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.

Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

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.

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.

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.

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.

Effect of Exogenous Hydrogen Sulfide(H_2S) on the Electrocardiogram(ECG) of Rats Generally Anaesthetized by Zoletil

Hydrogen sulfide （H2S） is the third gaseous signaling molecule discovered in recent years, and plays an important physiological role in the cardivascular system. To explore the effects of different doses of exogenous H2S on the electrocardiogram （ECG） of rats generally anesthetized by zoletil, different doses of NariS solution were used for the intervention of intraperitoneal injection 20 rain before the zoletil anesthesia. The ECGs of rats from each treatment group during the time range of 10^th-50^th min were determined under general anesthesia, and then were compared with those from the control group. The results showed that exogenous H2S could significantly reduce the Q-T interval time limit, thus played a role in slowing tachycardia or arrhythmia and other anomalies, thereby protecting the heart. S-T segment and T segment evaluation values were significantly reduced, which might be associated with bradycardia.

Research Development of Control Technology of Hydrogen Sulfide in Biogas Slurry

In order to provide help for the accurate application of biogas slurry in the field, the application of biogas slurry and control technology of hydrogen sulfide in biogas slurry were reviewed. Results of recent researches suggested that source control and end-treatment were the two measures to remove hydrogen sulfide in biogas slurry, including physical method, chemical method and biological method. Some conventional deodorizing methods were introduced and compared.

Reactions of Group V Metal Atoms with Hydrogen Sulfide： Argon Matrix Infrared Spectra and Theoretical Calculations

The reaction of laser-ablated vanadium, niobium and tantalum atoms with hydrogen sulfide has been investigated using matrix isolation FTIR and theoretical calculations. The metal atoms inserted into the H-S bond of H2S to form the HMSH molecules （M=V, Nb, Ta）, which rearranged to H2MS molecules on annealing for Nb and Ta. The HMSH molecule can also further react with another H2S to form the H2M（SH）2 molecules. These new molecules were identified on the basis of the D2S and H234S isotopic substitutions. DFT （B3LYP and BPW91） theoretical calculations are used to predict energies, geometries, and vibrational frequencies for these novel metal dihydrido complexes and molecules. Reaction mechanism for formation of group V dihydrido complex was investigated by DFT internal reaction coordinate calculations. The dissociation of HVSH gave VS＋H2 on broad band irradiation and reverse reaction happened on annealing. Based on B3LYP calculation releasing hydrogen from HVSH is endothermic only by 13.5 kcal/mol with lower energy barrier of 16.9 kcal/mol.

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.

Studies on the Tolerating Mechanism for Sulfide in Urechis unicinctus (Echiura: Urechidae) ──Cytological Observation on Urechis unicinctus in Different Hydrogen Sulfide Environment

This study on the cytological changes of the body wall,aspiratory intestine and crissal bursa in Urechis unicinctus by light microscope (LM) and transmission electron microscope (TEM) showed that the difference between the body wall and the natural environment rich in H 2S was not obvious; that the wall color of the aspiratory intestine in H 2S rich environment changed from normal semitransparency to dark brown; that its epithelia were disassembled and the electron density of its cytoplasm matrix was lower; and that in H 2S rich environment many basophilic granules occurred in the epithelia of the crissal bursa. Granules with single membrane and myelinefingure were found with TEM.

Bile-acid-activated farnesoid X receptor regulates hydrogen sulfide production and hepatic microcirculation

AIM: To investigate whether the farnesoid X receptor (FXR) regulates expression of liver cystathionase (CSE), a gene involved in hydrogen sulfi de (H2S) generation. METHODS: The regulation of CSE expression in response to FXR ligands was evaluated in HepG2 cells and in wild-type and FXR null mice treated with 6-ethyl chenodeoxycholic acid (6E-CDCA), a synthetic FXR ligand. The analysis demonstrated an FXR responsive element in the 5'-flanking region of the human CSE gene. The function of this site was investigated by luciferase reporter assays, chromatin immunoprecipitation and electrophoretic mobility shift assays. Livers obtained from rats treated with carbon tetrachloride alone, or in combination with 6-ethyl chenodeoxycholic acid, were studied for hydrogen sulphide generation and portal pressure measurement. RESULTS: Liver expression of CSE is regulated by bile acids by means of an FXR-mediated mechanism. Western blotting, qualitative and quantitative polymerase chain reaction, as well as immunohistochemical analysis, showed that expression of CSE in HepG2 cells and in mice is induced by treatment with an FXR ligand. Administration of 6E-CDCA to carbon tetrachloride treated rats protected against the down-regulation of CSE expression, increased H2S generation, reduced portal pressure and attenuated the endothelial dysfunction of isolated and perfused cirrhotic rat livers. CONCLUSION: These results demonstrate that CSE is an FXR-regulated gene and provide a new molecular explanation for the pathophysiology of portal hypertension.

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 attenuates gastric mucosal injury induced by restraint water-immersion stress via activation of KATPchannel and NF-κB dependent pathway

AIMTo explore the effect of hydrogen sulfide (H2S) on restraint water-immersion stress (RWIS)-induced gastric lesions in rats and the influence of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway on such an effect.METHODSMale Wistar rats were randomly divided into a control group, a physiological saline (PS) group, a sodium hydrosulfide (NaHS) group, a glibenclamide (Gl) group, Gl plus NaHS group, a pyrrolidine dithiocarbamate (PDTC) group, and a PDTC plus NaHS group. Gastric mucosal injury was induced by RWIS for 3 h in rats, and gastric mucosal damage was analyzed after that. The PS, NaHS (100 μmol/kg body weight), Gl (100 μmol/kg body weight), Gl (100 μmol/kg or 150 μmol/kg body weight) plus NaHS (100 μmol/kg body weight), PDTC (100 μmol/kg body weight), and PDTC (100 μmol/kg body weight) plus NaHS (100 μmol/kg body weight) were respectively injected intravenously before RWIS.RESULTSRWIS induced serious gastric lesions in the rats in the PS pretreatment group. The pretreatment of NaHS (a H2S donor) significantly reduced the damage induced by RWIS. The gastric protective effect of the NaHS during RWIS was attenuated by PDTC, an NF-κB inhibitor, and also by glibenclamide, an ATP-sensitive potassium channel blocker, in a dose-dependent manner.CONCLUSIONThese results suggest that exogenous H2S plays a protective role against RWIS injury in rats, possibly through modulation of KATP channel opening and the NF-κB dependent pathway.

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).

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.