of inhibitory substances, including the gasotransmitter nitric oxide whose effects on platelets are well documented. Evidence is also emerging to suggest that H2S is generated enzymatically by platelets and can impact their function. Exposure of platelets to H2S from slow-release compounds inhibits aggregation and exerted anti-thrombotic effects in vivo. The mechanisms by which H2S impacts platelet function and the importance of interactions between H2S and other gasotransmitters remain unclear. H2S is therefore emerging as a potentially important regulator of platelet activation and thrombosis. Further study is required to evaluate its importance as a regulator of platelet physiology and associated pathological conditions such as myocardial infarction and stroke

(79) Tao BB, Cai WJ, Zhu YC. H2S Is a Promoter of Angiogenesis: Identification of H2S "Receptors" and Its Molecular Switches in Vascular Endothelial Cells. Handb Exp Pharmacol 2015;230:137-52. Abstract: Angiogenesis is a physiological process in organ development and also a compensatory response in ischemia. When ischemia occurs, oxygen sensors in vascular endothelial cells sense the decrease in oxygen, thus activating downstream signaling pathways to promote the proliferation, migration, and tube formation of the endothelial cells. The new vasculatures are formed by sprouting from preexisting vessels, in order to maintain oxygen homeostasis in ischemic tissues (Folkman and Shing 1992). Collateral circulation is sometimes established under chronic ischemic conditions such as chronic myocardial ischemia (Banai et al. 1994). However, naturally occurring angiogenesis is usually not sufficient to compensate for ischemia in ischemic tissues. Proangiogenic drugs may be useful to promote angiogenesis in these diseases

(80) di Villa BR, Cirino G, Sorrentino R. Hydrogen Sulfide and Urogenital Tract. Handb Exp Pharmacol 2015;230:111-36. Abstract: In this chapter the role played by H2S in the physiopathology of urogenital tract revising animal and human data available in the current relevant literature is discussed. H2S pathway has been demonstrated to be involved in the mechanism underlying penile erection in human and experimental animal. Both cystathionine-beta synthase (CBS) and cystathionine-gamma lyase (CSE) are expressed in the human corpus cavernosum and exogenous H2S relaxes isolated human corpus cavernosum strips in an endothelium-independent manner. Hydrogen sulfide pathway also accounts for the direct vasodilatory effect operated by testosterone on isolated vessels. Convincing evidence suggests that H2S can influence the cGMP pathway by inhibiting the phosphodiesterase 5 (PDE-5) activity. All these findings taken together suggest an important role for the H2S pathway in human corpus cavernosum homeostasis. However, H2S effect is not confined to human corpus cavernosum but also plays an important role in human bladder. Human bladder expresses mainly CBS and generates in vitro detectable amount of H2S. In addition the bladder relaxant effect of the PDE-5 inhibitor sildenafil involves H2S as mediator.In conclusion the H2S pathway is not only involved in penile erection but also plays a role in bladder homeostasis. In addition the finding that it involved in the mechanism of action of PDE-5 inhibitors strongly suggests that modulation of this pathway can represent a therapeutic target for the treatment of erectile dysfunction and bladder diseases

(81) Yang G, Wang R. H2S and Blood Vessels: An Overview. Handb Exp Pharmacol 2015;230:85-110. Abstract: The physiological and biomedical importance of hydrogen sulfide (H2S) has been fully recognized in the cardiovascular system as well as in the rest of the body. In blood vessels, cystathionine gamma-lyase (CSE) is a major H2S-producing enzyme expressed in both smooth muscle and endothelium as well as periadventitial adipose tissues. Regulation of H2S production from CSE is controlled by a complex integration of transcriptional,

31

posttranscriptional, and posttranslational mechanisms in blood vessels. In smooth muscle cells, H2S regulates cell apoptosis, phenotypic switch, relaxation and contraction, and calcification. In endothelial cells, H2S controls cell proliferation, cellular senescence, oxidative stress, inflammation, etc. H2S interacts with nitric oxide and acts as an endothelium-derived relaxing factor and an endothelium-derived hyperpolarizing factor. H2S generated from periadventitial adipose tissues acts as an adipocyte-derived relaxing factor and modulates the vascular tone. Extensive evidence has demonstrated the beneficial roles of the CSE/H2S system in various blood vessel diseases, such as hypertension, atherosclerosis, and aortic aneurysm. The important roles signaling in the cardiovascular system merit further intensive and extensive investigation. H2S-releasing agents and CSE activators will find their great applications in the prevention and treatment of blood vessel-related disorders

(82) Kimura H. Physiological Roles of Hydrogen Sulfide and Polysulfides. Handb Exp Pharmacol 2015;230:61-81. Abstract: Hydrogen sulfide (H2S) has been recognized as a signaling molecule as well as a cytoprotective molecule. H2S modulates neurotransmission, regulates vascular tone, protects various tissues and organs, regulates inflammation, induces angiogenesis, and detects cellular oxygen levels. H2S is produced from L-cysteine by cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) together with cysteine aminotransferase (CAT). Recently, a novel pathway for the production of H2S from D-cysteine was identified, involving D-amino acid oxidase (DAO) together with 3MST. Sulfuration (also called sulfhydration), which adds sulfur atoms to the cysteine residues of target proteins to modify protein activity, has been extensively studied as a mode of H2S action. Recently, hydrogen polysulfides (H2Sn, where n = 3-7; n = 2 is termed as persulfide) have been found to sulfurate target proteins in the brain, including transient receptor potential ankyrin 1 (TRPA1) channels, Kelch-like ECH-associating protein 1 (Keap1), and phosphatase and tensin homolog (PTEN), much more potently than H2S. The physiological stimuli that trigger the production of H2S and polysulfides, and the mechanisms maintaining their local levels, remain unknown. Understanding the regulation of H2Sn (including H2S) production, and the specific stimuli that induce their release, will provide new insight into the biology of H2S and will provide novel avenues for therapeutic development in diseases involving H2S-related substances

(83) Filipovic MR. Persulfidation (S-sulfhydration) and H2S. Handb Exp Pharmacol 2015;230:29-59. Abstract: The past decade has witnessed the discovery of hydrogen sulfide (H2S) as a new signalling molecule. Its ability to act as a neurotransmitter, regulator of blood pressure, immunomodulator or anti-apoptotic agent, together with its great pharmacological potential, is now well established. Notwithstanding the growing body of evidence showing the biological roles of H2S, the gap between the macroscopic descriptions and the actual mechanism(s) behind these processes is getting larger. The reactivity towards reactive oxygen and nitrogen species and/or metal centres cannot explain this plethora of biological effects. Therefore, a mechanism involving modification of protein cysteine residues to form protein persulfides is proposed. It is alternatively called S-sulfhydration. Persulfides are not particularly stable and show increased reactivity when compared to free thiols. Detection of protein persulfides is still facing methodological limitations, and mechanisms by which H2S causes this modification are still largely scarce. Persulfidation of protein such as KATP could contribute to H2S-induced vasodilation, while S-sulfhydration of GAPDH and NF-kappaB inhibits apoptosis. H2S regulates endoplasmic reticulum stress by causing persulfidation of PTP-1B. Several other proteins have been found to be regulated by this posttranslational modification of cysteine. This review article provides a critical overview of the current state of the literature addressing protein S-sulfhydration, with particular emphasis on the challenges and future research directions in this particular field

32

(84) Huang CW, Moore PK. H2S Synthesizing Enzymes: Biochemistry and Molecular Aspects. Handb Exp Pharmacol 2015;230:3-25. Abstract: Hydrogen sulfide (H2S) is a biologically active gas that is synthesized naturally by three enzymes, cystathionine gamma-lyase (CSE), cystathionine beta-synthetase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). These enzymes are constitutively present in a wide array of biological cells and tissues and their expression can be induced by a number of disease states. It is becoming increasingly clear that H2S is an important mediator of a wide range of cell functions in health and in disease. This review therefore provides an overview of the biochemical and molecular regulation of H2S synthesizing enzymes both in physiological conditions and their modulation in disease states with particular focus on their regulation in asthma, atherosclerosis and diabetes. The importance of small molecule inhibitors in the study of molecular pathways, the current use of common H2S synthesizing enzyme inhibitors and the relevant characteristics of mice in which these enzymes have been genetically deleted will also be summarized. With a greater understanding of the molecular regulation of these enzymes in disease states, as well as the availability of novel small molecules with high specificity targeted towards H2S producing enzymes, the potential to regulate the biological functions of this intriguing gas H2S for therapeutic effect can perhaps be brought one step closer

(85) Wang G, Li W, Chen Q, Jiang Y, Lu X, Zhao X. Hydrogen sulfide accelerates wound healing in diabetic rats. Int J Clin Exp Pathol 2015;8(5):5097-104. Abstract: AIM: The aim of this study was to explore the role of hydrogen sulfide on wound healing in diabetic rats. METHODS: Experimental diabetes in rats was induced by intraperitoneal injection of streptozotocin (STZ) (in 0.1 mol/L citrate buffer, Ph 4.5) at dose of 70 mg/kg. Diabetic and age-matched non-diabetic rats were randomly assigned to three groups: untreated diabetic controls (UDC), treated diabetic administrations (TDA), and non-diabetic controls (NDC). Wound Healing Model was prepared by making a round incision (2.0 cm in diameter) in full thickness. Rats from TDA receive 2% sodium bisulfide ointment on wound, and animals from UDC and NDC receive control cream. After treatment of 21 days with sodium bisulfide, blood samples were collected for determination of vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), antioxidant effects. Granulation tissues from the wound were processed for histological examination and analysis of western blot. RESULTS: The study indicated a significant increase in levels of VEGF and ICAM-1 and a decline in activity of coagulation in diabetic rats treated with sodium bisulfide. Sodium bisulfide treatment raised the activity of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein expression, and decreased tumor necrosis factor alpha (TNF-alpha) protein expression in diabetic rats. CONCLUSIONS: The findings in present study suggested that hydrogen sulfide accelerates the wound healing in rats with diabetes. The beneficial effect of H2S may be associated with formation of granulation, anti-inflammation, antioxidant, and the increased level of vascular endothelial growth factor (VEGF)

(86) Kaur M, Sachdeva S, Bedi O, Kaur T, Kumar P. Combined effect of hydrogen sulphide donor and losartan in experimental diabetic nephropathy in rats. J Diabetes Metab Disord 2015;14:63. Abstract: BACKGROUND: Diabetic nephropathy (DN) is one of the complex complications of Diabetes Mellitus (DM). The present study has been designed to examine protective role of hydrogen Sulphide (H2S) donor against streptozotocin (STZ) -induced behavioral, oxidative abnormalities and its DN like symptoms in rats. METHODS: For the induction of DN single intraperitoneal administration of STZ (45 mg/kg) was given till third week. Behavioral parameters were measured on 1st, 7th, 21st and 42nd days and biochemical parameters were performed on 42nd day. All the drug treatments [NaHS (10 & 30 mumol/kg i.p), DL-propargylglycine (10 mg/kg i.p), standard drug- Losartan (5 mg/kg p.o)] were given for 3 weeks staring from 21st day after the STZ injection. RESULTS: Three weeks treatment with sodium hydrosulphide (NaHS) (10 and 30 mumol/kg i.p,) significantly attenuated the behavioral and biochemical abnormalities in STZ-treated animals.

33

DL-propargylglycine (10 mg/kg i.p) pretreatment with sub-effective dose of NaHS (30 mumol/kg i.p) significantly reversed the protective effect of NaHS. However, combination of both NaHS (30 mumol/kg i.p) and standard drug losartan (5 mg/kg p.o) potentiated their effects as compared to their effect alone. CONCLUSION: The results of the present study suggest that H2S treatment showed significant improvement in behavioral and biochemical abnormalities induced by STZ administration. Thus H2S represents a target of treatment to prevent the progression of complications by DN

(87) Basic A, Blomqvist S, Carlen A, Dahlen G. Estimation of bacterial hydrogen sulfide production in vitro. J Oral Microbiol 2015;7:28166. Abstract: Oral bacterial hydrogen sulfide (H2S) production was estimated comparing two different colorimetric methods in microtiter plate format. High H2S production was seen for Fusobacterium spp., Treponema denticola, and Prevotella tannerae, associated with periodontal disease. The production differed between the methods indicating that H2S production may follow different pathways