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Sustained release of Hydrogen sulfide from anisotropic ferrofluid hydrogel for the repair of spinal cord injury

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Bioactive Materials 2023年第5期23卷 118-128页

作者： Ruofei Wang Xia-Xiao Wu Zhenming Tian Tian Hu Chaoyang Cai Guan-Ping Wu Gang-Biao Jiang Bin Liu Department of Spine Surgery The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou510630China Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery Guangzhou510630China Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery Guangzhou510630China Key Laboratory for Biobased Materials and Energy of Ministry of Education College of Materials and EnergySouth China Agricultural UniversityGuangzhou510642China

Spinal cord injury(SCI)results in massive neuronal death,axonal disruption,and cascading inflammatory response,which causes further damage to impaired neurons.The survived neurons with damaged function fail to form effective neuronal circuits.It is mainly caused by the neuroinflammatory microenvironment at injury sites and regenerated axons without guidance.To address this challenge,a ferrofluid hydrogel(FFH)was prepared with Ferric tetrasulfide(Fe3S4),carboxymethyl chitosan,and gold.Its internal structural particles can be oriented in a magnetic field to acquire anisotropy.Moreover,Fe3S4 can release Hydrogen sulfide(H2S)with anti-inflammatory effects under acidic conditions.Regarding in vitro experiments,0.01g/ml Fe3S4 FFH significantly reduced the inflammatory factors produced by LPS-induced BV2 cells.Oriented and longer axons of the induced neural stem cells loaded on anisotropic FFH were observed.In vivo experiments showed that FFH reduced the activated microglia/macrophage and the expression of pro-inflammatory factors in SCI rats through the NF-κB pathway.Moreover,it significantly promoted directional axonal regrowth and functional recovery after SCI.Given the critical role of inhibition of neuroinflammation and directional axonal growth,anisotropic Fe3S4 FFH is a promising alternative for the treatment of SCI.

关键词： Spinal cord injury Anisotropic Ferrofluid Hydrogen sulfide

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

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 1-17页

作者： Jiafeng Zou Zeting Yuan Xiaojie Chen You Chen Min Yao Yang Chen Xiang Li Yi Chen Wenxing Ding Chuanhe Xia Yuzheng Zhao Feng Gao Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism School of PharmacyEast China University of Science and TechnologyShanghai 200237China Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou 310053China Shanghai Key Laboratory of Functional Materials Chemistry East China University of Science and TechnologyShanghai 200237China Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science and TechnologyShanghai 200237China Optogenetics and Synthetic Biology Interdisciplinary Research Center State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghai 200237China CAS Center for Excellence in Brain Science Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Research Unit of New Techniques for Live-cell Metabolic Imaging Chinese Academy of Medical SciencesBeijing 100050China

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.

关键词： Hydrogen sulfide Disease mechanisms Removal of Hydrogen sulfide Responsive nanoplatforms Challenges Biomedical applications

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

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中国化学工程学报:英文版 2023年第7期59卷 210-221页

作者： Zhonghao Li Yuanyuan Yang Huanong Cheng Yun Teng Chao Li Kangkang Li Zhou Feng Hongwei Jin Xinshun Tan Shiqing Zheng College of Chemical Engineering Qingdao University of Science and TechnologyQingdao 266042China

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.

关键词： Ionic liquids Hydrogen sulfide Solubility Henry's constant Chemical reaction equilibrium constant Model

Recent advances of small-molecule fluorescent probes for detecting biological Hydrogen sulfide

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Frontiers of Chemical Science and Engineering 2022年第1期16卷 34-63页

作者： Lei Zhou Yu Chen Baihao Shao Juan Cheng Xin Li Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals Zhejiang University of TechnologyHangzhou 310014China College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China

H_(2)S is well-known as a colorless,acidic gas,with a notoriously rotten-egg smell.It was recently revealed that H_(2)S is also an endogenous signaling molecule that has important biological functions,however,most of its physiology and pathology remains elusive.Therefore,the enthusiasm for H_(2)S research remains.Fluorescence imaging technology is an important tool for H_(2)S biology research.The development of fluorescence imaging technology has realized the study of H_(2)S in subcellular organelles,facilitated by the development of fluorescent probes.The probes reviewed in this paper were categorized according to their chemical mechanism of sensing and were divided into three groups:H_(2)S reducibility-based probes,H_(2)S nucleophilicity-based probes,and metal sulfide precipitation-based probes.The structure of the probes,their sensing mechanism,and imaging results have been discussed in detail.Moreover,we also introduced some probes for hydrogen polysulfides.

关键词： Hydrogen sulfide fluorescent probe reducibility nucleophilicity copper sulfide precipitate hydrogen polysulfides

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

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World Journal of Gastroenterology 2023年第29期29卷 4557-4570页

作者： Hong-Zhao Sun Chen-Yu Li Yuan Shi Jin-Jin Li Yi-Ya Wang Li-Na Han Lu-Jie Zhu Ya-Fei Zhang College of Life Science Qi Lu Normal UniversityZhangqiu 250200Shandong ProvinceChina

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(P0.05).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.

关键词： Nucleus tractus solitarius Hydrogen sulfide Gastric motility Nuclear factor kappa-B Transient receptor potential vanilloid 1

Focal adhesion kinase signaling is necessary for the Hydrogen sulfide-enhanced proliferation,migration,and invasion of HTR8/SVneo human trophoblasts

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Reproductive and Developmental Medicine 2023年第2期7卷 75-82页

作者： Xian-Li Wang Jing Tang Department of Pharmacy Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China

Objective:Hydrogen sulfide(H_(2)S)has been elucidated that it promotes migration and invasion in human placenta trophoblasts.However,the signaling pathway underlying H_(2)S-based regulation of trophoblasts remains unknown.Hence,we investigated the potential effect of sodium hydrosulfide(NaHS),an exogenous H_(2)S donor,on extravillous trophoblasts.Methods:The Cell Counting Kit-8 was used to detect the proliferative activity of trophoblasts and to screen the optimal concentration of NaHS.The migration and invasion of HTR8/SVneo cells were measured by Transwell assays.Gene expression was determined by quantitative real-time PCR analysis.Protein expression was determined by western blot.Results:We found that NaHS could promote the proliferation,migration,and invasion of HTR8/SVneo cells.The phosphorylation of focal adhesion kinase(FAK),Src,and extracellular signal-regulated kinase(ERK)were activated by NaHS.Moreover,NaHS also upregulated the expression of matrix metalloproteinase-2(MMP-2)and MMP-9,downregulated the expression of E-cadherin in HTR8/SVneo cells.The application of NaHS could increase the expression of cystathionine-β-synthase.Conclusion:Both FAK-Src signaling and the upstream signaling cascade of ERK activation play a significant important role in NaHS-induced proliferation,migration,and invasion via upregulating activity of MMP-2,MMP-9,and downregulating E-cadherin in HTR8/SVneo cells.These novel findings may provide a strong foundation for the clinical application of H_(2)S donor drugs.

关键词： Hydrogen sulfide Trophoblast Proliferation Migration Invasion Focal adhesion kinase signaling

Hydrogen sulfide, a signaling molecule in plant stress responses

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Journal of Integrative Plant Biology 2021年第1期63卷 146-160页

作者： Jing Zhang Mingjian Zhou Heng Zhou Didi Zhao Cecilia Gotor Luis CRomero Jie Shen Zhenglin Ge Zhirong Zhang Wenbiao Shen Xingxing Yuan Yanjie Xie Laboratory Center of Life Sciences College of Life SciencesNanjing Agricultural UniversityNanjing 210095China Instituto de Bioquimica Vegetal y Fotosintesis Consejo Superior de Investigaciones Cientfficas y Universidad de SevillaSevilla 41092Spain Institute of Industrial Crops Jiangsu Academy of Agricultural SciencesNanjing 210014China

Gaseous molecules, such as Hydrogen sulfide(H_2S)and nitric oxide(NO), are crucial players in cellular and(patho)physiological processes in biological systems. The biological functions of these gaseous molecules, which were first discovered and identified as gasotransmitters in animals, have received unprecedented attention from plant scientists in recent decades. Researchers have arrived at the consensus that H_2S is synthesized endogenously and serves as a signaling molecule throughout the plant life cycle.However, the mechanisms of H_2S action in redox biology is still largely unexplored. This review highlights what we currently know about the characteristics and biosynthesis of H_2S in plants. Additionally,we summarize the role of H_2S in plant resistance to abiotic stress. Moreover, we propose and discuss possible redox-dependent mechanisms by which H_2S regulates plant physiology.

关键词： gasotransmitter Hydrogen sulfide persulfidation plant physiology redox signaling stress response

Hydrogen sulfide-linked persulfidation of ABI4 controls ABA responses through the transactivation of MAPKKK18 in Arabidopsis

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Molecular Plant 2021年第6期14卷 921-936页

作者： Mingjian Zhou Jing Zhang Jie Shen Heng Zhou Didi Zhao Cecilia Gotor Luis CRomero Ling Fu Zongmin Li Jing Yang Wenbiao Shen Xingxing Yuan Yanjie Xie Laboratory Center of Life Sciences College of Life SciencesNanjing Agricultural UniversityNanjing 210095PR China Instituto de Bioquímica Vegetal y Fotosíntesis Consejo Superior de Investigaciones Científicas y Universidad de SevillaAvenida Américo Vespucio 4941092 SevillaSpain State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences BeijingBeijing Institute of LifeomicsBeijing 102206China Institute of Industrial Crops Jiangsu Academy of Agricultural SciencesNanjing 210014China

Hydrogen sulfide(H2S)is a signaling molecule that regulates plant hormone and stress responses.The phytohormone abscisic acid(ABA)plays an important role in plant adaptation to unfavorable environmental conditions and induces the persulfidation of L-CYSTEINE DESULFHYDRASE1(DES1)and the production of H2S in guard cells.However,it remains largely unclear how H2S and protein persulfidation participate in the relay of ABA signals.In this study,we discovered that ABSCISIC ACID INSENSITIVE 4(ABI4)acts downstream of DES1 in the control of ABA responses in Arabidopsis.ABI4 undergoes persulfidation at Cys250 that is triggered in a time-dependent manner by ABA,and loss of DES1 function impairs this process.Cys250 and its persulfidation are essential for ABI4 function in the regulation of plant responses to ABA and the H2S donor NaHS during germination,seedling establishment,and stomatal closure,which are abolished in the ABI4Cys250Ala mutated variant.Introduction of the ABI4Cys250Ala variant into the abi4 des1 mutant did not rescue its hyposensitivity to ABA.Cys250 is critical for the binding of ABI4 to its cognate motif in the promoter of Mitogen-Activated Protein Kinase Kinase Kinase 18(MAPKKK18),which propagates the MAPK signaling cascade induced by ABA.Furthermore,the DES1-mediated persulfidation of ABI4 enhances the transactivation activity of ABI4 toward MAPKKK18,and ABI4 can bind the DES1 promoter,forming a regulatory loop.Taken together,these findings advance our understanding of a post-translational regulatory mechanism and suggest that ABI4 functions as an integrator of ABA and MAPK signals through a process in which DES1-produced H2S persulfidates ABI4 at Cys250.

关键词： Hydrogen sulfide persulfidation DES1 ABI4 MAPKXK18 transactivation ABA response

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

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Neural Regeneration Research 2021年第7期16卷 1353-1358页

作者： Min Wang Juan-Juan Tang Lin-Xiao Wang Jun Yu Li Zhang Chen Qiao Department of Clinical Pharmacy The Affiliated Hospital of Jiangsu UniversityJiangsu UniversityZhenjiangJiangsu ProvinceChina Department of Geriatrics Affiliated Brain Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina School of Medicine&Holistic Integrative Medicine Nanjing University of Chinese MedicineNanjingJiangsu ProvinceChina Laboratory of Neurological Diseases Department of Neurologythe Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical UniversityChangzhouJiangsu ProvinceChina Laboratory of Reproductive Medicine The Affiliated Hospital of Jiangsu UniversityJiangsu UniversityZhenjiangJiangsu ProvinceChina

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).

关键词： factor Hydrogen sulfide medical gas neural stem cells neurogenesis neuroprotection Parkinson's disease pathways