Hydrogen sulfide responsive nanoplatforms: Novel gas responsive drug delivery carriers for biomedical applications

Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.

Absorption characteristics,model,and molecular mechanism of hydrogen sulfide in morpholine acetate aqueous solution

The solubility of H_(2)S was measured in solutions of N-butyl-N-methylmorpholine acetate([Bmmorp][Ac])containing 20%-40%(mass)water at experimental temperatures ranged from 298.15 to 328.15 K and pressures up to 320 k Pa.The total solubility of H_(2)S increased with higher temperatures,lower pressures,and reduced water content.The reaction equilibrium thermodynamic model was used to correlate the solubility data.The results indicate that the chemical reaction equilibrium constant decrease with increasing water content and temperature,whereas Henry constant increase with increasing water content and temperature.Compared with other ionic liquids,H_(2)S exhibits a higher physical absorption enthalpy and a lower chemical absorption enthalpy in[Bmmorp][Ac]aqueous solution.This suggests that[Bmmorp][Ac]has a strong physical affinity for H_(2)S and low energy requirement for desorption.Quantum chemical methods were used to investigate the molecular mechanism of H_(2)S absorption in ionic liquids.The interaction energy analysis revealed that the binding of H_(2)S with the ionic liquid in a1:2 ratio is more stable.Detailed analyses by the methods of the interaction region indicator and the atoms in molecules were conducted to the interactions between H_(2)S and the ionic liquid.

Application and Regeneration of a Non-Aqueous System of Cu/HCl and DMF for the Oxidation of Hydrogen Sulfide in Natural Gas

A copper-based non-aqueous-phase desulfurization agent is prepared by adding CuCl_(2) to the solvent N,Ndimethylformamide(DMF).Static desulfurization experiments show that the agent has high efficiency.However,the desulfurization reaction leads to the formation of a copper sulfide precipitate.It is found that the addition of chloride ions in the form of hydrochloric acid or potassium chloride prevents the formation of copper sulfide,and elemental sulfur is precipitated instead.The efficient absorption of H2S by the Cu/HCl–DMF agent relies on the rapid coordination of Cu^(2+)with DMF,Cl^(−),and H2S molecules to form a[Cu(DMF)_(n−p)(HS−)_(p)(Cl−)_(m)]_((2−p−m))+complex.The desulfurization agent has a sulfur capacity of up to 9.81 g/L when used in static bubble desulfurization at atmospheric pressure.The system has low viscosity and good chemical and thermal stability.It can be rapidly regenerated through continuous oxidation.After five repetitions of the regeneration procedure,the sulfur capacity reaches more than 91%of the initial capacity,indicating the potential of the system for commercial applications.

Dissecting molecular mechanisms underlying ferroptosis in human umbilical cord mesenchymal stem cells:Role of cystathionineγ-lyase/hydrogen sulfide pathway

BACKGROUND Ferroptosis can induce low retention and engraftment after mesenchymal stem cell(MSC)delivery,which is considered a major challenge to the effectiveness of MSC-based pulmonary arterial hypertension(PAH)therapy.Interestingly,the cystathionineγ-lyase(CSE)/hydrogen sulfide(H_(2)S)pathway may contribute to mediating ferroptosis.However,the influence of the CSE/H_(2)S pathway on ferroptosis in human umbilical cord MSCs(HUCMSCs)remains unclear.AIM To clarify whether the effect of HUCMSCs on vascular remodelling in PAH mice is affected by CSE/H_(2)S pathway-mediated ferroptosis,and to investigate the functions of the CSE/H_(2)S pathway in ferroptosis in HUCMSCs and the underlying mechanisms.METHODS Erastin and ferrostatin-1(Fer-1)were used to induce and inhibit ferroptosis,respectively.HUCMSCs were transfected with a vector to overexpress or inhibit expression of CSE.A PAH mouse model was established using 4-wk-old male BALB/c nude mice under hypoxic conditions,and pulmonary pressure and vascular remodelling were measured.The survival of HUCMSCs after delivery was observed by in vivo bioluminescence imaging.Cell viability,iron accumulation,reactive oxygen species production,cystine uptake,and lipid peroxidation in HUCMSCs were tested.Ferroptosis-related proteins and S-sulfhydrated Kelchlike ECH-associating protein 1(Keap1)were detected by western blot analysis.RESULTS In vivo,CSE overexpression improved cell survival after erastin-treated HUCMSC delivery in mice with hypoxiainduced PAH.In vitro,CSE overexpression improved H_(2)S production and ferroptosis-related indexes,such as cell viability,iron level,reactive oxygen species production,cystine uptake,lipid peroxidation,mitochondrial membrane density,and ferroptosis-related protein expression,in erastin-treated HUCMSCs.In contrast,in vivo,CSE inhibition decreased cell survival after Fer-1-treated HUCMSC delivery and aggravated vascular remodelling in PAH mice.In vitro,CSE inhibition decreased H_(2)S levels and restored ferroptosis in Fer-1-treated HUCMSCs.Interestingly,upregulation of the CSE/H_(2)S pathway induced Keap1 S-sulfhydration,which contributed to the inhibition of ferroptosis.CONCLUSION Regulation of the CSE/H_(2)S pathway in HUCMSCs contributes to the inhibition of ferroptosis and improves the suppressive effect on vascular remodelling in mice with hypoxia-induced PAH.Moreover,the protective effect of the CSE/H_(2)S pathway against ferroptosis in HUCMSCs is mediated via S-sulfhydrated Keap1/nuclear factor erythroid 2-related factor 2 signalling.The present study may provide a novel therapeutic avenue for improving the protective capacity of transplanted MSCs in PAH.

Measurement and model of density,viscosity,and hydrogen sulfide solubility in ferric chloride/trioctylmethylammonium chloride ionic liquid

The density and viscosity of ferric chloride/trioctylmethylammonium chloride ionic liquid(rFeCl_(3)/[A336]Cl)with different molar ratios(r=0.1-0.8)of FeCl_(3) to[A336]Cl were measured at temperatures from 313.15 to 358.15 K and atmospheric pressure.The density and viscosity data were fitted by the relevant temperature variation equations,respectively.The variation of density and viscosity with temperature and r was obtained.The solubility of rFeCl_(3)/[A336]Cl to H_2S was measured at temperatures from 318.15 to 348.15 K and pressures from 0 to 150 kPa.The effects of temperature,pressure,and r on the solubility of H_(2)S were discussed.The reaction equilibrium thermodynamic model(RETM)was used to fit the H_(2)S solubility data,and the average relative error was less than 1.3%,indicating that the model can relate the solubility data well.And Henry's constant and chemical reaction equilibrium constant were obtained by the RETM fitting.The relationships of Henry's constant and chemical reaction equilibrium constant with temperature and r were analyzed.

Effect of exogenous hydrogen sulfide in the nucleus tractus solitarius on gastric motility in rats

BACKGROUND Hydrogen sulfide(H2S)is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems.It exerts its effects through multiple signaling pathways,impacting various physiological activities.The nucleus tractus solitarius(NTS),a vital nucleus involved in visceral sensation,was investigated in this study to understand the role of H2S in regulating gastric function in rats.AIM To examine whether H2S affects the nuclear factor kappa-B(NF-κB)and transient receptor potential vanilloid 1 pathways and the neurokinin 1(NK1)receptor in the NTS.METHODS Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase(CBS)and c-Fos co-expressed positive neurons in the NTS during rat stress.Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus.Changes in gastric motility were observed before and after injecting different doses of NaHS(4 nmol and 8 nmol),physiological saline,Capsazepine(4 nmol)+NaHS(4 nmol),pyrrolidine dithiocarbamate(PDTC,4 nmol)+NaHS(4 nmol),and L703606(4 nmol)+NaHS(4 nmol).RESULTS We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group.Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats(P<0.01).However,injection of saline,first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1(TRPV1)antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes(P>0.05).CONCLUSION NTS contains neurons co-expressing CBS and c-Fos,and the injection of NaHS into the NTS can suppress gastric motility in rats.This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.

β-Cyclodextrin-Based Nitrosoglutathione Improves the Storage Quality of Peach by Regulating the Metabolism of Endogenous Nitric Oxide, Hydrogen Sulfide, and Phenylpropane

Nitrosoglutathione(GSNO)andβ-cyclodextrin(β-CD)exhibit positive roles in regulating fruit quality.However,there are few reports about the effects of GSNO andβ-CD on enhancing storability and boosting nitric oxide(NO),hydrogen sulfide(H2S),and phenylpropane metabolism in fruits during storage.“Xintaihong”peach were treated with 0.5,1.0,1.5mmol L−1 GSNO in 0.5%(w/v)β-CD solution(GSNO/β-CD).The effects of GSNO/β-CD on endogenous NO,H2S,and phenylpropane metabolism were investigated.Treatment with GSNO/β-CD increased the color difference of peach and inhibited the increase of respiratory intensity,weight loss,and relative conductivity.Treatment with 1.0 mmol L−1 GSNO/β-CD increased the nitric oxide synthase(NOS-like)activity and L-arginine content,thereby promoting the accumulation of endogenous NO.By improving the activities of L-cysteine desulfhydrylase(L-CD),O-acetylserine sulfur lyase(OAS-TL),serine acetyltransferase(SAT),GSNO/β-CD increased the content of endogenous H2S in peach.Treatment with GSNO/β-CD increased the activities of phenylalanine ammonia-lyase(PAL),4-coumarate-CoA ligase(4CL),and cinnamic acid-4-hydroxylase(C4H),promoted the increase of total phenols,flavonoids,and lignin in peach.These results indicated that GSNO/β-CD treatment better maintained the quality of peach by improving the metabolism of endogenous NO,H2S,and phenylpropane during storage.

Simulation study of hydrogen sulfide removal in underground gas storage converted from the multilayered sour gas field

A simulation study was carried out to investigate the temporal evolution of H_(2)S in the Huangcaoxia underground gas storage (UGS), which is converted from a depleted sulfur-containing gas field. Based on the rock and fluid properties of the Huangcaoxia gas field, a multilayered model was built. The upper layer Jia-2 contains a high concentration of H_(2)S (27.2 g/m^(3)), and the lower layer Jia-1 contains a low concentration of H_(2)S (14.0 mg/m^(3)). There is also a low-permeability interlayer between Jia-1 and Jia-2. The multi-component fluid characterizations for Jia-1 and Jia-2 were implemented separately using the Peng-Robinson equation of state in order to perform the compositional simulation. The H_(2)S concentration gradually increased in a single cycle and peaked at the end of the production season. The peak H_(2)S concentration in each cycle showed a decreasing trend when the recovery factor (RF) of the gas field was lower than 70%. When the RF was above 70%, the peak H_(2)S concentration increased first and then decreased. A higher reservoir RF, a higher maximum working pressure, and a higher working gas ratio will lead to a higher H_(2)S removal efficiency. Similar to developing multi-layered petroleum fields, the operation of multilayered gas storage can also be divided into multi-layer commingled operation and independent operation for different layers. When the two layers are combined to build the storage, the sweet gas produced from Jia-1 can spontaneously mix with the sour gas produced from Jia-2 within the wellbore, which can significantly reduce the overall H_(2)S concentration in the wellstream. When the working gas volume is set constant, the allocation ratio between the two layers has little effect on the H_(2)S removal. After nine cycles, the produced gas’s H_(2)S concentration can be lowered to 20 mg/m^(3). Our study recommends combining the Jia-2 and Jia-1 layers to build the Huangcaoxia underground gas storage. This plan can quickly reduce the H_(2)S concentration of the produced gas to 20 mg/m^(3), thus meeting the gas export standards as well as the HSE (Health, Safety, and Environment) requirements in the field. This study helps the engineers understand the H_(2)S removal for sulfur-containing UGS as well as provides technical guidelines for converting other multilayered sour gas fields into underground storage sites.

Hydrogen Sulfide May Function Downstream of Nitric Oxide in Ethylene-Induced Stomatal Closure in Vicia faba L.

Pharmacological, laser scanning confocal microscopic （LSCM）, and spectrophotographic approaches were used to study the roles of hydrogen sulfide （H2S） and nitric oxide （NO） in signaling transduction of stomatal movement in response to ethylene in Viciafaba L. Ethylene treatment resulted in the dose-dependent stomatal closure under light, and this effect was blocked by the inhibitors of H2S biosynthesis in V. faba L. Additionally, ethylene induces H2S generation and increases L-/D-cysteine desulfhydrase （pyridoxalphosphate-dependent enzyme） activity in leaves of V. faba L. Inhibitors of H2S biosynthesis have no effect on the ethylene-induced stomatal closure, NO accumulation, and nitrate reductase （NR） activity in guard cells or leaves of II. faba L. Moreover, the ethylene-induced increase of H2S levels and L-/D- cysteine desulfhydrase activity declined when NO generation was inhibited. Therefore, we conclude that H2S and NO probably are involved in the signal transduction pathway of ethylene-induced stomatal closure. H2S may represent a novel component downstream of NO in the ethylene-induced stomatal movement in V. faba L.

Hydrogen sulfide protects against amyloid beta-peptide induced neuronal injury via attenuating inflammatory responses in a rat model

Neuroinflammation has been recognized to play a critical role in the pathogenesis of Alzheimer＇s disease （AD）, which is pathologically characterized by the accumulation of senile plaques containing activated microglia and amyloid β-peptides （Aβ）. In the present study, we examined the neuroprotective effects of hydrogen sulfide （H2S） on neuroinflammation in rats with Aβ1-40 hippocampal injection. We found that Aβ-induced rats exhibited a disorder of pyramidal cell layer arrangement, and a decrease of mean pyramidal cell number in the CA1 hippocampal region compared with those in sham operated rats. NaHS （a donor of H2S, 5.6 mg/kg/d, i.p.） treatment for 3 weeks rescued neuronal cell death significantly. Moreover, we found that H2S dramatically suppressed the release of TNF-α, IL-1β and IL-6 in the hippocampus. Consistently, both immunohistochemistry and Western blotting assays showed that H2S inhibited the upregulation of COX-2 and the activation of NF-κB in the hippocampus. In conclusion, our data indicate that H2S suppresses neuroinflammation via inhibition of the NF-κB activation pathway in the Aβ-induced rat model and has potential value for AD therapy.

Kinetics of hydrogen sulfide decomposition in a DBD plasma reactor operated at high temperature

The present study investigates the kinetics of hydrogen sulfide （H2S） decomposition into hydrogen and sulfur carded out in a nonthermal plasma dielectric barrier discharge （NTP-DBD） reactor operated at ,-430 K for in situ removal of sulfur condensed inside the reactor walls. The dissociation of H2S was primarily initiated by the excitation of carder gas （At） through electron collisions which appeared to be the rate determining step. The experiments were carded out with initial concentration of H2S varied between 5 and 25 vol% at 150 mL/min （at standard temperature and pressure） flow rate in the input power range of 0.5 to 2 W. The reaction rate model based on continuous stirred tank reactor （CSTR） model failed to explain the global kinetics of H2S decomposition, probably due to the multiple complex reactions involved in H2S decomposition, whereas Michaelis-Menten model was satisfactory. Typical results indicated that the reaction order approached zero with increasing inlet concentration.

Hydrogen sulfide intervention in focal cerebral ischemia/reperfusion injury in rats

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.

Biological removal of air loaded with a hydrogen sulfide and ammonia mixture

The nuisance impact of air pollutant emissions from wastewater pumping stations is a major issue of concern to China. Hydrogen sulfide and ammonia are commonly the primary odor and are important targets for removal. An alternative control technology, biofiltration, was studied. The aim of this study is to investigate the potential of unit systems packed with compost in terms of ammonia and hydrogen sulfide emissions treatment, and to establish optimal operating conditions for a full-scale conceptual design. The laboratory scale biofilter packed with compost was continuously supplied with hydrogen sulfide and ammonia gas mixtures. A volumetric load of less than 150 gH 2S/(m3·d) and 230 gNH 3/(m3·d) was applied for about fifteen weeks. Hydrogen sulfide and ammonia elimination occurred in the biofilter simultaneously. The removal efficiency, removal capacity and removal kinetics in the biofilter were studied. The hydrogen sulfide removal efficiency reached was very high above 99%, and ammonia removal efficiency was about 80%. Hydrogen sulfide was oxidized into sulphate. The ammonia oxidation products were nitrite and nitrate. Ammonia in the biofilter was mainly removed by adsorption onto the carrier material and by absorption into the water fraction of the carrier material. High percentages of hydrogen sulfide or ammonia were oxidized in the first section of the column. Through kinetics analysis, the presence of ammonia did not hinder the hydrogen sulfide removal. According to the relationship between pressure drop and gas velocity for the biofilter and Reynolds number, non-Darcy flow can be assumed to represent the flow in the medium.

Exogenous Hydrogen Sulfide Enhanced Antioxidant Capacity, Amylase Activities and Salt Tolerance of Cucumber Hypocotyls and Radicles

In the present experiment, effects of sodium hydrosulfide （NariS）, a H2S donor, on the oxidative damage, antioxidant capacity and the growth of cucumber hypocotyls and radicles were studied under 100 mmol L^-1 NaCl stress. NaCl treatment significantly induced accumulation of H2O2 and thiobarbituric acid-reactive substances （TBARS） in cucumber hypocotyls and radicles, and application of NariS dramatically reduced the accumulation of H/O2 and lipid peroxidation. However, the alleviating effects greatly depended on the concentrations of NariS, and 400 ~tmol L-1 NariS treatment showed the most significant effects. Corresponding to the change of lipid peroxidation, higher activities of antioxidant enzymes as well as the antioxidant capacity indicated as DPPH scavenging ac＇tivity, chelating activity of ferrous ions and hydroxyl radical （.OH） scavenging activity were induced by Naris treatment under NaCI stress, especially by 400 Ixmol L-I Naris treatment. With the alleviating lipid peroxidation, the amylase activities in cotyledons were increased, and the length of cucumber hypocotyls and radicles were significantly promoted by NariS treatment under NaCI stress. Unlike the effects of NariS, pretreatment with other sodium salts including Na2S, NazSO4, NaHSO4, Na2SO3, NaHSO3 and NaAc did not show significant effects on the growth of cucumber hypocotyls and radicles. These salts do not release H2S. Based on above results, it can be concluded that the effects of NariS in the experiment depended on the H2S rather than other compounds derived from NariS, and the alleviating effects might related with its function in modulating antioxidant capacity and amylase activities.

Hydrogen sulfide enhances adult neurogenesis in a mouse model of Parkinson's disease

Hydrogen sulfide(H_2S) is regarded to be a protectant against diseases of the central nervous system and cardiovascular system.However, the mechanism by which H_2S elicits neuroprotective effects in the progression of Parkinson's disease(PD) remains unclear.To investigate the role of H_2S in delaying the pathological process of PD, we used the most common sodium hydrosulfide(Na HS) as an H_2S donor and established a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid(MPTP/p) in the present study.Our results show that H_2S reduced neuronal loss during the progression of PD.Notably, we found that H_2S exhibited protective effects on dopaminergic neurons.Excitingly, H_2S also increased the proliferation of neural stem cells in the subventricular zone.Next, we evaluated whether the neuroprotective effects of H_2S on dopaminergic neurons in PD are dependent on adult nerve regeneration by treating primary adult neural stem cells cultured ex vivo with 1-methyl-4-phenylpyridine.Our results show that H_2S could prevent nerve injury induced by 1-methyl-4-phenylpyridine, promote the growth of neurospheres, and promote neurogenesis by regulating Akt/glycogen synthase kinase-3β/β-catenin pathways in adult neural stem cells.These findings confirm that H_2S can increase neurogenesis in an adult mouse model of PD by regulating the Akt/glycogen synthase kinase-3β/β-catenin signaling pathway.This study was approved by the Animal Care and Use Committee of Nanjing Medical University, China(IACUC Approval No.1601153-3).

Ligliptin for treatment of type 2 diabetes mellitus with early renal injury: Efficacy and impact on endogenous hydrogen sulfide and endothelial function

BACKGROUND Diabetes is a clinically common chronic disease,and its incidence has been increasing in recent years.Diabetes is believed to accelerate the process of atherosclerosis in patients,and abnormal endothelial function is an important factor leading to diabetic kidney damage.AIM To investigate the efficacy of ligliptin in the treatment of type 2 diabetes mellitus(T2DM)with early renal injury and its effect on serum endogenous hydrogen sulfide(H2S),endothelial cell particles,and endothelial function.METHODS From January 2018 to April 2019,110 patients with T2DM and early kidney injury treated at our hospital were divided into an observation group(receiving ligliptin treatment,n=54)and a control group(receiving gliquidone therapy,n=56).Blood glucose and renal function before and after treatment were compared between the two groups.RESULTS The differences in fasting blood glucose,2 h blood glucose,and glycated hemoglobin were not statistically significant between the two groups after treatment.The urinary albumin excretion rate after treatment in the ligliptin group was 70.32±11.21μg/min,which was significantly lower than that of the gliquidone group(P=0.000).Serum endogenous H2S and endothelial cell microparticles of the ligliptin treatment group were 40.04±8.82 mol/L and 133.40±34.39,respectively,which were significantly lower than those of the gliquidone treatment group(P=0.000 for both);endothelin-dependent diastolic function and nitric oxide after treatment in the ligliptin group were 7.98%±1.22%and 190.78±30.32 mol/L,significantly higher than those of the gliquidone treatment group(P=0.000 for both).CONCLUSION Ligliptin treatment of T2DM with early renal injury has the same glucoselowering effect as gliquidone treatment.Ligliptin treatment has a better effect and it can significantly improve the renal function and vascular endothelial function of patients,and reduce serum endogenous H2S and endothelial cell particle levels.

A hypothesis for treating inflammation and oxidative stress with hydrogen sulfide during age-related macular degeneration

Age-related macular degeneration（AMD） is a leading cause of blindness and is becoming a global crisis since affected people will increase to 288 million by 2040.Genetics,age,diabetes,gender,obesity,hypertension,race,hyperopia,iris-color,smoking,sun-light and pyroptosis have varying roles in AMD,but oxidative stress-induced inflammation remains a significant driver of pathobiology.Eye is a unique organ as it contains a remarkable oxygengradient that generates reactive oxygen species（ROS） which upregulates inflammatory pathways.ROS becomes a source of functional and morphological impairments in retinal pigment epithelium（RPE）,endothelial cells and retinal ganglion cells.Reports demonstrated that hydrogen sulfide（H2S） acts as a signaling molecule and that it may treat ailments.Therefore,we propose a novel hypothesis that H2S may restore homeostasis in the eyes thereby reducing damage caused by oxidative injury and inflammation.Since H_2S has been shown to be a powerful antioxidant because of its free-radicals＇ inhibition properties in addition to its beneficial effects in age-relatedconditions,therefore,patients may benefit from H2S salubrious effects not only by minimizing their oxidant and inflammatory injuries to retina but also by lowering retinal glutamate excitotoxicity.

Facile In Situ Fabrication of Nanostructured Graphene–CuO Hybrid with Hydrogen Sulfide Removal Capacity

A simple and scalable synthetic approach for one-step synthesis of graphene–Cu O(TRGC) nanocomposite by an in situ thermo-annealing method has been developed.Using graphene oxide(GO) and copper hydroxide as a precursors reagent,the reduction of GO and the uniform deposition of in situ formed Cu O nanoparticles on graphene was simultaneously achieved.The method employed no solvents,toxic-reducing agents,or organic modifiers.The resulting nanostructured hybrid exhibited improved H2 S sorption capacity of 1.5 mmol H2S/g-sorbent(3 g S/100 g-sorbent).Due to its highly dispersed sub-20 nm Cu O nanoparticles and large specific surface area,TRGC nanocomposite exhibits tremendous potential for energy and environment applications.

Protective Effects of Hydrogen Sulfide on Portal Hypertensive Vasculopathy in Rabbits by Activating AKT-NF-κB Pathway

The role of hydrogen sulfide（H;S） in portal hypertension（PH）-induced esophagus-gastric junction vascular lesions in rabbits was observed. The rabbit PH models were established. The animals were randomly divided into the following groups: normal, PH, PH+sodium hydrosulfide（PH+S）, PH+propargylglycine（PH+PPG）. The plasma H;S levels, apoptosis of esophageal-gastric junction vascular smooth muscle cells, and the expression of nuclear transcription factor-κB（NF-κB）, p-AKT, IκBa and Bcl-2 were detected. The cystathionine γ lyase（cystathionine-gamma-splitting enzyme, CSE） in the junction vascular tissue was measured. The results showed that the plasma H;S levels and the CSE expression levels had statistically significant difference among different groups（P<0.05）. As compared with PH group, plasma H;S levels were declined obviously（11.9±4.2 vs. 20.6±4.5, P<0.05）, and CSE expression levels in the junction vascular tissue were notably reduced（1.7±0.6 vs. 2.8±0.8, P<0.05）, apoptosis rate of vascular smooth muscle cells per unit area was significantly decreased（0.10±0.15 vs. 0.24±0.07, P<0.05）, and the expression levels of p-AKT and NF-κB were significantly decreased（2.31±0.33 vs. 3.04±0.38, P<0.05; 0.33±0.17 vs. 0.51±0.23, P<0.05）, however, IκBa and Bcl-2 expression increased obviously（5.57±0.17 vs. 3.67±0.13, P<0.05; 0.79±0.29 vs. 0.44±0.36, P<0.05） in PH+PPG group. As compared with PH group, H;S levels were notably increased（32.7±7.3 vs. 20.6±4.5, P<0.05）, the CSE levels in the junction vascular tissue were significantly increased（6.3±0.7 vs. 2.8±0.8, P<0.05）, apoptosis rate of vascular smooth muscle cells per unit area was significantly increased（0.35±0.14 vs. 0.24±0.07, P<0.05）, and the expression levels of p-AKT and NF-κB were significantly increased（4.29±0.49 vs. 3.04±0.38, P<0.05; 0.77±0.27 vs. 0.51±0.23, P<0.05）, yet IκBa and Bcl-2 expression decreased significantly（3.23±0.24 vs. 3.67±0.13, P<0.05; 0.31±0.23 vs. 0.48±0.34, P<0.05） in PH+S group. It is concluded that esophagus-gastric junction vascular lesions happen under PH, and apoptosis of smooth muscle cells is declined. H;S can activate NF-κB by the p-AKT pathway, leading to the down-regulation of Bcl-2, eventually stimulating apoptosis of vascular smooth muscle cells, easing PH. H;S/CSE system may play an important role in remission of PH via the AKT-NF-κB pathway.

Hydrogen sulfide controls peripheral nerve degeneration and regeneration:a novel therapeutic strategy for peripheral demyelinating disorders or nerve degenerative diseases

After peripheral nerve injury, the process of Wallerian degeneration is initiated in the distal stump of injured nerves. Wallerian degeneration in peripheral nerves involves axonal degeneration and degradation of the myelin sheath in Schwann cells. This provides the necessary conditions for axonal regeneration and remyelination. After nerve injury, macrophages are also recruited to the distal nerve stump and, together with Schwann cells, play a role in the clearance of myelin debris.