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
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
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
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
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
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
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
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
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
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
AIM:To examine the relevance of hypoxia inducible factor(HIF-1)and nitric oxide(NO)on the preservation of fatty liver against cold ischemia-reperfusion injury(IRI). METHODS:We used an isolated perfused rat liver model...AIM:To examine the relevance of hypoxia inducible factor(HIF-1)and nitric oxide(NO)on the preservation of fatty liver against cold ischemia-reperfusion injury(IRI). METHODS:We used an isolated perfused rat liver model and we evaluated HIF-1αin steatotic and non-steatotic livers preserved for 24 h at 4℃in University of Wisconsin and IGL-1 solutions,and then subjected to 2 h of normothermic reperfusion.After normoxic reperfusion,liver enzymes,bile production,bromosulfophthalein clearance,as well as HIF-1αand NO[endothelial NO synthase(eNOS)activity and nitrites/nitrates]were also measured.Other factors associated with the higher susceptibility of steatotic livers to IRI,such as mitochondrial damage and vascular resistance were evaluated. RESULTS:A significant increase in HIF-1αwas found in steatotic and non-steatotic livers preserved in IGL-1 after cold storage.Livers preserved in IGL-1 showed a significant attenuation of liver injury and improvement in liver function parameters.These benefits were enhanced by the addition of trimetazidine(an antiischemic drug),which induces NO and eNOS activation, to IGL-1 solution.In normoxic reperfusion,the presence of NO favors HIF-1αaccumulation,promoting also the activation of other cytoprotective genes,such as hemeoxygenase-1. CONCLUSION:We found evidence for the role of the HIF-1α/NO system in fatty liver preservation,especially when IGL-1 solution is used.展开更多
AIM To observe the nitric oxide synthase (NOS) distribution in the esophageal mucosa andhemodynamic changes in cirrhotic rats.METHODS NOS distribution in the loweresophagus of rats with carbon tetrachlorideinduced cir...AIM To observe the nitric oxide synthase (NOS) distribution in the esophageal mucosa andhemodynamic changes in cirrhotic rats.METHODS NOS distribution in the loweresophagus of rats with carbon tetrachlorideinduced cirrhosis was assessed by using NADPHdiaphorase (NADPH-d ) histochemical method.Concentration of NO in serum were measured byfluorometric assay. Mean arterial pressure(MAP), cardiac output (CO), cardiac index (CI),splanchnic vascular resistance (SVR ), andsplanchnic blood flow (SBF ) were alsodetermined using 5’CO-labeled microspheretechnique.RESULTS Intensity of NOS staining in theesophageal epithelium of cirrhotic rats wassignificantly stronger than that in controls.There was a NOS--positive staining area in theendothelia of esophageal submucosal vessels ofcirrhotic rats, but the NOS staining was negativein normal rats. NO concentration of serum incirrhotic rats were significantly higher incomparison with that of controls. Cirrhotic ratshad significantly lower MAP, SVR and higherSBF than those of the controls.CONCLUSION SPlanchnic hyperdynamiccirculatory state was observed in rats withcirrhosis. The endogenous NO may play animportant role in development of esophagealvarices and in changes of hemodynamics incirrhosis.展开更多
The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene...The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300(histone acetyltransferase p300), we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide(NO) concentration. Col ectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.展开更多
Inflammatory bowel disease(IBD)refers to a group of disorders characterized by chronic inflammation of the gastrointestinal(GI)tract.The elevated levels of nitric oxide(NO)in serum and affected tissues;mainly synthesi...Inflammatory bowel disease(IBD)refers to a group of disorders characterized by chronic inflammation of the gastrointestinal(GI)tract.The elevated levels of nitric oxide(NO)in serum and affected tissues;mainly synthesized by the inducible nitric oxide synthase(iNOS)enzyme;can exacerbate GI inflammation and is one of the major biomarkers of GI inflammation.Various natural and synthetic agents are able to ameliorate GI inflammation and decrease iNOS expression to the extent comparable with some IBD drugs.Thereby,the purpose of this study was to gather a list of natural or synthetic mediators capable of modulating IBD through the NO pathway.Electronic databases including Google Scholar and PubMed were searched from 1980 to May 2018.We found that polyphenols and particularly flavonoids are able to markedly attenuate NO production and iNOS expression through the nuclear factorκB(NF-κB)and JAK/STAT signaling pathways.Prebiotics and probiotics can also alter the GI microbiota and reduce NO expression in IBD models through a broad array of mechanisms.A number of synthetic molecules have been found to suppress NO expression either dependent on the NF-κB signaling pathway(i.e.,dexamethasone,pioglitazone,tropisetron)or independent from this pathway(i.e.,nicotine,prednisolone,celecoxib,β-adrenoceptor antagonists).Co-administration of natural and synthetic agents can affect the tissue level of NO and may improve IBD symptoms mainly by modulating the Toll like receptor-4 and NF-κB signaling pathways.展开更多
Peach(Prunus persica Batsch‘Yuhualu’)fruit are sensitive to chilling injury(CI).Proline,polyamine(PA),and nitric oxide(NO)are important small regulators of various metabolic pathways under chilling stress that mitig...Peach(Prunus persica Batsch‘Yuhualu’)fruit are sensitive to chilling injury(CI).Proline,polyamine(PA),and nitric oxide(NO)are important small regulators of various metabolic pathways under chilling stress that mitigate CI.Ethylene is known to promote senescence and CI,while 1-methylcyclopropene(1-MCP)is an antagonist that inhibits the effects of ethylene.However,how1-MCP and ethylene affect proline,PA,and NO levels under chilling stress remains unclear.To address these questions,1-MCP(1μL·L^(−1))and ethylene(1μL·L^(−1))treatments were applied to peach fruit.Fruit were stored at 4°C for 28 d,then moved to 25°C for 3 d immediately after cold storage.Peach fruit exhibited CI symptoms after 7 d of cold storage with enhanced electrolyte leakage and malondialdehyde contents.The 1-MCP treatment significantly(P<0.05)restrained peach CI,and fruit did not exhibit CI symptoms until 14 d of cold storage.Proline and PAs in peach under chilling stress weremostly synthesized from glutamate and arginine,which were catalyzed by1-pyrroline-5-carboxylate synthetase and arginine decarboxylase,respectively.1-MCPtreated fruit exhibited higher proline and PA contents and enhanced chilling tolerance compared to the control,while ethylene-treated fruit had lower proline and PA contents and reduced chilling tolerance.Ethylene-treated fruit,which exhibited more severe CI symptoms compared to the control,had significantly(P<0.05)lower NO contents and NO synthase activities.However,NOmay not be a direct acting factor in 1-MCPinduced chilling tolerance,as 1-MCP-treated fruit had lower NO contents and NO synthase activities compared to the control.In conclusion,proline and PA clearly played direct and important roles in 1-MCP-induced peach chilling tolerance,while NO may not be actively involved.展开更多
BACKGROUND:Previous studies have shown that extracellular signal-regulated kinase 1/2(ERK1/2) and nitric oxide activation play a pivotal role in central sensitization and long-term neuronal plasticity induced by noxio...BACKGROUND:Previous studies have shown that extracellular signal-regulated kinase 1/2(ERK1/2) and nitric oxide activation play a pivotal role in central sensitization and long-term neuronal plasticity induced by noxious stimulation.However,their effects on compressive neuralg formation and maintenance remain poorly understood.OBJECTIVE:To investigate effects of the specific inhibitor of ERK1/2 signal pathway U0126 on neuronal nitric oxide synthase(nNOS) expression in the dorsal horn of the spinal cord in a compressive neuralgia rat model.DESIGN,TIME AND SETTING:A randomized,controlled experiment was performed at the Institu of Otolaryngology,Head and Neck Surgery,First Hospital of Jilin University from July 2008 to Marc 2009.MATERIALS:U0126(Bio-Mol,USA) was used in this study.METHODS:A total of 84 rats were randomly assigned to two groups.In the first part of the experiment,24 rats were used for behavioral testing,and they were randomly assigned to three sub-groups(n = 8):U0126,dimethyl sulfoxide(DMSO) and model control.In the second part of th experiment,60 rats were used for immunofluorescence and Western blot analysis,and they were randomly assigned to six sub-groups(n = 10):sham surgery,model control,U0126 post-injection 0.5,2,12 and 24 hours.Neuropathic pain was produced by chronic compression to the dorsal roo ganglion in rats from each sub-group.Rats in the U0126 group were administered a 5-μg U0126 intrathecal injection,and rats in the DMSO group were administered a 10-μL 5% DMSO intratheca injection.MAIN OUTCOME MEASURES:Changes in mechanical and thermal hyperalgesia were observed using von Frey filaments and thermalqia stimular.Thermal and mechanical hyperalgesia were stimulated at different time points following intrathecal injection of U0126.nNOS activation and expression in the spinal cord dorsal horn were determined by immunofluorescence and Western blot analysis.RESULTS:Intrathecal injection of U0126 significantly attenuated chronic compression of dorsal root ganglion-induced mechanical and thermal hyperalgesia.Immunofluorescence staining results demonstrated that,compared to the sham surgery group,the number of nNOS-positive neurons was significantly increased in the injured spinal dorsal horn in the model control group(P < 0.01).However,compared to the model control group,there were significantly decreasing numbers of nNOS-positive neurons in the U0126 post-injection groups at 0.5-hour,2-hour,and 12-hour(P < 0.05).Western blot analysis revealed similar results.CONCLUSION:Decreased activity in the ERK signal pathway resulted in down regulated nNOS expression in the dorsal horn of the spinal cord.These results suggested that ERK is involved in nitric oxide reaction to neuropathic pain.展开更多
Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despit...Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despite improvements in technology and techniques,complications can occur.The most common complication,arterial spasm,can cause intense pain and,in some cases,procedural failure.The incidence of spasm is dependent on several variables,including operator experience,artery size,and equipment used.An antispasmolytic cocktail can be applied to reduce spasm,which usually includes an exogenous nitric oxide(NO)donor(glyceryl trinitrate).NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention.However,systemic administration can result in unwanted side-effects,such as hypotension.A method that adopts local delivery of NO might be advantageous.This review article describes the mechanisms involved in radial artery spasm,discusses the advantages and disadvantages of current strategies to reduce spasm,and highlight the potential of NO-loaded nanoporous materials for use in this setting.展开更多
The adsorption of nitric oxide adsorption on clean Mod(111), Mo(111)/O2-(4×4), Mo(111)/O2-(1×3), Mo(111)/O2-(112) facets and Mo(111) oxide surfaces was studied. Mass 28 (N2) desorption spectra show two high ...The adsorption of nitric oxide adsorption on clean Mod(111), Mo(111)/O2-(4×4), Mo(111)/O2-(1×3), Mo(111)/O2-(112) facets and Mo(111) oxide surfaces was studied. Mass 28 (N2) desorption spectra show two high temperature peaks at approximate 1030 (β1) and 1200K (β2). For NO exposures less than 0. 1 L only the ft peak was observed. At higher exposures, the ft peak appeared and small amounts of N2O as well as NO desorbed. The preadsorption of oxygen blocked the β2 desorption partially on the (4×4) and (1×3) surfaces and fully on the (112) facet and oxide surfaces. In addition, the β1 desorption peak shifted to higher temperatures with increasing oxygen preexposure.展开更多
Mitochondrial dysfunction and endoplasmic reticulum stress(ERS) are global processes that are interrelated and regulated by several stress factors. Nitric oxide(NO) is a multifunctional biomolecule with many varieties...Mitochondrial dysfunction and endoplasmic reticulum stress(ERS) are global processes that are interrelated and regulated by several stress factors. Nitric oxide(NO) is a multifunctional biomolecule with many varieties of physiological and pathological functions, such as the regulation of cytochrome c inhibition and activation of the immune response, ERS and DNA damage; these actions are dose-dependent. It has been reported that in embryonic stem cells, NO has a dual role, controlling differentiation, survival and pluripotency, but the molecular mechanisms by which it modulates these functions are not yet known. Low levels of NO maintain pluripotency and induce mitochondrial biogenesis. It is well established that NO disrupts the mitochondrial respiratory chain and causes changes in mitochondrial Ca^(2+) flux that induce ERS. Thus, at high concentrations, NO becomes a potential differentiation agent due to the relationship between ERS and the unfolded protein response in many differentiated cell lines. Nevertheless, many studies have demonstratedthe need for physiological levels of NO for a proper ERS response. In this review, we stress the importance of the relationships between NO levels, ERS and mitochondrial dysfunction that control stem cell fate as a new approach to possible cell therapy strategies.展开更多
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.
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 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 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.
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.
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.
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.
基金Supported by The Ministerio de de Sanidad y Consumo(PI081988)CIBER-EHD,Instituto Carlos Ⅲ,Madrid and Ministerio de Asuntos Exteriores y de Cooperación Internacionales(A/020255/08 and A/02987/09),Madrid
文摘AIM:To examine the relevance of hypoxia inducible factor(HIF-1)and nitric oxide(NO)on the preservation of fatty liver against cold ischemia-reperfusion injury(IRI). METHODS:We used an isolated perfused rat liver model and we evaluated HIF-1αin steatotic and non-steatotic livers preserved for 24 h at 4℃in University of Wisconsin and IGL-1 solutions,and then subjected to 2 h of normothermic reperfusion.After normoxic reperfusion,liver enzymes,bile production,bromosulfophthalein clearance,as well as HIF-1αand NO[endothelial NO synthase(eNOS)activity and nitrites/nitrates]were also measured.Other factors associated with the higher susceptibility of steatotic livers to IRI,such as mitochondrial damage and vascular resistance were evaluated. RESULTS:A significant increase in HIF-1αwas found in steatotic and non-steatotic livers preserved in IGL-1 after cold storage.Livers preserved in IGL-1 showed a significant attenuation of liver injury and improvement in liver function parameters.These benefits were enhanced by the addition of trimetazidine(an antiischemic drug),which induces NO and eNOS activation, to IGL-1 solution.In normoxic reperfusion,the presence of NO favors HIF-1αaccumulation,promoting also the activation of other cytoprotective genes,such as hemeoxygenase-1. CONCLUSION:We found evidence for the role of the HIF-1α/NO system in fatty liver preservation,especially when IGL-1 solution is used.
文摘AIM To observe the nitric oxide synthase (NOS) distribution in the esophageal mucosa andhemodynamic changes in cirrhotic rats.METHODS NOS distribution in the loweresophagus of rats with carbon tetrachlorideinduced cirrhosis was assessed by using NADPHdiaphorase (NADPH-d ) histochemical method.Concentration of NO in serum were measured byfluorometric assay. Mean arterial pressure(MAP), cardiac output (CO), cardiac index (CI),splanchnic vascular resistance (SVR ), andsplanchnic blood flow (SBF ) were alsodetermined using 5’CO-labeled microspheretechnique.RESULTS Intensity of NOS staining in theesophageal epithelium of cirrhotic rats wassignificantly stronger than that in controls.There was a NOS--positive staining area in theendothelia of esophageal submucosal vessels ofcirrhotic rats, but the NOS staining was negativein normal rats. NO concentration of serum incirrhotic rats were significantly higher incomparison with that of controls. Cirrhotic ratshad significantly lower MAP, SVR and higherSBF than those of the controls.CONCLUSION SPlanchnic hyperdynamiccirculatory state was observed in rats withcirrhosis. The endogenous NO may play animportant role in development of esophagealvarices and in changes of hemodynamics incirrhosis.
基金supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13010000)the National Natural Science Foundation of China(91631306 to BS,31671329 to XQ,31460287 to Ou,31501013 to HZ,and 31360032 to CC)+2 种基金the National 973 program(2012CB518202 to TW)the State Key Laboratory of Genetic Resources and Evolution(GREKF15-05,GREKF16-04)the Zhufeng Scholar Program of Tibetan University
文摘The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300(histone acetyltransferase p300), we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide(NO) concentration. Col ectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.
文摘Inflammatory bowel disease(IBD)refers to a group of disorders characterized by chronic inflammation of the gastrointestinal(GI)tract.The elevated levels of nitric oxide(NO)in serum and affected tissues;mainly synthesized by the inducible nitric oxide synthase(iNOS)enzyme;can exacerbate GI inflammation and is one of the major biomarkers of GI inflammation.Various natural and synthetic agents are able to ameliorate GI inflammation and decrease iNOS expression to the extent comparable with some IBD drugs.Thereby,the purpose of this study was to gather a list of natural or synthetic mediators capable of modulating IBD through the NO pathway.Electronic databases including Google Scholar and PubMed were searched from 1980 to May 2018.We found that polyphenols and particularly flavonoids are able to markedly attenuate NO production and iNOS expression through the nuclear factorκB(NF-κB)and JAK/STAT signaling pathways.Prebiotics and probiotics can also alter the GI microbiota and reduce NO expression in IBD models through a broad array of mechanisms.A number of synthetic molecules have been found to suppress NO expression either dependent on the NF-κB signaling pathway(i.e.,dexamethasone,pioglitazone,tropisetron)or independent from this pathway(i.e.,nicotine,prednisolone,celecoxib,β-adrenoceptor antagonists).Co-administration of natural and synthetic agents can affect the tissue level of NO and may improve IBD symptoms mainly by modulating the Toll like receptor-4 and NF-κB signaling pathways.
基金This work was supported by the Natural Science Foundation of Jiangsu Province of China(Grant No.BK20140483)China Postdoctoral Science Foundation(Grant No.2014M560451).
文摘Peach(Prunus persica Batsch‘Yuhualu’)fruit are sensitive to chilling injury(CI).Proline,polyamine(PA),and nitric oxide(NO)are important small regulators of various metabolic pathways under chilling stress that mitigate CI.Ethylene is known to promote senescence and CI,while 1-methylcyclopropene(1-MCP)is an antagonist that inhibits the effects of ethylene.However,how1-MCP and ethylene affect proline,PA,and NO levels under chilling stress remains unclear.To address these questions,1-MCP(1μL·L^(−1))and ethylene(1μL·L^(−1))treatments were applied to peach fruit.Fruit were stored at 4°C for 28 d,then moved to 25°C for 3 d immediately after cold storage.Peach fruit exhibited CI symptoms after 7 d of cold storage with enhanced electrolyte leakage and malondialdehyde contents.The 1-MCP treatment significantly(P<0.05)restrained peach CI,and fruit did not exhibit CI symptoms until 14 d of cold storage.Proline and PAs in peach under chilling stress weremostly synthesized from glutamate and arginine,which were catalyzed by1-pyrroline-5-carboxylate synthetase and arginine decarboxylase,respectively.1-MCPtreated fruit exhibited higher proline and PA contents and enhanced chilling tolerance compared to the control,while ethylene-treated fruit had lower proline and PA contents and reduced chilling tolerance.Ethylene-treated fruit,which exhibited more severe CI symptoms compared to the control,had significantly(P<0.05)lower NO contents and NO synthase activities.However,NOmay not be a direct acting factor in 1-MCPinduced chilling tolerance,as 1-MCP-treated fruit had lower NO contents and NO synthase activities compared to the control.In conclusion,proline and PA clearly played direct and important roles in 1-MCP-induced peach chilling tolerance,while NO may not be actively involved.
基金Science and Technology Development Project Program of Jilin Province,China,No. 200505195
文摘BACKGROUND:Previous studies have shown that extracellular signal-regulated kinase 1/2(ERK1/2) and nitric oxide activation play a pivotal role in central sensitization and long-term neuronal plasticity induced by noxious stimulation.However,their effects on compressive neuralg formation and maintenance remain poorly understood.OBJECTIVE:To investigate effects of the specific inhibitor of ERK1/2 signal pathway U0126 on neuronal nitric oxide synthase(nNOS) expression in the dorsal horn of the spinal cord in a compressive neuralgia rat model.DESIGN,TIME AND SETTING:A randomized,controlled experiment was performed at the Institu of Otolaryngology,Head and Neck Surgery,First Hospital of Jilin University from July 2008 to Marc 2009.MATERIALS:U0126(Bio-Mol,USA) was used in this study.METHODS:A total of 84 rats were randomly assigned to two groups.In the first part of the experiment,24 rats were used for behavioral testing,and they were randomly assigned to three sub-groups(n = 8):U0126,dimethyl sulfoxide(DMSO) and model control.In the second part of th experiment,60 rats were used for immunofluorescence and Western blot analysis,and they were randomly assigned to six sub-groups(n = 10):sham surgery,model control,U0126 post-injection 0.5,2,12 and 24 hours.Neuropathic pain was produced by chronic compression to the dorsal roo ganglion in rats from each sub-group.Rats in the U0126 group were administered a 5-μg U0126 intrathecal injection,and rats in the DMSO group were administered a 10-μL 5% DMSO intratheca injection.MAIN OUTCOME MEASURES:Changes in mechanical and thermal hyperalgesia were observed using von Frey filaments and thermalqia stimular.Thermal and mechanical hyperalgesia were stimulated at different time points following intrathecal injection of U0126.nNOS activation and expression in the spinal cord dorsal horn were determined by immunofluorescence and Western blot analysis.RESULTS:Intrathecal injection of U0126 significantly attenuated chronic compression of dorsal root ganglion-induced mechanical and thermal hyperalgesia.Immunofluorescence staining results demonstrated that,compared to the sham surgery group,the number of nNOS-positive neurons was significantly increased in the injured spinal dorsal horn in the model control group(P < 0.01).However,compared to the model control group,there were significantly decreasing numbers of nNOS-positive neurons in the U0126 post-injection groups at 0.5-hour,2-hour,and 12-hour(P < 0.05).Western blot analysis revealed similar results.CONCLUSION:Decreased activity in the ERK signal pathway resulted in down regulated nNOS expression in the dorsal horn of the spinal cord.These results suggested that ERK is involved in nitric oxide reaction to neuropathic pain.
基金Supported by the European Social Fund and Scottish Funding Council as part of Developing Scotland’s Workforce in the Scotland 2014-2020 European Structural and Investment Fund Programme
文摘Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despite improvements in technology and techniques,complications can occur.The most common complication,arterial spasm,can cause intense pain and,in some cases,procedural failure.The incidence of spasm is dependent on several variables,including operator experience,artery size,and equipment used.An antispasmolytic cocktail can be applied to reduce spasm,which usually includes an exogenous nitric oxide(NO)donor(glyceryl trinitrate).NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention.However,systemic administration can result in unwanted side-effects,such as hypotension.A method that adopts local delivery of NO might be advantageous.This review article describes the mechanisms involved in radial artery spasm,discusses the advantages and disadvantages of current strategies to reduce spasm,and highlight the potential of NO-loaded nanoporous materials for use in this setting.
文摘The adsorption of nitric oxide adsorption on clean Mod(111), Mo(111)/O2-(4×4), Mo(111)/O2-(1×3), Mo(111)/O2-(112) facets and Mo(111) oxide surfaces was studied. Mass 28 (N2) desorption spectra show two high temperature peaks at approximate 1030 (β1) and 1200K (β2). For NO exposures less than 0. 1 L only the ft peak was observed. At higher exposures, the ft peak appeared and small amounts of N2O as well as NO desorbed. The preadsorption of oxygen blocked the β2 desorption partially on the (4×4) and (1×3) surfaces and fully on the (112) facet and oxide surfaces. In addition, the β1 desorption peak shifted to higher temperatures with increasing oxygen preexposure.
基金Supported by Ministerio de Ciencia E Innovación-Bernat Soria-Innpacto Proyect,No.IPT-2011-1615-900000Instituto de Salud Carlos III,Gobierno de Espana-Bernat Soria,No.TERCEL RD06/0010/0025+1 种基金Consejeria de Salud Junta de Andalucia-Francisco Javier Bedoya Bergua,No.PI-0105-2010Consejeria de Economia Innovación Ciencia y Empleo-Junta de Andalucia-Francisco Javier Bedoya,No.CTS-7127/2011.
文摘Mitochondrial dysfunction and endoplasmic reticulum stress(ERS) are global processes that are interrelated and regulated by several stress factors. Nitric oxide(NO) is a multifunctional biomolecule with many varieties of physiological and pathological functions, such as the regulation of cytochrome c inhibition and activation of the immune response, ERS and DNA damage; these actions are dose-dependent. It has been reported that in embryonic stem cells, NO has a dual role, controlling differentiation, survival and pluripotency, but the molecular mechanisms by which it modulates these functions are not yet known. Low levels of NO maintain pluripotency and induce mitochondrial biogenesis. It is well established that NO disrupts the mitochondrial respiratory chain and causes changes in mitochondrial Ca^(2+) flux that induce ERS. Thus, at high concentrations, NO becomes a potential differentiation agent due to the relationship between ERS and the unfolded protein response in many differentiated cell lines. Nevertheless, many studies have demonstratedthe need for physiological levels of NO for a proper ERS response. In this review, we stress the importance of the relationships between NO levels, ERS and mitochondrial dysfunction that control stem cell fate as a new approach to possible cell therapy strategies.
