With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic...With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.展开更多
During wet complexation denitrification of flue gas,Fe^(Ⅱ)EDTA regeneration,also known as reducing Fe^(Ⅱ)EDTA and Fe^(Ⅱ)EDTA-nitric oxide(NO)to Fe^(Ⅱ)EDTA,is crucial.In this paper,ultraviolet(UV)light was used for...During wet complexation denitrification of flue gas,Fe^(Ⅱ)EDTA regeneration,also known as reducing Fe^(Ⅱ)EDTA and Fe^(Ⅱ)EDTA-nitric oxide(NO)to Fe^(Ⅱ)EDTA,is crucial.In this paper,ultraviolet(UV)light was used for the first time to reduce Fe^(Ⅱ)EDTA-NO.The experimental result demonstrated that Fe^(Ⅱ)EDTA-NO reduction rate increased with UV power increasing,elevated temperature,and initial Fe^(Ⅱ)EDTA-NO concentration decreasing.Fe^(Ⅱ)EDTA-NO reduction rate increased first and then decreased as pH value increased(2.0-10.0).Fe^(Ⅱ)EDTA-NO reduction with UV irradiation presented a first order reaction with respect to Fe^(Ⅱ)EDTA-NO.Compared with other Fe^(Ⅱ)EDTA regeneration methods,Fe^(Ⅱ)EDTA regeneration with UV show more superiority through comprehensive consideration of regeneration rate and procedure.Subsequently,NO absorption experiment by Fe^(Ⅱ)EDTA solution with UV irradiation confirmed that UV can significantly promote the NO removal performance of Fe^(Ⅱ)EDTA.Appropriate oxygen concentration(3%(vol))and acidic environment(pH=4)was favorable for NO removal.With UV power increasing as well as temperature decreasing,NO removal efficiency rose.In addition,the mechanism research indicates that NO from flue gas is mostly converted to NO_(2)-,NO_(3)-,NH_(4)^(+),N_(2),and N_(2)O with Fe^(Ⅱ)EDTA absorption liquid with UV irradiation.UV strengthens NO removal in Fe^(Ⅱ)EDTA absorption liquid by forming a synergistic effect of oxidation-reduction-complexation.Finally,compared with NO removal methods with Fe^(Ⅱ)EDTA,Fe^(Ⅱ)EDTA combined UV system shows prominent technology advantage in terms of economy and secondary pollution.展开更多
Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to expl...Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.展开更多
The hydrothermal synthesis of In_(2)O_(3)and CeO_(2)–In_(2)O_(3)is investigated as well as the properties of sensor layers based on these compounds.During the synthesis of In_(2)O_(3),intermediate products In(OH)_(3)...The hydrothermal synthesis of In_(2)O_(3)and CeO_(2)–In_(2)O_(3)is investigated as well as the properties of sensor layers based on these compounds.During the synthesis of In_(2)O_(3),intermediate products In(OH)_(3)and InOOH are formed,which are the precursors of stable cubic(c-In_(2)O_(3))and metastable rhombohedral(rh-In_(2)O_(3))phases,respectively.A transition from c-In_(2)O_(3)to rh-In_(2)O_(3)is observed with the addition of CeO_(2).The introduction of cerium into rh-In_(2)O_(3)results in a decrease in the sensor response to hydrogen,while it increases in composites based on c-In_(2)O_(3).The data on the sensor activity of the composites correlate with XPS results in which CeO_(2)causes a decrease in the concentrations of chemisorbed oxygen and oxygen vacancies in rh-In_(2)O_(3).The reverse situation is observed in composites based on c-In_(2)O_(3).Compared to In_(2)O_(3)and CeO_(2)–In_(2)O_(3)obtained by other methods,the synthesized composites demonstrate maximum response to H_(2)at low temperatures by 70–100℃,and have short response time(0.2–0.5 s),short recovery time(6–7 s),and long-term stability.A model is proposed for the dependence of sensitivity on the direction of electron transfer between In_(2)O_(3)and CeO_(2).展开更多
Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in mo...Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in modulating the plant’s response to iron deficiency.Iron deficiency leads to an increase in the activity of heme oxygenase(HO)and the subsequent generation of CO.Additionally,it alters the polar subcellular distribution of Pin-Formed 1(PIN1)proteins,resulting in enhanced auxin transport.This alteration,in turn,leads to an increase in NO accumulation.Furthermore,iron deficiency enhances the activity of ferric chelate reductase(FCR),as well as the expression of the Fer-like iron deficiency-induced transcription factor 1(FIT)and the ferric reduction oxidase 2(FRO2)genes in plant roots.Overexpression of the long hypocotyl 1(HY1)gene,which encodes heme oxygenase,or the CO donor treatment resulted in enhanced basipetal auxin transport,higher FCR activity,and the expression of FIT and FRO2 genes under Fe deficiency.Here,a potential mechanism is proposed:CO and NO interact with auxin to address iron deficiency stress.CO alters auxin transport,enhancing its accumulation in roots and up-regulating key iron-related genes like FRO2 and IRT1.Elevated auxin levels affect NO signaling,leading to greater sensitivity in root development.This interplay promotes FCR activity,which is crucial for iron absorption.Together,these molecules enhance iron uptake and root growth,revealing a novel aspect of plant physiology in adapting to environmental stress.展开更多
BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as com...BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as complications and adverse outcomes persist.Incorporating humanized nursing modes and novel treatments like nitric oxide inhalation may enhance recovery and reduce postoperative complications.AIM To evaluate the effects of a humanized nursing mode combined with nitric oxide inhalation on the rehabilitation outcomes of patients undergoing lung surgery,focusing on pulmonary function,recovery speed,and overall treatment costs.METHODS A total of 79 patients who underwent lung surgery at a tertiary hospital from March 2021 to December 2021 were divided into a control group(n=39)receiving a routine nursing program and an experimental group(n=40)receiving additional humanized nursing interventions and atomized inhalation of nitric oxide.Key indicators were compared between the two groups alongside an analysis of treatment costs.RESULTS The experimental group demonstrated significant improvements in pulmonary function,reduced average recovery time,and lower total treatment costs compared to the control group.Moreover,the quality of life in the experimental group was significantly better in the 3 months post-surgery,indicating a more effective rehabilitation process.CONCLUSION The combination of humanized nursing mode and nitric oxide inhalation in postoperative care for lung surgery patients significantly enhances pulmonary rehabilitation outcomes,accelerates recovery,and reduces economic burden.This approach offers a promising reference for improving patient care and rehabilitation efficiency following lung surgery.展开更多
Advancements in sensor technology have significantly enhanced atmospheric monitoring.Notably,metal oxide and carbon(MO_(x)/C)hybrids have gained attention for their exceptional sensitivity and room-temperature sensing...Advancements in sensor technology have significantly enhanced atmospheric monitoring.Notably,metal oxide and carbon(MO_(x)/C)hybrids have gained attention for their exceptional sensitivity and room-temperature sensing performance.However,previous methods of synthesizing MO_(x)/C composites suffer from problems,including inhomogeneity,aggregation,and challenges in micropatterning.Herein,we introduce a refined method that employs a metal–organic framework(MOF)as a precursor combined with direct laser writing.The inherent structure of MOFs ensures a uniform distribution of metal ions and organic linkers,yielding homogeneous MO_(x)/C structures.The laser processing facilitates precise micropatterning(<2μm,comparable to typical photolithography)of the MO_(x)/C crystals.The optimized MOF-derived MO_(x)/C sensor rapidly detected ethanol gas even at room temperature(105 and 18 s for response and recovery,respectively),with a broad range of sensing performance from 170 to 3,400 ppm and a high response value of up to 3,500%.Additionally,this sensor exhibited enhanced stability and thermal resilience compared to previous MOF-based counterparts.This research opens up promising avenues for practical applications in MOF-derived sensing devices.展开更多
Highly sensitive gas sensors with remarkably low detection limits are attractive for diverse practical application fields including real-time environmental monitoring,exhaled breath diagnosis,and food freshness analys...Highly sensitive gas sensors with remarkably low detection limits are attractive for diverse practical application fields including real-time environmental monitoring,exhaled breath diagnosis,and food freshness analysis.Among various chemiresistive sensing materials,noble metal-decorated semiconducting metal oxides(SMOs)have currently aroused extensive attention by virtue of the unique electronic and catalytic properties of noble metals.This review highlights the research progress on the designs and applications of different noble metal-decorated SMOs with diverse nanostructures(e.g.,nanoparticles,nanowires,nanorods,nanosheets,nanoflowers,and microspheres)for high-performance gas sensors with higher response,faster response/recovery speed,lower operating temperature,and ultra-low detection limits.The key topics include Pt,Pd,Au,other noble metals(e.g.,Ag,Ru,and Rh.),and bimetals-decorated SMOs containing ZnO,SnO_(2),WO_(3),other SMOs(e.g.,In_(2)O_(3),Fe_(2)O_(3),and CuO),and heterostructured SMOs.In addition to conventional devices,the innovative applications like photo-assisted room temperature gas sensors and mechanically flexible smart wearable devices are also discussed.Moreover,the relevant mechanisms for the sensing performance improvement caused by noble metal decoration,including the electronic sensitization effect and the chemical sensitization effect,have also been summarized in detail.Finally,major challenges and future perspectives towards noble metal-decorated SMOs-based chemiresistive gas sensors are proposed.展开更多
Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the ...Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain, including neuropathic pain, bone cancer pain, inflammatory pain, and morphine tolerance. The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase, which leads to subsequent production of cGMP. cGMP then activates cGMP-dependent protein kinase(PKG), resulting in the activation of multiple targets such as the opening of ATP-sensitive K+ channels. The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules, as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain. In dorsal root ganglion neurons, natriuretic peptide binds to particulate guanylyl cyclase, generating and further activating the cGMP/PKG pathway, and it also contributes to the development of chronic pain. Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models. Notably the NO/cGMP signaling pathway induces expression of downstream effectors, exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain. These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain, and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy.展开更多
Dysfunction of neuronal nitric oxide synthase contributes to neurotoxicity,which triggers cell death in various neuropathological diseases,including epilepsy.Studies have shown that inhibition of neuronal nitric oxide...Dysfunction of neuronal nitric oxide synthase contributes to neurotoxicity,which triggers cell death in various neuropathological diseases,including epilepsy.Studies have shown that inhibition of neuronal nitric oxide synthase activity increases the epilepsy threshold,that is,has an anticonvulsant effect.However,the exact role and potential mechanism of neuronal nitric oxide synthase in seizures are still unclear.In this study,we performed RNA sequencing,functional enrichment analysis,and weighted gene coexpression network analysis of the hippocampus of tremor rats,a rat model of genetic epilepsy.We found damaged hippocampal mitochondria and abnormal succinate dehydrogenase level and Na+-K+-ATPase activity.In addition,we used a pilocarpine-induced N2a cell model to mimic epileptic injury.After application of neuronal nitric oxide synthase inhibitor 7-nitroindazole,changes in malondialdehyde,lactate dehydrogenase and superoxide dismutase,which are associated with oxidative stress,were reversed,and the increase in reactive oxygen species level was reversed by 7-nitroindazole or reactive oxygen species inhibitor N-acetylcysteine.Application of 7-nitroindazole or N-acetylcysteine downregulated the expression of caspase-3 and cytochrome c and reversed the apoptosis of epileptic cells.Furthermore,7-nitroindazole or N-acetylcysteine downregulated the abnormally high expression of NLRP3,gasdermin-D,interleukin-1βand interleukin-18.This indicated that 7-nitroindazole and N-acetylcysteine each reversed epileptic cell death.Taken together,our findings suggest that the neuronal nitric oxide synthase/reactive oxygen species pathway is involved in pyroptosis of epileptic cells,and inhibiting neuronal nitric oxide synthase activity or its induced oxidative stress may play a neuroprotective role in epilepsy.展开更多
Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of a...Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of angiogenesis during the regeneration process,we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells,thereby promoting microvascular regeneration in aged mice after spinal cord injury.In this study,we established young and aged mouse models of contusive spinal cord injury using a modified Allen method.We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord.Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro.Furthermore,intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord,thereby improving neurological function.The role of metformin was reversed by compound C,an adenosine monophosphate-activated protein kinase inhibitor,both in vivo and in vitro,suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury.These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway,thereby improving the neurological function of aged mice after spinal cord injury.展开更多
Background:Zataria multiflora and carvacrol showed various pharmacological prop-erties including anti-inflammatory and anti-oxidant effects.However,up to now no studies have explored its potential benefits in ameliora...Background:Zataria multiflora and carvacrol showed various pharmacological prop-erties including anti-inflammatory and anti-oxidant effects.However,up to now no studies have explored its potential benefits in ameliorating sepsis-induced aortic and cardiac injury.Thus,this study aimed to investigate the effects of Z.multiflora and carvacrol on nitric oxide(NO)and oxidative stress indicators in lipopolysaccharide(LPS)-induced aortic and cardiac injury.Methods:Adult male Wistar rats were assigned to:Control,lipopolysaccharide(LPS)(1 mg/kg,intraperitoneal(i.p.)),and Z.multiflora hydro-ethanolic extract(ZME,50–200 mg/kg,oral)-and carvacrol(25–100 mg/kg,oral)-treated groups.LPS was in-jected daily for 14 days.Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration.At the end of the study,the levels of malondialdehyde(MDA),NO,thiols,and antioxidant enzymes were evaluated.Results:Our findings showed a significant reduction in the levels of superoxide dis-mutase(SOD),catalase(CAT),and thiols in the LPS group,which were restored by ZME and carvacrol.Furthermore,ZME and carvacrol decreased MDA and NO in car-diac and aortic tissues of LPS-injected rats.Conclusions:The results suggest protective effects of ZME and carvacrol on LPS-induced cardiovascular injury via improved redox hemostasis and attenuated NO pro-duction.However,additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.展开更多
Chinese tonifying herbs, which are classified into four functional categories (namely, Yang, Qi, Yin, Blood) are commonly used for restoring normal body function and the prevention of diseases. To explore cell-based b...Chinese tonifying herbs, which are classified into four functional categories (namely, Yang, Qi, Yin, Blood) are commonly used for restoring normal body function and the prevention of diseases. To explore cell-based biological markers for Blood-enriching Chinese herbs, we investigate the effect of 11 commonly used Blood-enriching herbs on erythropoietin (EPO) production in HepG2 cells. Herbs for nourishing Yin were tested for determining the specificity of Blood-enriching herbs in inducing EPO production. In addition, the effects of Blood-enriching herbs on nitric oxide (NO) production in both HepG2 cells and human umbilical vein endothelial cells (HUVECs) were also investigated. The results indicated that methanolic extracts of Blood-enriching herbs (but not Yin-nourishing herbs) showed characteristic pharmacological activity in inducing EPO production in HepG2 cells and NO release in HUVECs. The experimental findings, therefore, support the use of cell-based EPO production and NO release as biological markers for Blood-enriching Chinese tonifying herbs.展开更多
BACKGROUND Although the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)induces more rapid liver regeneration than portal vein embolization,the mechanism remains unclear.AIM To assess...BACKGROUND Although the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)induces more rapid liver regeneration than portal vein embolization,the mechanism remains unclear.AIM To assess the influence of inflammatory cytokines and endothelial nitric oxide synthase(eNOS)activation on liver regeneration in ALPPS.METHODS The future liver remnant/body weight(FLR/BW)ratio,hepatocyte proliferation,inflammatory cytokine expression,and activation of the Akt-eNOS pathway were evaluated in rat ALPPS and portal vein ligation(PVL)models.Hepatocyte proliferation was assessed based on Ki-67 expression,which was confirmed using immunohistochemistry.The serum concentrations of inflammatory cytokines were measured using enzyme linked immune-solvent assays.The Akt-eNOS pathway was assessed using western blotting.To explore the role of inflammatory cytokines and NO,Kupffer cell inhibitor gadolinium chloride(GdCl3),NOS inhibitor N-nitro-arginine methyl ester(L-NAME),and NO enhancer molsidomine were administered intraperitoneally.RESULTS The ALPPS group showed significant FLR regeneration(FLR/BW:1.60%±0.08%,P<0.05)compared with that observed in the PVL group(1.33%±0.11%)48 h after surgery.In the ALPPS group,serum interleukin-6 expression was suppressed using GdCl3 to the same extent as that in the PVL group.However,the FLR/BW ratio and Ki-67 labeling index were significantly higher in the ALPPS group administered GdCl3(1.72%±0.19%,P<0.05;22.25%±1.30%,P<0.05)than in the PVL group(1.33%±0.11%and 12.78%±1.55%,respectively).Phospho-Akt Ser473 and phospho-eNOS Ser1177 levels were enhanced in the ALPPS group compared with those in the PVL group.There was no difference between the ALPPS group treated with L-NAME and the PVL group in the FLR/BW ratio and Ki-67 labeling index.In the PVL group treated with molsidomine,the FLR/BW ratio and Ki-67 labeling index increased to the same level as in the ALPPS group.CONCLUSION Early induction of inflammatory cytokines may not be pivotal for accelerated FLR regeneration after ALPPS,whereas Akt-eNOS pathway activation may contribute to accelerated regeneration of the FLR.展开更多
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(N...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.展开更多
BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is bei...BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.展开更多
Neuronal nitric oxide synthase(nNOS)was the producer of nitric oxide(NO)which played important gas messenger molecules in biological process.It also can take effect as immune regulation molecule in organism.Black rock...Neuronal nitric oxide synthase(nNOS)was the producer of nitric oxide(NO)which played important gas messenger molecules in biological process.It also can take effect as immune regulation molecule in organism.Black rockfish(Sebastes schlegelii)is an important economic fish which were widely farmed in East Asia countries.Meanwhile,the pathogenic bacteria such as the Edwardsiella tarda and Vibrio anguillarum in seawater always brought serious obstacles to their healthy growth.In order to explore the expression pattern of n NOS gene under the pathogen stimulation and predict its immune function,the n NOS gene in black rockfish named Ssn NOS was identified.It was 3780 bp in length,located on chromosome 6,and contained 27 coding domain sequence(CDs).According to the phylogenetic analysis,the Ssn NOS showed closest relative to the counterpart gene of swamp eel(Monopterus albus).Meanwhile,analysis of Ssn NOS expression in various healthy tissues showed that Ssn NOS expression level was highest in healthy brain tissues,followed by intestinal tissues.In addition,Ssn NOS showed significant expression changes in response to stimulation by two pathogens.Particular in gill,the expression of Ssn NOS after pathogenic stimulation increased significantly.The Elisa analysis showed the Ssn NOS content in gills was much higher than that in other tissues at all time points.Moreover,the expression patterns of Ssn NOS in brain,intestine and kidney after stimulation by pathogens showed a distinct expression pattern which first down-regulated and then up-regulated.Therefore,the Ssn NOS may be an important signaling molecule for fish to respond rapidly in immune stimulation.展开更多
Magnesium-based biodegradable metals as cardiovascular stents have shown a lot of excellent performance, which have been used to treat coronary artery diseases. However, the excessive degradation rate, imperfect bioco...Magnesium-based biodegradable metals as cardiovascular stents have shown a lot of excellent performance, which have been used to treat coronary artery diseases. However, the excessive degradation rate, imperfect biocompatibility and delayed re-endothelialization still lead to a considerable challenge for its application. In this work, to overcome these shortcomings, a compound of catalyzing nitric oxide(NO) generation containing copper ions(Cu^(2+)) and hyaluronic acid(HA), an important component of the extracellular matrix, were covalently immobilized on a hydrofluoric acid(HF)-pretreated ZE21B alloy via amination layer for improving its corrosion resistance and endothelialization. Specifically,the Cu^(2+) chelated firmly with a cyclen 1,4,7,10-tetraazacyclododecane-N’, N’’, N’’’, N-tetraacetic acid(DOTA) could form a stability of hybrid coating, avoiding the explosion of Cu^(2+). The chelated Cu^(2+) enabled the catalytic generation of NO and promoted the adhesion and proliferation of endothelial cells(ECs) in vascular micro-environment. In this case, the synergistic effect of NO-generation and endothelial glycocalyx molecules of HA lead to efficient ECs promotion and smooth muscle cells(SMCs) inhibition. Meanwhile, the blood compatibility also had achieved a marked improvement. Moreover, the standard electrochemical measurements indicated that the functionalized ZE21B alloy had better anti-corrosion ability. In a conclusion, the dual-functional coating displays a great potential in the field of biodegradable magnesium-based implantable cardiovascular stents.展开更多
A novel amperometric sensor for the determination of nitric oxide was developed by coating polythionine / nation on a glassy carbon electrode. This sensor exhibited a great enhancement to the oxidation of nitric oxide...A novel amperometric sensor for the determination of nitric oxide was developed by coating polythionine / nation on a glassy carbon electrode. This sensor exhibited a great enhancement to the oxidation of nitric oxide. The oxidation peak currents were linear to the concentration of nitric oxide over the wide range from 3.6×10^-7 to 6.8×10^-5 mol·L^-1, and the detection limit was 7.2×10^-8 mol·L^-1. Experimental results showed that this nitric oxide sensor possessed excellent selectivity and longer stability. NO releasing from rat kidney was monitored by this sensor.展开更多
The cytoprotective messenger nitric oxide (NO) and cytotoxic peroxynitrite (ONOO-) are the main components of oxidative stress and can be generated by endothelial cells. A tandem of electrochemical nanosensors (diamet...The cytoprotective messenger nitric oxide (NO) and cytotoxic peroxynitrite (ONOO-) are the main components of oxidative stress and can be generated by endothelial cells. A tandem of electrochemical nanosensors (diameter 200-300 nm) were used to measure, in situ, the balance between NO and ONOO-produced by human umbilical vein endothelial cells (HUVEC’s). The amperometric nanosensors were placed 5 ± 2 μm from the surface of the endothelial cells and the concentration of NO and ONOO- was measured at 630 mV and -300 mV (vs Ag/AgCl) respectively. Normal, functional, endothelial cells produced maximal 450 ± 25 nmol.L-1 of NO and 180 ± 15 nmol.L-1 of ONOO- in about 3 s, after stimulation with calcium ionophore. The in situ measurements of NO and ONOO- were validated using nitric oxide synthase inhibitor L-NMMA, ONOO- scavenger Mn(III) porphyrin, and superoxide dismutase (PEG-SOD). The ratio of NO concentration to ONOO- concentration ([NO]/[ONOO-]) was introduced for quantification of both, the redox balance and the level of the nitroxidative stress in the endothelium. [NO]/[ONOO-] was 2.7 ± 0.1 in a functional endothelium. The model of the dysfunctional endothelium was made by the treatment of HUVEC’s with angiotensin II for 20 min. Dysfunctional HUVEC’s produced only 115 ± 15 nmol.L-1 of NO, but generated a significantly higher concentration of ONOO- of 490 ± 30 nmol.L-1. The [NO]/[ONOO-] ratio decreased to 0.23 ± 0.14 in the dysfunctional endothelium. Electrochemical nanosensors can be effectively used for in situ monitoring of changing levels of nitroxidative/ oxidative stress, and may be useful in early medical diagnosis of the cardiovascular system.展开更多
基金supported by the National Key R&D Program of China,No.2019YFE0121200(to LQZ)the National Natural Science Foundation of China,Nos.82325017(to LQZ),82030032(to LQZ),82261138555(to DL)+2 种基金the Natural Science Foundation of Hubei Province,No.2022CFA004(to LQZ)the Natural Science Foundation of Jiangxi Province,No.20224BAB206040(to XZ)Research Project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province,No.RZYB202201(to XZ).
文摘With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.
基金supported by National Natural Science Foundation of China(52260012)Natural Science Foundation of Jiangxi Province(20232BAB203053,20212ACB213001,20232BAB203033)+1 种基金General Project of Jiangxi Province Key Research and Development Program(20192BBG70008)Training Plan for Academic and Technical Leaders of Major Disciplines in Jiangxi Province-youth Talent Project(20232BCJ23047).
文摘During wet complexation denitrification of flue gas,Fe^(Ⅱ)EDTA regeneration,also known as reducing Fe^(Ⅱ)EDTA and Fe^(Ⅱ)EDTA-nitric oxide(NO)to Fe^(Ⅱ)EDTA,is crucial.In this paper,ultraviolet(UV)light was used for the first time to reduce Fe^(Ⅱ)EDTA-NO.The experimental result demonstrated that Fe^(Ⅱ)EDTA-NO reduction rate increased with UV power increasing,elevated temperature,and initial Fe^(Ⅱ)EDTA-NO concentration decreasing.Fe^(Ⅱ)EDTA-NO reduction rate increased first and then decreased as pH value increased(2.0-10.0).Fe^(Ⅱ)EDTA-NO reduction with UV irradiation presented a first order reaction with respect to Fe^(Ⅱ)EDTA-NO.Compared with other Fe^(Ⅱ)EDTA regeneration methods,Fe^(Ⅱ)EDTA regeneration with UV show more superiority through comprehensive consideration of regeneration rate and procedure.Subsequently,NO absorption experiment by Fe^(Ⅱ)EDTA solution with UV irradiation confirmed that UV can significantly promote the NO removal performance of Fe^(Ⅱ)EDTA.Appropriate oxygen concentration(3%(vol))and acidic environment(pH=4)was favorable for NO removal.With UV power increasing as well as temperature decreasing,NO removal efficiency rose.In addition,the mechanism research indicates that NO from flue gas is mostly converted to NO_(2)-,NO_(3)-,NH_(4)^(+),N_(2),and N_(2)O with Fe^(Ⅱ)EDTA absorption liquid with UV irradiation.UV strengthens NO removal in Fe^(Ⅱ)EDTA absorption liquid by forming a synergistic effect of oxidation-reduction-complexation.Finally,compared with NO removal methods with Fe^(Ⅱ)EDTA,Fe^(Ⅱ)EDTA combined UV system shows prominent technology advantage in terms of economy and secondary pollution.
基金financially supported by the National Natural Science Foundation of China(82101069,82102537,82160411,82002278)the Natural Science Foundation of Chongqing Science and Technology Commission(CSTC2021JCYJ-MSXMX0170,CSTB2022BSXM-JCX0039)+2 种基金the First Affiliated Hospital of Chongqing Medical University Cultivating Fund(PYJJ2021-02)the Beijing Municipal Science&Technology Commission(Z221100007422130)the Youth Incubation Program of Medical Science and Technology of PLA(21QNPY116).
文摘Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.
基金supported by the Russian Science Foundation(grant No.22-19-00037),https://rscf.ru/project/22-19-00037/.
文摘The hydrothermal synthesis of In_(2)O_(3)and CeO_(2)–In_(2)O_(3)is investigated as well as the properties of sensor layers based on these compounds.During the synthesis of In_(2)O_(3),intermediate products In(OH)_(3)and InOOH are formed,which are the precursors of stable cubic(c-In_(2)O_(3))and metastable rhombohedral(rh-In_(2)O_(3))phases,respectively.A transition from c-In_(2)O_(3)to rh-In_(2)O_(3)is observed with the addition of CeO_(2).The introduction of cerium into rh-In_(2)O_(3)results in a decrease in the sensor response to hydrogen,while it increases in composites based on c-In_(2)O_(3).The data on the sensor activity of the composites correlate with XPS results in which CeO_(2)causes a decrease in the concentrations of chemisorbed oxygen and oxygen vacancies in rh-In_(2)O_(3).The reverse situation is observed in composites based on c-In_(2)O_(3).Compared to In_(2)O_(3)and CeO_(2)–In_(2)O_(3)obtained by other methods,the synthesized composites demonstrate maximum response to H_(2)at low temperatures by 70–100℃,and have short response time(0.2–0.5 s),short recovery time(6–7 s),and long-term stability.A model is proposed for the dependence of sensitivity on the direction of electron transfer between In_(2)O_(3)and CeO_(2).
基金Open Project of Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake,Grant Number HZHLAB2201.
文摘Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in modulating the plant’s response to iron deficiency.Iron deficiency leads to an increase in the activity of heme oxygenase(HO)and the subsequent generation of CO.Additionally,it alters the polar subcellular distribution of Pin-Formed 1(PIN1)proteins,resulting in enhanced auxin transport.This alteration,in turn,leads to an increase in NO accumulation.Furthermore,iron deficiency enhances the activity of ferric chelate reductase(FCR),as well as the expression of the Fer-like iron deficiency-induced transcription factor 1(FIT)and the ferric reduction oxidase 2(FRO2)genes in plant roots.Overexpression of the long hypocotyl 1(HY1)gene,which encodes heme oxygenase,or the CO donor treatment resulted in enhanced basipetal auxin transport,higher FCR activity,and the expression of FIT and FRO2 genes under Fe deficiency.Here,a potential mechanism is proposed:CO and NO interact with auxin to address iron deficiency stress.CO alters auxin transport,enhancing its accumulation in roots and up-regulating key iron-related genes like FRO2 and IRT1.Elevated auxin levels affect NO signaling,leading to greater sensitivity in root development.This interplay promotes FCR activity,which is crucial for iron absorption.Together,these molecules enhance iron uptake and root growth,revealing a novel aspect of plant physiology in adapting to environmental stress.
文摘BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as complications and adverse outcomes persist.Incorporating humanized nursing modes and novel treatments like nitric oxide inhalation may enhance recovery and reduce postoperative complications.AIM To evaluate the effects of a humanized nursing mode combined with nitric oxide inhalation on the rehabilitation outcomes of patients undergoing lung surgery,focusing on pulmonary function,recovery speed,and overall treatment costs.METHODS A total of 79 patients who underwent lung surgery at a tertiary hospital from March 2021 to December 2021 were divided into a control group(n=39)receiving a routine nursing program and an experimental group(n=40)receiving additional humanized nursing interventions and atomized inhalation of nitric oxide.Key indicators were compared between the two groups alongside an analysis of treatment costs.RESULTS The experimental group demonstrated significant improvements in pulmonary function,reduced average recovery time,and lower total treatment costs compared to the control group.Moreover,the quality of life in the experimental group was significantly better in the 3 months post-surgery,indicating a more effective rehabilitation process.CONCLUSION The combination of humanized nursing mode and nitric oxide inhalation in postoperative care for lung surgery patients significantly enhances pulmonary rehabilitation outcomes,accelerates recovery,and reduces economic burden.This approach offers a promising reference for improving patient care and rehabilitation efficiency following lung surgery.
基金supported by the National Research Foundation of Korea(NRF)grants funded by the Ministry of Science and ICT(MSIT)(RS-2023-00251283,and 2022M3D1A2083618)by the Ministry of Education(2020R1A6A1A03040516).
文摘Advancements in sensor technology have significantly enhanced atmospheric monitoring.Notably,metal oxide and carbon(MO_(x)/C)hybrids have gained attention for their exceptional sensitivity and room-temperature sensing performance.However,previous methods of synthesizing MO_(x)/C composites suffer from problems,including inhomogeneity,aggregation,and challenges in micropatterning.Herein,we introduce a refined method that employs a metal–organic framework(MOF)as a precursor combined with direct laser writing.The inherent structure of MOFs ensures a uniform distribution of metal ions and organic linkers,yielding homogeneous MO_(x)/C structures.The laser processing facilitates precise micropatterning(<2μm,comparable to typical photolithography)of the MO_(x)/C crystals.The optimized MOF-derived MO_(x)/C sensor rapidly detected ethanol gas even at room temperature(105 and 18 s for response and recovery,respectively),with a broad range of sensing performance from 170 to 3,400 ppm and a high response value of up to 3,500%.Additionally,this sensor exhibited enhanced stability and thermal resilience compared to previous MOF-based counterparts.This research opens up promising avenues for practical applications in MOF-derived sensing devices.
基金supported by the National Key R&D Program of China(No.2020YFB2008604,2021YFB3202500)the National Natural Science Foundation of China(No.61874034)the International Science and Technology Cooperation Program of Shanghai Science and Technology Innovation Action Plan(No.21520713300)。
文摘Highly sensitive gas sensors with remarkably low detection limits are attractive for diverse practical application fields including real-time environmental monitoring,exhaled breath diagnosis,and food freshness analysis.Among various chemiresistive sensing materials,noble metal-decorated semiconducting metal oxides(SMOs)have currently aroused extensive attention by virtue of the unique electronic and catalytic properties of noble metals.This review highlights the research progress on the designs and applications of different noble metal-decorated SMOs with diverse nanostructures(e.g.,nanoparticles,nanowires,nanorods,nanosheets,nanoflowers,and microspheres)for high-performance gas sensors with higher response,faster response/recovery speed,lower operating temperature,and ultra-low detection limits.The key topics include Pt,Pd,Au,other noble metals(e.g.,Ag,Ru,and Rh.),and bimetals-decorated SMOs containing ZnO,SnO_(2),WO_(3),other SMOs(e.g.,In_(2)O_(3),Fe_(2)O_(3),and CuO),and heterostructured SMOs.In addition to conventional devices,the innovative applications like photo-assisted room temperature gas sensors and mechanically flexible smart wearable devices are also discussed.Moreover,the relevant mechanisms for the sensing performance improvement caused by noble metal decoration,including the electronic sensitization effect and the chemical sensitization effect,have also been summarized in detail.Finally,major challenges and future perspectives towards noble metal-decorated SMOs-based chemiresistive gas sensors are proposed.
基金supported by the National Natural Science Foundation of China,Nos. 82071556 (to WM), 81873793 (to WM), 82001198 (to YQZ), 82101310 (to DQL)the National Key Research and Development Program of China,No. 2020YFC2005300 (to WM)。
文摘Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain, including neuropathic pain, bone cancer pain, inflammatory pain, and morphine tolerance. The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase, which leads to subsequent production of cGMP. cGMP then activates cGMP-dependent protein kinase(PKG), resulting in the activation of multiple targets such as the opening of ATP-sensitive K+ channels. The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules, as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain. In dorsal root ganglion neurons, natriuretic peptide binds to particulate guanylyl cyclase, generating and further activating the cGMP/PKG pathway, and it also contributes to the development of chronic pain. Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models. Notably the NO/cGMP signaling pathway induces expression of downstream effectors, exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain. These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain, and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy.
基金supported by the Natural Science Foundation of ChinaNos.81971212 (to FG)+7 种基金81601129 (to XXX)the Open Fund of the Key Laboratory of Medical ElectrophysiologyMinistry of Education&Medical Electrophysiological Key Laboratory of Sichuan ProvinceInstitute of Cardiovascular ResearchSouthwest Medical UniversityNo.KeyME-2018-07 (to FG)Liaoning Province Xingliao Talent Program ProjectNo.XLYC1907164 (to FG)
文摘Dysfunction of neuronal nitric oxide synthase contributes to neurotoxicity,which triggers cell death in various neuropathological diseases,including epilepsy.Studies have shown that inhibition of neuronal nitric oxide synthase activity increases the epilepsy threshold,that is,has an anticonvulsant effect.However,the exact role and potential mechanism of neuronal nitric oxide synthase in seizures are still unclear.In this study,we performed RNA sequencing,functional enrichment analysis,and weighted gene coexpression network analysis of the hippocampus of tremor rats,a rat model of genetic epilepsy.We found damaged hippocampal mitochondria and abnormal succinate dehydrogenase level and Na+-K+-ATPase activity.In addition,we used a pilocarpine-induced N2a cell model to mimic epileptic injury.After application of neuronal nitric oxide synthase inhibitor 7-nitroindazole,changes in malondialdehyde,lactate dehydrogenase and superoxide dismutase,which are associated with oxidative stress,were reversed,and the increase in reactive oxygen species level was reversed by 7-nitroindazole or reactive oxygen species inhibitor N-acetylcysteine.Application of 7-nitroindazole or N-acetylcysteine downregulated the expression of caspase-3 and cytochrome c and reversed the apoptosis of epileptic cells.Furthermore,7-nitroindazole or N-acetylcysteine downregulated the abnormally high expression of NLRP3,gasdermin-D,interleukin-1βand interleukin-18.This indicated that 7-nitroindazole and N-acetylcysteine each reversed epileptic cell death.Taken together,our findings suggest that the neuronal nitric oxide synthase/reactive oxygen species pathway is involved in pyroptosis of epileptic cells,and inhibiting neuronal nitric oxide synthase activity or its induced oxidative stress may play a neuroprotective role in epilepsy.
基金supported by the Natural Nature Science Foundation of China,Nos.82030071,81874004the Science and Technology Major Project of Changsha,No.kh2103008(all to JZH).
文摘Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of angiogenesis during the regeneration process,we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells,thereby promoting microvascular regeneration in aged mice after spinal cord injury.In this study,we established young and aged mouse models of contusive spinal cord injury using a modified Allen method.We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord.Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro.Furthermore,intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord,thereby improving neurological function.The role of metformin was reversed by compound C,an adenosine monophosphate-activated protein kinase inhibitor,both in vivo and in vitro,suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury.These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway,thereby improving the neurological function of aged mice after spinal cord injury.
基金All experimental procedures pursued the relevant guidelines and regulations of the National Institute of Health Guide for the Care and Use of Laboratory Animals(NIH Publications No.80-23,revised 1978)were approved by the Ethics Committee of Mashhad University of Medical Sciences,Iran(IR.MUMS.fm.REC.1397.139).
文摘Background:Zataria multiflora and carvacrol showed various pharmacological prop-erties including anti-inflammatory and anti-oxidant effects.However,up to now no studies have explored its potential benefits in ameliorating sepsis-induced aortic and cardiac injury.Thus,this study aimed to investigate the effects of Z.multiflora and carvacrol on nitric oxide(NO)and oxidative stress indicators in lipopolysaccharide(LPS)-induced aortic and cardiac injury.Methods:Adult male Wistar rats were assigned to:Control,lipopolysaccharide(LPS)(1 mg/kg,intraperitoneal(i.p.)),and Z.multiflora hydro-ethanolic extract(ZME,50–200 mg/kg,oral)-and carvacrol(25–100 mg/kg,oral)-treated groups.LPS was in-jected daily for 14 days.Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration.At the end of the study,the levels of malondialdehyde(MDA),NO,thiols,and antioxidant enzymes were evaluated.Results:Our findings showed a significant reduction in the levels of superoxide dis-mutase(SOD),catalase(CAT),and thiols in the LPS group,which were restored by ZME and carvacrol.Furthermore,ZME and carvacrol decreased MDA and NO in car-diac and aortic tissues of LPS-injected rats.Conclusions:The results suggest protective effects of ZME and carvacrol on LPS-induced cardiovascular injury via improved redox hemostasis and attenuated NO pro-duction.However,additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.
文摘Chinese tonifying herbs, which are classified into four functional categories (namely, Yang, Qi, Yin, Blood) are commonly used for restoring normal body function and the prevention of diseases. To explore cell-based biological markers for Blood-enriching Chinese herbs, we investigate the effect of 11 commonly used Blood-enriching herbs on erythropoietin (EPO) production in HepG2 cells. Herbs for nourishing Yin were tested for determining the specificity of Blood-enriching herbs in inducing EPO production. In addition, the effects of Blood-enriching herbs on nitric oxide (NO) production in both HepG2 cells and human umbilical vein endothelial cells (HUVECs) were also investigated. The results indicated that methanolic extracts of Blood-enriching herbs (but not Yin-nourishing herbs) showed characteristic pharmacological activity in inducing EPO production in HepG2 cells and NO release in HUVECs. The experimental findings, therefore, support the use of cell-based EPO production and NO release as biological markers for Blood-enriching Chinese tonifying herbs.
文摘BACKGROUND Although the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)induces more rapid liver regeneration than portal vein embolization,the mechanism remains unclear.AIM To assess the influence of inflammatory cytokines and endothelial nitric oxide synthase(eNOS)activation on liver regeneration in ALPPS.METHODS The future liver remnant/body weight(FLR/BW)ratio,hepatocyte proliferation,inflammatory cytokine expression,and activation of the Akt-eNOS pathway were evaluated in rat ALPPS and portal vein ligation(PVL)models.Hepatocyte proliferation was assessed based on Ki-67 expression,which was confirmed using immunohistochemistry.The serum concentrations of inflammatory cytokines were measured using enzyme linked immune-solvent assays.The Akt-eNOS pathway was assessed using western blotting.To explore the role of inflammatory cytokines and NO,Kupffer cell inhibitor gadolinium chloride(GdCl3),NOS inhibitor N-nitro-arginine methyl ester(L-NAME),and NO enhancer molsidomine were administered intraperitoneally.RESULTS The ALPPS group showed significant FLR regeneration(FLR/BW:1.60%±0.08%,P<0.05)compared with that observed in the PVL group(1.33%±0.11%)48 h after surgery.In the ALPPS group,serum interleukin-6 expression was suppressed using GdCl3 to the same extent as that in the PVL group.However,the FLR/BW ratio and Ki-67 labeling index were significantly higher in the ALPPS group administered GdCl3(1.72%±0.19%,P<0.05;22.25%±1.30%,P<0.05)than in the PVL group(1.33%±0.11%and 12.78%±1.55%,respectively).Phospho-Akt Ser473 and phospho-eNOS Ser1177 levels were enhanced in the ALPPS group compared with those in the PVL group.There was no difference between the ALPPS group treated with L-NAME and the PVL group in the FLR/BW ratio and Ki-67 labeling index.In the PVL group treated with molsidomine,the FLR/BW ratio and Ki-67 labeling index increased to the same level as in the ALPPS group.CONCLUSION Early induction of inflammatory cytokines may not be pivotal for accelerated FLR regeneration after ALPPS,whereas Akt-eNOS pathway activation may contribute to accelerated regeneration of the FLR.
基金supported by the National Natural Science Foundation of China(32071808).
文摘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.
文摘BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.
基金supported by the Natural Science Foundation of Shandong Province(No.ZR2020QC214)the Young Experts of Taishan Scholars(No.tsqn201909130)+3 种基金the Science and Technology Support Plan for Youth Innovation of Colleges and Universities in Shandong Province(No.2019KJF003)the‘First Class Fishery Discipline’Programme in Shandong Provincea special talent programme‘One Thing One Decision(YishiYiyi)’Programme in Shandong Province,Chinathe Breeding Plan of Shandong Provincial Qingchuang Research Team(2019)。
文摘Neuronal nitric oxide synthase(nNOS)was the producer of nitric oxide(NO)which played important gas messenger molecules in biological process.It also can take effect as immune regulation molecule in organism.Black rockfish(Sebastes schlegelii)is an important economic fish which were widely farmed in East Asia countries.Meanwhile,the pathogenic bacteria such as the Edwardsiella tarda and Vibrio anguillarum in seawater always brought serious obstacles to their healthy growth.In order to explore the expression pattern of n NOS gene under the pathogen stimulation and predict its immune function,the n NOS gene in black rockfish named Ssn NOS was identified.It was 3780 bp in length,located on chromosome 6,and contained 27 coding domain sequence(CDs).According to the phylogenetic analysis,the Ssn NOS showed closest relative to the counterpart gene of swamp eel(Monopterus albus).Meanwhile,analysis of Ssn NOS expression in various healthy tissues showed that Ssn NOS expression level was highest in healthy brain tissues,followed by intestinal tissues.In addition,Ssn NOS showed significant expression changes in response to stimulation by two pathogens.Particular in gill,the expression of Ssn NOS after pathogenic stimulation increased significantly.The Elisa analysis showed the Ssn NOS content in gills was much higher than that in other tissues at all time points.Moreover,the expression patterns of Ssn NOS in brain,intestine and kidney after stimulation by pathogens showed a distinct expression pattern which first down-regulated and then up-regulated.Therefore,the Ssn NOS may be an important signaling molecule for fish to respond rapidly in immune stimulation.
基金supported by the National Key R&D Program of China (grant number 2021YFC2400700)National Natural Science Foundation of China (Nos.51871004 and U1804251)。
文摘Magnesium-based biodegradable metals as cardiovascular stents have shown a lot of excellent performance, which have been used to treat coronary artery diseases. However, the excessive degradation rate, imperfect biocompatibility and delayed re-endothelialization still lead to a considerable challenge for its application. In this work, to overcome these shortcomings, a compound of catalyzing nitric oxide(NO) generation containing copper ions(Cu^(2+)) and hyaluronic acid(HA), an important component of the extracellular matrix, were covalently immobilized on a hydrofluoric acid(HF)-pretreated ZE21B alloy via amination layer for improving its corrosion resistance and endothelialization. Specifically,the Cu^(2+) chelated firmly with a cyclen 1,4,7,10-tetraazacyclododecane-N’, N’’, N’’’, N-tetraacetic acid(DOTA) could form a stability of hybrid coating, avoiding the explosion of Cu^(2+). The chelated Cu^(2+) enabled the catalytic generation of NO and promoted the adhesion and proliferation of endothelial cells(ECs) in vascular micro-environment. In this case, the synergistic effect of NO-generation and endothelial glycocalyx molecules of HA lead to efficient ECs promotion and smooth muscle cells(SMCs) inhibition. Meanwhile, the blood compatibility also had achieved a marked improvement. Moreover, the standard electrochemical measurements indicated that the functionalized ZE21B alloy had better anti-corrosion ability. In a conclusion, the dual-functional coating displays a great potential in the field of biodegradable magnesium-based implantable cardiovascular stents.
基金This research was supported by the National Natural Science Foundation of China. （Nos. 60571042 and 30370397）
文摘A novel amperometric sensor for the determination of nitric oxide was developed by coating polythionine / nation on a glassy carbon electrode. This sensor exhibited a great enhancement to the oxidation of nitric oxide. The oxidation peak currents were linear to the concentration of nitric oxide over the wide range from 3.6×10^-7 to 6.8×10^-5 mol·L^-1, and the detection limit was 7.2×10^-8 mol·L^-1. Experimental results showed that this nitric oxide sensor possessed excellent selectivity and longer stability. NO releasing from rat kidney was monitored by this sensor.
文摘The cytoprotective messenger nitric oxide (NO) and cytotoxic peroxynitrite (ONOO-) are the main components of oxidative stress and can be generated by endothelial cells. A tandem of electrochemical nanosensors (diameter 200-300 nm) were used to measure, in situ, the balance between NO and ONOO-produced by human umbilical vein endothelial cells (HUVEC’s). The amperometric nanosensors were placed 5 ± 2 μm from the surface of the endothelial cells and the concentration of NO and ONOO- was measured at 630 mV and -300 mV (vs Ag/AgCl) respectively. Normal, functional, endothelial cells produced maximal 450 ± 25 nmol.L-1 of NO and 180 ± 15 nmol.L-1 of ONOO- in about 3 s, after stimulation with calcium ionophore. The in situ measurements of NO and ONOO- were validated using nitric oxide synthase inhibitor L-NMMA, ONOO- scavenger Mn(III) porphyrin, and superoxide dismutase (PEG-SOD). The ratio of NO concentration to ONOO- concentration ([NO]/[ONOO-]) was introduced for quantification of both, the redox balance and the level of the nitroxidative stress in the endothelium. [NO]/[ONOO-] was 2.7 ± 0.1 in a functional endothelium. The model of the dysfunctional endothelium was made by the treatment of HUVEC’s with angiotensin II for 20 min. Dysfunctional HUVEC’s produced only 115 ± 15 nmol.L-1 of NO, but generated a significantly higher concentration of ONOO- of 490 ± 30 nmol.L-1. The [NO]/[ONOO-] ratio decreased to 0.23 ± 0.14 in the dysfunctional endothelium. Electrochemical nanosensors can be effectively used for in situ monitoring of changing levels of nitroxidative/ oxidative stress, and may be useful in early medical diagnosis of the cardiovascular system.
