Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expre...Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.展开更多
Lung cancer is the most frequent cause of cancer-related mortality worldwide.Nitric oxide(NO),prostaglandins(PGs),thromboxanes(TXs),and endothelins(ETs)participate in numerous physiological processes.These agents play...Lung cancer is the most frequent cause of cancer-related mortality worldwide.Nitric oxide(NO),prostaglandins(PGs),thromboxanes(TXs),and endothelins(ETs)participate in numerous physiological processes.These agents play an important role in lung carcinogenesis by regulating cancer cell proliferation,apoptosis,invasion,and angiogenesis.NO is a gaseous free radical with tumo-ricidal and tumorigenic activities in lung cancer.Arachidonic acid-derived PGs,including PGD2,PGE2,8-iso-PGF2α,and PGI2,are related to the development of lung cancer.PGD2 and PGI2 act as tumor suppressors,while PGE2 and 8-iso-PGF2αpromote tumor progression.TXA2 catalyzed by cyclooxygenase induces prolif-eration as well as angiogenesis.Elevated levels of TXB2,an inactive metabolite of TXA2,are positively correlated with lung carcinoma stages.ET-1 and ET-2 are 21 amino acid polypeptides;their silencing hinders lung cancer cell proliferation and invasion.ET-2 depletion also triggers apoptotic death.This chapter review aims to provide a comprehensive overview of the role of NO,PGs,TXs,and ETs in lung cancer.展开更多
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
Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral ...Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral blood pressure.While NO is catalyzed by various nitric oxide synthase(NOS)isoforms,the regulatory roles of these types in the hemodynamics of pulmonary and systemic circulation in living hypoxic animals remain unclear.Therefore,this study aims to investigate the regu-latory effects of different NOS isoforms on pulmonary and systemic circulation in hypoxic rats by employing selective NOS inhibitors and continuously monitoring hemodynamic parameters of both pulmonary and systemic circulation.Methods:Forty healthy male Sprague–Dawley(SD)rats were randomly divided into four groups:Control group(NG-nitro-D-arginine methyl ester,D-NAME),L-NAME group(non-selective NOS inhibitor,NG-nitro-L-arginine methyl ester),AG group(in-ducible NOS inhibitor group,aminoguanidine),and 7-NI group(neurological NOS in-hibitor,7-nitroindazole).Hemodynamic parameters of rats were monitored for 10 min after inhibitor administration and 5 min after induction of hypoxia[15%O2,2200 m a.sl.,582 mmHg(76.5 kPa),Xining,China]using the real-time dynamic monitoring model for pulmonary and systemic circulation hemodynamics in vivo.Serum NO concentra-tions and blood gas analysis were measured.Results:Under normoxia,mean arterial pressure and total peripheral vascular resist-ance were increased,and ascending aortic blood flow and serum NO concentration were decreased in the L-NAME and AG groups.During hypoxia,pulmonary arterial pressure and pulmonary vascular resistance were significantly increased in the L-NAME and AG groups.Conclusions:This compensatory mechanism activated by inducible NOS and en-dothelial NOS effectively counteracts the pulmonary hemodynamic changes induced by hypoxic stress.It plays a crucial role in alleviating hypoxia-induced pulmonary arte-rial hypertension.展开更多
Nitric oxide(NO),which generally originates from vehicle exhaust and industrial flue gases,is one of the most serious air pollutants.In this case,the electrochemical NO reduction reaction(NORR)not only removes the atm...Nitric oxide(NO),which generally originates from vehicle exhaust and industrial flue gases,is one of the most serious air pollutants.In this case,the electrochemical NO reduction reaction(NORR)not only removes the atmospheric pollutant NO but also produces valuable ammonia(NH_(3)).Hence,through the synthesis and modification of Fe_(3)C nanocrystal cata-lysts,the as-obtained optimal sample of Fe_(3)C/C-900 was adopted as the NORR catalyst at ambient conditions.As a result,the Fe_(3)C/C-900 catalyst showed an NH_(3)Faraday efficiency of 76.5%and an NH_(3)yield rate of 177.5μmol·h^(-1)·cm^(-2)at the working potentials of-0.8 and-1.2 V versus reversible hydrogen electrode(vs.RHE),respectively.And it delivered a stable NORR activity during the electrolysis.Moreover,we attribute the high NORR properties of Fe_(3)C/C-900 to two aspects:one is the enhanced intrinsic activity of Fe_(3)C nanocrystals,including the lowering of the energy barrier of rate-limiting step(*NOH→*N)and the inhibition of hydrogen evolution;on the other hand,the favorable dispersion of active components,the effective adsorption of gaseous NO,and the release of liquid NH_(3)products facilitated by the porous carbon substrate.展开更多
BACKGROUND Esophageal cancer(ESCA)is among the most prevalent and lethal tumors globally.While nitric oxide synthase 1(NOS1)is recognized for its important in-volvement in various cancers,its specific function in ESCA...BACKGROUND Esophageal cancer(ESCA)is among the most prevalent and lethal tumors globally.While nitric oxide synthase 1(NOS1)is recognized for its important in-volvement in various cancers,its specific function in ESCA remains unclear.AIM To explore the potential role and underlying mechanisms of NOS1 in ESCA.METHODS Survival rates were analyzed using GeneCards and Gene Expression Profiling Interactive Analysis.The effects and mechanisms of NOS1 on ESCA cells were evaluated via the Cell Counting Kit-8 assay,scratch assay,Transwell assay,flow cytometry,quantitative polymerase chain reaction,western blotting,and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining.The protein interaction network was used to screen the interacting proteins of NOS1 and validate these interactions through co-immuno-precipitation and dual luciferase assays.Additionally,a nude mouse xenograft model was established to evaluate the effect of NOS1 in vivo.RESULTS The survival rate of patients with ESCA with high NOS1 expression was higher than that of patients with low NOS1 expression.NOS1 expression in ESCA cell lines was lower than that in normal esophageal epithelial cells.Overexpression of NOS1(oe-NOS1)inhibited proliferation,invasion,and migration abilities in ESCA cell lines,resulting in decreased autophagy levels and increased apoptosis,pyroptosis,and ferroptosis.Protein interaction studies confirmed the interaction between NOS1 and NOS1 adaptor protein(NOS1AP).Following oe-NOS1 and the silencing of NOS1AP,levels of P62 and microtubule-associated protein 1 light chain 3 beta increased both in vitro and in vivo.Furthermore,the expression levels of E-cadherin,along with the activation of phosphatidylinositol 3-kinase(PI3K)and protein kinase B(AKT),were inhibited in ESCA cell lines.CONCLUSION NOS1 and NOS1 proteins interact to suppress autophagy,activate the PI3K/AKT pathway,and exert anti-cancer effects in ESCA.展开更多
Background Persistent pulmonary hypertension(PPHN)of the newborn is one of the major contributors to neonatal mortality.Current conventional treatments for PPHN primarily encompass mechanical ventilation,inhaled nitri...Background Persistent pulmonary hypertension(PPHN)of the newborn is one of the major contributors to neonatal mortality.Current conventional treatments for PPHN primarily encompass mechanical ventilation,inhaled nitric oxide(iNO),sildenafil,and magnesium sulfate.In confirmed cases of neonatal respiratory distress syndrome,pulmonary surfactant(PS)can be considered as a potential treatment option;However,the optimal dosage and administration frequency of PS remain subjects of ongoing debate.This study aimed to assess the efficacy of early repeated endotracheal PS administration combined with iNO therapy in the management of newborns with PPHN.Methods Twenty-three neonates with PPHN received iNO alongside foundational treatments,including anti-infection therapy,mechanical ventilation,acidosis correction,and blood pressure stabilization.The observation group(n=13)received endotracheal instillation of PS three times,with each administration spaced six hours apart;The control group(n=10)received endotracheal instillation of PS once.Parameters compared included blood gas indices,oxygenation index(OI),alveolar-arterial oxygen partial pressure difference(PA-aDO,),pulmonary artery systolic pressure(PAP),and N-terminal pro-brain natriuretic peptide(NT-pro-BNP).Mechanical ventilation duration,oxygen therapy time,hospitalization length,and survival outcomes were recorded and compared between groups.Results The blood gas parameters,OI,and PA-aDO,showed no significant differences between the two groups of children before treatment(P>0.05).By 24-hour post-treatment,both groups exhibited significant increases in partial pressure of oxygen(PaO,)and potential of hydrogen(PH)levels,alongside significant decreases in lactate,partial pressure of carbon dioxide(PaCO,),OI,and PA-aDO2,with statistically significant differences(P<0.05).By 48-hour post-treatment,the observation group demonstrated significantly better improvements in blood gas parameters,OI,and PA-aDO,compared to the control group,and these differences were statistically significant(P<0.05).There was no statistically significant difference in PAP and NT-pro-BNP levels between the two groups before treatment(P>0.05).After treatment,both groups showed significant decreases in PAP and NT-pro-BNP levels(P<0.05),with a more pronounced reduction observed in the observation group(P<0.05).The observation group had significantly shorter durations of mechanical ventilation and oxygen therapy compared to the control group,with statistically significant differences(P<0.05).Additionally,the observation group exhibited a shorter total hospital stay and a lower mortality rate than the control group,though these differences were not statistically significant(P>0.05).Conclusions Early consecutive multiple doses of PS combined with iNO,compared to a single dose,better improves respiratory function indices,maintains stability,reduces pulmonary artery pressure,enhances cardiac function,shortens ventilator dependency,and increases cure rates in PPHN neonates.This approach is particularly suitable for severe PPHN cases,especially those with underlying pulmonary conditions.展开更多
Nitric oxide(NO)modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies.Althoug...Nitric oxide(NO)modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies.Although a nanoengineering strategy has been proposed to overcome deficiencies of NO gas or small NO donor molecules,such as short half-life,lipophilicity,non-selectivity,and poor stability,it remains challenging to prepare NO nanomedicines with simple composition,multiple functions and enhanced therapeutic efficacy.Herein,we build a liquid metal nanodroplet(LMND)-based NO nanogenerator(LMND@HSG)that is stabilized by a bioreducible guanylated hyperbranched poly(amido amine)(HSG)ligand.Mechanically,the tumor microenvironment specifically triggers a cascade process of glutathione elimination,reactive oxygen species(ROS)generation,and NO release.According to actual demand,the ROS and NO concentrations could be readily controlled by tuning the LMND and HSG feed amounts.Along with the intrinsic anticancer property of LMND(ROS-mediated apoptosis and anti-angiogenesis),LMND@HSG administration could further enhance tumor growth suppression compared with LMND and HSG alone.Fromthis study,leveraging LMND for NO gas therapy provides more possibilities for the prospect of LMND-based anticancer nanomedicines.展开更多
The influence of grain size or grain refinement on the corrosion of Zr alloy is clarified by employing a series of electrochemical analyses and characterization techniques.The corrosion resistance,as a function of exp...The influence of grain size or grain refinement on the corrosion of Zr alloy is clarified by employing a series of electrochemical analyses and characterization techniques.The corrosion resistance,as a function of exposure time,F−concentration,and solution temperatures,of Zr alloys with different grain sizes is ascertained.The results confirm that refining the grain size can effectively enhance the short-time corrosion properties of Zr alloy in HNO_(3) with F−.The fine grained Zr alloy(~10μm in diameter)consistently exhibits a lower corrosion current density,ranging from 18%to 46%lower than that of the coarse-grained Zr alloy(~44μm).The enhanced corrosion resistance is attributed to the high density grain boundaries,which promote oxide stability,and accelerate the creation of the protective layer.The high corrosion rate and pseudo-passivation behavior of Zr alloys in fluorinated nitric acid originate from the accelerated“dissolution-passivation”of the oxide film.However,the grain refinement does not provide enduring anti-corrosion for Zr alloys.To meet the operation of spent fuel reprocessing,additional systematic efforts are required to evaluate the long term effect of grain refinement.展开更多
The stabilization of active molecules is significantly important for chemistry,especially for the bioactive molecules.In this work,we report the synthesis and characterization of three tetrahedral Fe_(4)L_(6) cages,wh...The stabilization of active molecules is significantly important for chemistry,especially for the bioactive molecules.In this work,we report the synthesis and characterization of three tetrahedral Fe_(4)L_(6) cages,which are water-soluble and functionalized with or without PEG chains.All cages can physically trap NO molecules in their cavities to prevent a reaction with O_(2).Single-crystal X-ray diffraction(SCXRD),Griess assay,electron paramagnetic resonance(EPR)spectroscopy,and fluorescence assay demonstrate that NO molecules were encapsulated and stabilized by these cage molecules through the formation of host-vip supramolecules.These NO-loaded cages show high antibacterial activities for inhibiting Staphylococcus aureus and Escherichia coli,providing a convenient method for making antibiotic agents.Moreover,these PEG-functionalized cages exhibit excellent biocompatibility,providing a new strategy for developing materials for NO delivery in biomedical applications.展开更多
Carbonized melamine foam has been recognized as a promising material for microwave absorption due to its exceptional thermal stability,lightweight,and remarkable dielectric properties.In this study,we investigated the...Carbonized melamine foam has been recognized as a promising material for microwave absorption due to its exceptional thermal stability,lightweight,and remarkable dielectric properties.In this study,we investigated the impact of nitric acid oxidation on the surface of carbonized melamine foam and its microwave absorption properties.The treated foam exhibits optimal reflection loss of−21.51 dB at 13.20 GHz,with an effective absorption bandwidth of 7.04 GHz.The enhanced absorption properties are primarily attributed to the strengthened dielectric loss,improved impedance matching,and increased polarization losses resulting from the oxidized surfaces.This research demonstrates a promising new approach for research into surface treatments to improve the performances of microwave absorbers.展开更多
Electrochemical nitrate reduction(eNO_(3)RR)and nitric oxide reduction(eNORR)to ammonia have emerged as promising and sustainable alternatives to the traditional Haber-Bosch method for ammonia production,particularly ...Electrochemical nitrate reduction(eNO_(3)RR)and nitric oxide reduction(eNORR)to ammonia have emerged as promising and sustainable alternatives to the traditional Haber-Bosch method for ammonia production,particularly within the recently proposed reverse artificial nitrogen cycle route:N_(2)→NO_(x)→NH_(3).Notably,experimental studies have demonstrated that eNORR exhibits superior performance over eNO_(3)RR on Cu6Sn5 catalysts.However,the fundamental mechanisms underlying this difference remain poorly understood.Herein,we performed systematic theoretical calculations to explore the reaction pathways,electronic structure effects,and potential-dependent Faradic efficiency associated with ammonia production via these two distinct electrochemical pathways(eNORR and eNO_(3)RR)on Cu6Sn5.By implementing an advanced‘adaptive electric field controlled constant potential(EFC-CP)’methodology combined with microkinetic modeling,we successfully reproduced the experimental observations and identified the key factors affecting ammonia production in both reaction pathways.It was found that eNORR outperforms eNO_(3)RR because it circumvents the ^(*)NO_(2) dissociation and ^(*)NO_(2) desorption steps,leading to distinct surface coverage of key intermediates between the two pathways.Furthermore,the reaction rates were found to exhibit a pronounced dependence on the surface coverage of ^(*)NO in eNORR and ^(*)NO_(2) in eNO_(3)RR.Specifically,the facile desorption of ^(*)NO_(2) on the Cu6Sn5 surface in eNO_(3)RR limits the attainable surface coverage of ^(*)NO,thereby impeding its performance.In contrast,the eNORR can maintain a high surface coverage of adsorbed ^(*)NO species,contributing to its enhanced ammonia production performance.These fundamental insights provide valuable guidance for the rational design of catalysts and the optimization of reaction routes,facilitating the development of more efficient,sustainable,and scalable techniques for ammonia production.展开更多
OBJECTIVE:To explore the therapeutic effect and target of atractylenolide I(AT-I)on post-infectious irritable bowel syndrome(PI-IBS)rats.METHODS:Therefore,the preliminarily mechanism of AT-I in anti-PI-IBS were first ...OBJECTIVE:To explore the therapeutic effect and target of atractylenolide I(AT-I)on post-infectious irritable bowel syndrome(PI-IBS)rats.METHODS:Therefore,the preliminarily mechanism of AT-I in anti-PI-IBS were first predicted by network pharmacology and molecular docking,then the possible signaling pathways were systematically analyzed.Finally,the potential therapeutic targets and possible signaling pathways of AT-I on PI-IBS in Sprague-Dawley(SD)rat model were verified by experiments.RESULTS:AT-I could alleviate PI-IBS symptoms and reduce the expression of tumor necrosis factorα,interleukin-6 and Interferon-gamma in PI-IBS SD rat model and inhibit the c-Jun N-terminal kinase/inducible nitric oxide synthase(JNK/iNOS)pathway.Notably,AT-I treatment could inhibit the overexpression of polymeraseⅠand transcript release factor(PTRF).CONCLUSION:AT-I could alleviate PI-IBS symptoms through downregulation of PTRF and inhibiting the JNK/iNOS pathway.This study not only provides a scientific basis to clarify the anti-PI-IBS effect of AT-I and its mechanism but also suggests a novel promising therapeutic strategy to treat the PI-IBS.展开更多
When the first fully expanded leaf of wheat ( Triticum aestivum L.) seedlings with two leaves were treated with different concentrations (0.05, 0.10, 0.20 and 0.50 mmol/L) of nitric oxide donor, sodium nitroprusside (...When the first fully expanded leaf of wheat ( Triticum aestivum L.) seedlings with two leaves were treated with different concentrations (0.05, 0.10, 0.20 and 0.50 mmol/L) of nitric oxide donor, sodium nitroprusside (SNP), the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) were reduced by the lower concentrations (0.05, 0.10 and 0.20 mmol/L), but enhanced by the higher concentration of SNP (0.50 mmol/L). The protective effect of 0.10 mmol/L SNP was the most obvious. Furthermore, the treatment with 0.10 mmol/L SNP on the above seedlings until the fourth leaves were fully expanded attenuated the accumulation of H2O2, superoxide anion radical (O-2(-)) and MDA, also counteracted the degradation of chlorophyll and soluble proteins, especally Rubisco, both leading to the effective delay of aging process in wheat leaves. The effects of different SNP concentrations (0.05, 0.10, 0.20, 0.50, 1.00 and 5.00 mmol/L) also displayed a dual role in an aging experiment of chloroplasts in vitro, one of which, 0.2 mmol/L SNP treatment, protected the membrane structure and attenuated the degradation of Rubisco effectively. Based on the present results, it was inferred that lower concentrations of nitric oxide (NO) might play a role in delaying aging process in wheat leaves, i.e., might attribute to decrease the level of reactive oxygen species (ROS) and the alleviation of further oxidative damage caused by ROS.展开更多
In order to remove nitric oxides (NO) from flue gas, experimental studies on the photocatalytic oxidation (PCO) of NO are carried out in an efficient laboratory-scale reactor. Nano-sized TiO2 particles loading on ...In order to remove nitric oxides (NO) from flue gas, experimental studies on the photocatalytic oxidation (PCO) of NO are carried out in an efficient laboratory-scale reactor. Nano-sized TiO2 particles loading on quartz sand are prepared and used as the photocatalyst. Effects of several key operating parameters on NO conversion are investigated, including operating temperature, NO inlet concentration, oxygen percentage, relative humidity and residence time. The results illustrate that the NO inlet concentration, the oxygen percentage and the relative humidity play an important role in the oxidation of NO. A lower NO inlet concentration and a higher oxygen percentage result in a higher NO conversion efficiency. When the relative humidity is 8%, the maximum value of NO conversion efficiency is achieved. In addition, the operating temperature and the residence time have a little effect on the conversion efficiency of NO.展开更多
Effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on the germination and metabolism of reactive oxygen species were surveyed in wheat (Triticum aestivum L.) seeds. Germination of wheat seeds and even t...Effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on the germination and metabolism of reactive oxygen species were surveyed in wheat (Triticum aestivum L.) seeds. Germination of wheat seeds and even the elongation of radicle and plumule were dramatically promoted by SNP treatments during the germination under osmotic stress. Meanwhile, activities of amylase and EP were enhanced, thus leading to the degradation of storage reserve in seeds. After osmotic stress was removed, higher viability of wheat seeds was also maintained. In addition, the activities of CAT, APX and the content of proline were increased by SNP treatment simultaneously, but activities of LOX were inhibited, and both of which were beneficial for improving the antioxidant capacity during the germination of wheat seeds under osmotic stress. It was also shown that the increase of the activity of amylase induced by SNP in embryoless half-seeds of wheat in the beginning period of germination (6 h) might be indirectly related to GA(3).展开更多
Neuronal nitric oxide synthase (nNOS) is mainly expressed in neurons,to some extent in astrocytes and neuronal stem cells.The alternative splicing of nNOS mRNA generates 5 isoforms of nNOS,including nNOS-,nNOS-,nNOS...Neuronal nitric oxide synthase (nNOS) is mainly expressed in neurons,to some extent in astrocytes and neuronal stem cells.The alternative splicing of nNOS mRNA generates 5 isoforms of nNOS,including nNOS-,nNOS-,nNOS-,nNOS-and nNOS-2.Monomer of nNOS is inactive,and dimer is the active form.Dimerization requires tetrahydrobiopterin (BH 4),heme and L-arginine binding.Regulation of nNOS expression relies largely on cAMP response element-binding protein (CREB) activity,and nNOS activity is regulated by heat shock protein 90 (HSP90)/HSP70,calmodulin (CaM),phosphorylation and dephosphorylation at Ser847 and Ser1412,and the protein inhibitor of nNOS (PIN).There are primarily 9 nNOS-interacting proteins,including post-synaptic density protein 95 (PSD95),clathrin assembly lymphoid leukemia (CALM),calcium/calmodulindependent protein kinase II alpha (CAMKIIA),Disks large homolog 4 (DLG4),DLG2,6-phosphofructokinase,muscle type (PFK-M),carboxy-terminal PDZ ligand of nNOS (CAPON) protein,syntrophin and dynein light chain (LC).Among them,PSD95,CAPON and PFK-M are important nNOS adapter proteins in neurons.The interaction of PSD95 with nNOS controls synapse formation and is implicated in N-methyl-D-aspartic acid-induced neuronal death.nNOS-derived NO is implicated in synapse loss-mediated early cognitive/motor deficits in several neuropathological states,and negatively regulates neurogenesis under physiological and pathological conditions.展开更多
[Objective] Effects of different concentrations of nitric oxide on membrane lipid peroxidation of wheat induced by enhanced UV-B radiation were researched,sodium nitroprusside (SNP) was selected as an exogenous nitr...[Objective] Effects of different concentrations of nitric oxide on membrane lipid peroxidation of wheat induced by enhanced UV-B radiation were researched,sodium nitroprusside (SNP) was selected as an exogenous nitric oxide(NO)donor.[Method] There are 3 groups including CK,UV treatment group (B),B+SNP treatment group,0,1,2,3,4 d sampling after treatment respectively,and physiological and biochemical indexes of MDA content and CAT,POD,SOD and so on were determined,repeated 3 times,and statistical analyzed.[Result] The results showed that,after the enhanced UV-B radiation,activity of the catalase (CAT),superoxide dismutase (SOD) and of the guaiacol peroxidase (POD) all reduced apparently,and the concentration of malondialdehyde (MDA) increased obviously,leading to oxidative damage in wheat seedlings.Impose different concentrations of SNP after UV-B radiation,may mitigate oxidative damage of wheat seedling from different degrees,which was in agreement with the effect of making the concentration of MDA decrease and the activity of the CAT,SOD and POD all increased.The mitigation role of 0.01 mol/L SNP was more obvious for roots' oxidative damage,while 0.1 mmol/L SNP is more effective for oxidative damage of leaves.[Conclusion] Exogenous NO donor SNP had obvious relieve effects on oxidative damage of wheat seedlings caused by UV-B radiation,which can enhance adaptive capacity of plants to adversity stress.展开更多
Objective: To investigate the role of PKC isoforms in the regulation of LPS-triggered tumoricidal activity in macrophages and further elucidate its signal mechanisms. Methods: Two macrophage cell lines (P388D1 and RAW...Objective: To investigate the role of PKC isoforms in the regulation of LPS-triggered tumoricidal activity in macrophages and further elucidate its signal mechanisms. Methods: Two macrophage cell lines (P388D1 and RAW264.7) were stimulated by LPS alone, or with long-term of PMA pretreatment. Then cytotoxicities to P815 cells (by MTT assay) and IL-1, TNF- (by ELISA) and nitric oxide (NO) production (by Griess reagent) in supernatants were measured. Western blot for PKC isoforms after long-term PMA pretreatment was analyzed. Results: RAW264.7 cells were stimulated with LPS to kill target tumor cells P815, whereas P388D1 cells failed to develop such an ability. Down-regulation of PKC isoforms by chronic treatment with PMA significantly inhibited the LPS-induced cytotoxicity in RAW264.7 cells. In unstimulated state, Western blotting with rabbit antiserum specific for the PKC, 1, 2, or showed all 5 isoforms were detected in P388D1 cells, while only PKC, PKC1 and PKC were detected in RAW264.7 cells. Exposure of the cells to long-term of PMA treatment significantly down-regulated the expression of PKC, PKC1 and PKC in RAW264.7 cells. But in P388D1 cells, although PKC, PKC and PKC were down-regulated, the expression of PKC1 and PKC2 could not be regulated. Comparing with LPS-induced IL-1, TNF- and NO production by the two macrophage cell lines, P388D1 failed to produce NO. In RAW264.7 cells, LPS-induced NO production and antitumor activity was attenuated by the addition of L-NAME, an iNOS inhibitor. Conclusion: The results indicated a critical role of PKC in LPS-induced antitumor activity and this cytotoxicity is mainly due to PKC- mediated NO production by RAW264.7 cells, but not a direct cytotoxic activity.展开更多
Objective To investigate the effect of nitric oxide (NO) on the expression of apelin receptor mRNA, as well as their correlation, in the caudate nucleus of rat. Methods L-Arginine (L-Arg), N^G-nitro-L-arginine met...Objective To investigate the effect of nitric oxide (NO) on the expression of apelin receptor mRNA, as well as their correlation, in the caudate nucleus of rat. Methods L-Arginine (L-Arg), N^G-nitro-L-arginine methyl ester (L-NAME) and normal saline (NS) was separately microinjected into rat caudate nucleus. Expressions of neuronal NO synthase (nNOS) mRNA and apelin receptor mRNA were detected by RT-PCR at 4, 8, 12, 24 and 48 h after microinjection, and their correlation was determined. Results The expressions of nNOS mRNA and apelin receptor mRNA were both significantly increased after microinjection of L-Arg, but significantly decreased after microinjection of L-NAME compared with the NS control group. The nNOS mRNA had a positive correlation with the expression of apelin receptor mRNA after microinjection of L-Arg and L-NAME. Conclusion The activity of NOS in the central nervous system, especially in the caudate nucleus, is one of the key factors for NO to exert many kinds of biological actions, such as modulation of central pain, as a neurotransmitter. The neurobiological action of NO in rat caudate nucleus may be associated with apelin receptors.展开更多
文摘Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.
文摘Lung cancer is the most frequent cause of cancer-related mortality worldwide.Nitric oxide(NO),prostaglandins(PGs),thromboxanes(TXs),and endothelins(ETs)participate in numerous physiological processes.These agents play an important role in lung carcinogenesis by regulating cancer cell proliferation,apoptosis,invasion,and angiogenesis.NO is a gaseous free radical with tumo-ricidal and tumorigenic activities in lung cancer.Arachidonic acid-derived PGs,including PGD2,PGE2,8-iso-PGF2α,and PGI2,are related to the development of lung cancer.PGD2 and PGI2 act as tumor suppressors,while PGE2 and 8-iso-PGF2αpromote tumor progression.TXA2 catalyzed by cyclooxygenase induces prolif-eration as well as angiogenesis.Elevated levels of TXB2,an inactive metabolite of TXA2,are positively correlated with lung carcinoma stages.ET-1 and ET-2 are 21 amino acid polypeptides;their silencing hinders lung cancer cell proliferation and invasion.ET-2 depletion also triggers apoptotic death.This chapter review aims to provide a comprehensive overview of the role of NO,PGs,TXs,and ETs in lung cancer.
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This work was supported by the National Natural Science Foundation of China(grant numbers 81560301 and 81160012)the Natural Science Foundation of Qinghai Province(grant number 2022-ZJ-905)‘2022 Qinghai Province Kunlun Talents High-end Innovation and Entrepreneurship Talents’Outstanding Talent Project.
文摘Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral blood pressure.While NO is catalyzed by various nitric oxide synthase(NOS)isoforms,the regulatory roles of these types in the hemodynamics of pulmonary and systemic circulation in living hypoxic animals remain unclear.Therefore,this study aims to investigate the regu-latory effects of different NOS isoforms on pulmonary and systemic circulation in hypoxic rats by employing selective NOS inhibitors and continuously monitoring hemodynamic parameters of both pulmonary and systemic circulation.Methods:Forty healthy male Sprague–Dawley(SD)rats were randomly divided into four groups:Control group(NG-nitro-D-arginine methyl ester,D-NAME),L-NAME group(non-selective NOS inhibitor,NG-nitro-L-arginine methyl ester),AG group(in-ducible NOS inhibitor group,aminoguanidine),and 7-NI group(neurological NOS in-hibitor,7-nitroindazole).Hemodynamic parameters of rats were monitored for 10 min after inhibitor administration and 5 min after induction of hypoxia[15%O2,2200 m a.sl.,582 mmHg(76.5 kPa),Xining,China]using the real-time dynamic monitoring model for pulmonary and systemic circulation hemodynamics in vivo.Serum NO concentra-tions and blood gas analysis were measured.Results:Under normoxia,mean arterial pressure and total peripheral vascular resist-ance were increased,and ascending aortic blood flow and serum NO concentration were decreased in the L-NAME and AG groups.During hypoxia,pulmonary arterial pressure and pulmonary vascular resistance were significantly increased in the L-NAME and AG groups.Conclusions:This compensatory mechanism activated by inducible NOS and en-dothelial NOS effectively counteracts the pulmonary hemodynamic changes induced by hypoxic stress.It plays a crucial role in alleviating hypoxia-induced pulmonary arte-rial hypertension.
基金supported by the Guangxi Natural Science Fund for Distinguished Young Scholars(2024GXNSFFA010008)Shenzhen Science and Technology Program(JCYJ20230807112503008).
文摘Nitric oxide(NO),which generally originates from vehicle exhaust and industrial flue gases,is one of the most serious air pollutants.In this case,the electrochemical NO reduction reaction(NORR)not only removes the atmospheric pollutant NO but also produces valuable ammonia(NH_(3)).Hence,through the synthesis and modification of Fe_(3)C nanocrystal cata-lysts,the as-obtained optimal sample of Fe_(3)C/C-900 was adopted as the NORR catalyst at ambient conditions.As a result,the Fe_(3)C/C-900 catalyst showed an NH_(3)Faraday efficiency of 76.5%and an NH_(3)yield rate of 177.5μmol·h^(-1)·cm^(-2)at the working potentials of-0.8 and-1.2 V versus reversible hydrogen electrode(vs.RHE),respectively.And it delivered a stable NORR activity during the electrolysis.Moreover,we attribute the high NORR properties of Fe_(3)C/C-900 to two aspects:one is the enhanced intrinsic activity of Fe_(3)C nanocrystals,including the lowering of the energy barrier of rate-limiting step(*NOH→*N)and the inhibition of hydrogen evolution;on the other hand,the favorable dispersion of active components,the effective adsorption of gaseous NO,and the release of liquid NH_(3)products facilitated by the porous carbon substrate.
基金Supported by the National Natural Science Foundation of China,No.81000201.
文摘BACKGROUND Esophageal cancer(ESCA)is among the most prevalent and lethal tumors globally.While nitric oxide synthase 1(NOS1)is recognized for its important in-volvement in various cancers,its specific function in ESCA remains unclear.AIM To explore the potential role and underlying mechanisms of NOS1 in ESCA.METHODS Survival rates were analyzed using GeneCards and Gene Expression Profiling Interactive Analysis.The effects and mechanisms of NOS1 on ESCA cells were evaluated via the Cell Counting Kit-8 assay,scratch assay,Transwell assay,flow cytometry,quantitative polymerase chain reaction,western blotting,and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining.The protein interaction network was used to screen the interacting proteins of NOS1 and validate these interactions through co-immuno-precipitation and dual luciferase assays.Additionally,a nude mouse xenograft model was established to evaluate the effect of NOS1 in vivo.RESULTS The survival rate of patients with ESCA with high NOS1 expression was higher than that of patients with low NOS1 expression.NOS1 expression in ESCA cell lines was lower than that in normal esophageal epithelial cells.Overexpression of NOS1(oe-NOS1)inhibited proliferation,invasion,and migration abilities in ESCA cell lines,resulting in decreased autophagy levels and increased apoptosis,pyroptosis,and ferroptosis.Protein interaction studies confirmed the interaction between NOS1 and NOS1 adaptor protein(NOS1AP).Following oe-NOS1 and the silencing of NOS1AP,levels of P62 and microtubule-associated protein 1 light chain 3 beta increased both in vitro and in vivo.Furthermore,the expression levels of E-cadherin,along with the activation of phosphatidylinositol 3-kinase(PI3K)and protein kinase B(AKT),were inhibited in ESCA cell lines.CONCLUSION NOS1 and NOS1 proteins interact to suppress autophagy,activate the PI3K/AKT pathway,and exert anti-cancer effects in ESCA.
文摘Background Persistent pulmonary hypertension(PPHN)of the newborn is one of the major contributors to neonatal mortality.Current conventional treatments for PPHN primarily encompass mechanical ventilation,inhaled nitric oxide(iNO),sildenafil,and magnesium sulfate.In confirmed cases of neonatal respiratory distress syndrome,pulmonary surfactant(PS)can be considered as a potential treatment option;However,the optimal dosage and administration frequency of PS remain subjects of ongoing debate.This study aimed to assess the efficacy of early repeated endotracheal PS administration combined with iNO therapy in the management of newborns with PPHN.Methods Twenty-three neonates with PPHN received iNO alongside foundational treatments,including anti-infection therapy,mechanical ventilation,acidosis correction,and blood pressure stabilization.The observation group(n=13)received endotracheal instillation of PS three times,with each administration spaced six hours apart;The control group(n=10)received endotracheal instillation of PS once.Parameters compared included blood gas indices,oxygenation index(OI),alveolar-arterial oxygen partial pressure difference(PA-aDO,),pulmonary artery systolic pressure(PAP),and N-terminal pro-brain natriuretic peptide(NT-pro-BNP).Mechanical ventilation duration,oxygen therapy time,hospitalization length,and survival outcomes were recorded and compared between groups.Results The blood gas parameters,OI,and PA-aDO,showed no significant differences between the two groups of children before treatment(P>0.05).By 24-hour post-treatment,both groups exhibited significant increases in partial pressure of oxygen(PaO,)and potential of hydrogen(PH)levels,alongside significant decreases in lactate,partial pressure of carbon dioxide(PaCO,),OI,and PA-aDO2,with statistically significant differences(P<0.05).By 48-hour post-treatment,the observation group demonstrated significantly better improvements in blood gas parameters,OI,and PA-aDO,compared to the control group,and these differences were statistically significant(P<0.05).There was no statistically significant difference in PAP and NT-pro-BNP levels between the two groups before treatment(P>0.05).After treatment,both groups showed significant decreases in PAP and NT-pro-BNP levels(P<0.05),with a more pronounced reduction observed in the observation group(P<0.05).The observation group had significantly shorter durations of mechanical ventilation and oxygen therapy compared to the control group,with statistically significant differences(P<0.05).Additionally,the observation group exhibited a shorter total hospital stay and a lower mortality rate than the control group,though these differences were not statistically significant(P>0.05).Conclusions Early consecutive multiple doses of PS combined with iNO,compared to a single dose,better improves respiratory function indices,maintains stability,reduces pulmonary artery pressure,enhances cardiac function,shortens ventilator dependency,and increases cure rates in PPHN neonates.This approach is particularly suitable for severe PPHN cases,especially those with underlying pulmonary conditions.
基金the National Natural Science Foundation of China(22075114,32371434,82301630)the Natural Science Foundation of Jiangsu Province(BK20211034)the financial support from Jiangsu Provincial Medical Key Laboratory(Key Laboratory of Nuclear Medicine).
文摘Nitric oxide(NO)modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies.Although a nanoengineering strategy has been proposed to overcome deficiencies of NO gas or small NO donor molecules,such as short half-life,lipophilicity,non-selectivity,and poor stability,it remains challenging to prepare NO nanomedicines with simple composition,multiple functions and enhanced therapeutic efficacy.Herein,we build a liquid metal nanodroplet(LMND)-based NO nanogenerator(LMND@HSG)that is stabilized by a bioreducible guanylated hyperbranched poly(amido amine)(HSG)ligand.Mechanically,the tumor microenvironment specifically triggers a cascade process of glutathione elimination,reactive oxygen species(ROS)generation,and NO release.According to actual demand,the ROS and NO concentrations could be readily controlled by tuning the LMND and HSG feed amounts.Along with the intrinsic anticancer property of LMND(ROS-mediated apoptosis and anti-angiogenesis),LMND@HSG administration could further enhance tumor growth suppression compared with LMND and HSG alone.Fromthis study,leveraging LMND for NO gas therapy provides more possibilities for the prospect of LMND-based anticancer nanomedicines.
基金Project(U2067217)supported by the National Natural Science Foundation of ChinaProject(SASTIND)supported by the State Administration of Science,Technology and Industry for National Defense,ChinaProject(2020M683572)supported by China Postdoctoral Science Foundation。
文摘The influence of grain size or grain refinement on the corrosion of Zr alloy is clarified by employing a series of electrochemical analyses and characterization techniques.The corrosion resistance,as a function of exposure time,F−concentration,and solution temperatures,of Zr alloys with different grain sizes is ascertained.The results confirm that refining the grain size can effectively enhance the short-time corrosion properties of Zr alloy in HNO_(3) with F−.The fine grained Zr alloy(~10μm in diameter)consistently exhibits a lower corrosion current density,ranging from 18%to 46%lower than that of the coarse-grained Zr alloy(~44μm).The enhanced corrosion resistance is attributed to the high density grain boundaries,which promote oxide stability,and accelerate the creation of the protective layer.The high corrosion rate and pseudo-passivation behavior of Zr alloys in fluorinated nitric acid originate from the accelerated“dissolution-passivation”of the oxide film.However,the grain refinement does not provide enduring anti-corrosion for Zr alloys.To meet the operation of spent fuel reprocessing,additional systematic efforts are required to evaluate the long term effect of grain refinement.
基金supported by the National Natural Science Foundation of China(Nos.22171106,22431006,22150004 and 22375075)Guangdong Major Project of Basic and Applied Basic Research(Nos.2023B0303000013,2019B030302009)+1 种基金Guangdong Natural Science Foundation(No.2022A1515011937)Jinan University.
文摘The stabilization of active molecules is significantly important for chemistry,especially for the bioactive molecules.In this work,we report the synthesis and characterization of three tetrahedral Fe_(4)L_(6) cages,which are water-soluble and functionalized with or without PEG chains.All cages can physically trap NO molecules in their cavities to prevent a reaction with O_(2).Single-crystal X-ray diffraction(SCXRD),Griess assay,electron paramagnetic resonance(EPR)spectroscopy,and fluorescence assay demonstrate that NO molecules were encapsulated and stabilized by these cage molecules through the formation of host-vip supramolecules.These NO-loaded cages show high antibacterial activities for inhibiting Staphylococcus aureus and Escherichia coli,providing a convenient method for making antibiotic agents.Moreover,these PEG-functionalized cages exhibit excellent biocompatibility,providing a new strategy for developing materials for NO delivery in biomedical applications.
基金Project(2023RC3066)supported by the Science and Technology Innovation Program of Hunan Province,ChinaProject(2023JJ50079)supported by the Hunan Provincial Natural Science Foundation,China。
文摘Carbonized melamine foam has been recognized as a promising material for microwave absorption due to its exceptional thermal stability,lightweight,and remarkable dielectric properties.In this study,we investigated the impact of nitric acid oxidation on the surface of carbonized melamine foam and its microwave absorption properties.The treated foam exhibits optimal reflection loss of−21.51 dB at 13.20 GHz,with an effective absorption bandwidth of 7.04 GHz.The enhanced absorption properties are primarily attributed to the strengthened dielectric loss,improved impedance matching,and increased polarization losses resulting from the oxidized surfaces.This research demonstrates a promising new approach for research into surface treatments to improve the performances of microwave absorbers.
文摘Electrochemical nitrate reduction(eNO_(3)RR)and nitric oxide reduction(eNORR)to ammonia have emerged as promising and sustainable alternatives to the traditional Haber-Bosch method for ammonia production,particularly within the recently proposed reverse artificial nitrogen cycle route:N_(2)→NO_(x)→NH_(3).Notably,experimental studies have demonstrated that eNORR exhibits superior performance over eNO_(3)RR on Cu6Sn5 catalysts.However,the fundamental mechanisms underlying this difference remain poorly understood.Herein,we performed systematic theoretical calculations to explore the reaction pathways,electronic structure effects,and potential-dependent Faradic efficiency associated with ammonia production via these two distinct electrochemical pathways(eNORR and eNO_(3)RR)on Cu6Sn5.By implementing an advanced‘adaptive electric field controlled constant potential(EFC-CP)’methodology combined with microkinetic modeling,we successfully reproduced the experimental observations and identified the key factors affecting ammonia production in both reaction pathways.It was found that eNORR outperforms eNO_(3)RR because it circumvents the ^(*)NO_(2) dissociation and ^(*)NO_(2) desorption steps,leading to distinct surface coverage of key intermediates between the two pathways.Furthermore,the reaction rates were found to exhibit a pronounced dependence on the surface coverage of ^(*)NO in eNORR and ^(*)NO_(2) in eNO_(3)RR.Specifically,the facile desorption of ^(*)NO_(2) on the Cu6Sn5 surface in eNO_(3)RR limits the attainable surface coverage of ^(*)NO,thereby impeding its performance.In contrast,the eNORR can maintain a high surface coverage of adsorbed ^(*)NO species,contributing to its enhanced ammonia production performance.These fundamental insights provide valuable guidance for the rational design of catalysts and the optimization of reaction routes,facilitating the development of more efficient,sustainable,and scalable techniques for ammonia production.
基金The University Collaborative Innovation Project of Anhui:Creation of a Combined Animal Model of Coronary Heart Disease based on the Theory of Xin'an Medicine(No.GXXT-2020-024)Start-up Funding for Doctoral Research at Wannan Medical College(WYRCQD2018009)Horizontal Project of South Anhui Medical College(H202003)。
文摘OBJECTIVE:To explore the therapeutic effect and target of atractylenolide I(AT-I)on post-infectious irritable bowel syndrome(PI-IBS)rats.METHODS:Therefore,the preliminarily mechanism of AT-I in anti-PI-IBS were first predicted by network pharmacology and molecular docking,then the possible signaling pathways were systematically analyzed.Finally,the potential therapeutic targets and possible signaling pathways of AT-I on PI-IBS in Sprague-Dawley(SD)rat model were verified by experiments.RESULTS:AT-I could alleviate PI-IBS symptoms and reduce the expression of tumor necrosis factorα,interleukin-6 and Interferon-gamma in PI-IBS SD rat model and inhibit the c-Jun N-terminal kinase/inducible nitric oxide synthase(JNK/iNOS)pathway.Notably,AT-I treatment could inhibit the overexpression of polymeraseⅠand transcript release factor(PTRF).CONCLUSION:AT-I could alleviate PI-IBS symptoms through downregulation of PTRF and inhibiting the JNK/iNOS pathway.This study not only provides a scientific basis to clarify the anti-PI-IBS effect of AT-I and its mechanism but also suggests a novel promising therapeutic strategy to treat the PI-IBS.
文摘When the first fully expanded leaf of wheat ( Triticum aestivum L.) seedlings with two leaves were treated with different concentrations (0.05, 0.10, 0.20 and 0.50 mmol/L) of nitric oxide donor, sodium nitroprusside (SNP), the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) were reduced by the lower concentrations (0.05, 0.10 and 0.20 mmol/L), but enhanced by the higher concentration of SNP (0.50 mmol/L). The protective effect of 0.10 mmol/L SNP was the most obvious. Furthermore, the treatment with 0.10 mmol/L SNP on the above seedlings until the fourth leaves were fully expanded attenuated the accumulation of H2O2, superoxide anion radical (O-2(-)) and MDA, also counteracted the degradation of chlorophyll and soluble proteins, especally Rubisco, both leading to the effective delay of aging process in wheat leaves. The effects of different SNP concentrations (0.05, 0.10, 0.20, 0.50, 1.00 and 5.00 mmol/L) also displayed a dual role in an aging experiment of chloroplasts in vitro, one of which, 0.2 mmol/L SNP treatment, protected the membrane structure and attenuated the degradation of Rubisco effectively. Based on the present results, it was inferred that lower concentrations of nitric oxide (NO) might play a role in delaying aging process in wheat leaves, i.e., might attribute to decrease the level of reactive oxygen species (ROS) and the alleviation of further oxidative damage caused by ROS.
基金The National High Technology Research Program of China (863 Program) (No. 2008AA05Z303)the Science and Technology Program of Jiangsu Province (No. BE2010184)the Environmental Protection Scientific Research Subject of Jiangsu Province (No.201031)
文摘In order to remove nitric oxides (NO) from flue gas, experimental studies on the photocatalytic oxidation (PCO) of NO are carried out in an efficient laboratory-scale reactor. Nano-sized TiO2 particles loading on quartz sand are prepared and used as the photocatalyst. Effects of several key operating parameters on NO conversion are investigated, including operating temperature, NO inlet concentration, oxygen percentage, relative humidity and residence time. The results illustrate that the NO inlet concentration, the oxygen percentage and the relative humidity play an important role in the oxidation of NO. A lower NO inlet concentration and a higher oxygen percentage result in a higher NO conversion efficiency. When the relative humidity is 8%, the maximum value of NO conversion efficiency is achieved. In addition, the operating temperature and the residence time have a little effect on the conversion efficiency of NO.
文摘Effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on the germination and metabolism of reactive oxygen species were surveyed in wheat (Triticum aestivum L.) seeds. Germination of wheat seeds and even the elongation of radicle and plumule were dramatically promoted by SNP treatments during the germination under osmotic stress. Meanwhile, activities of amylase and EP were enhanced, thus leading to the degradation of storage reserve in seeds. After osmotic stress was removed, higher viability of wheat seeds was also maintained. In addition, the activities of CAT, APX and the content of proline were increased by SNP treatment simultaneously, but activities of LOX were inhibited, and both of which were beneficial for improving the antioxidant capacity during the germination of wheat seeds under osmotic stress. It was also shown that the increase of the activity of amylase induced by SNP in embryoless half-seeds of wheat in the beginning period of germination (6 h) might be indirectly related to GA(3).
基金supported by the National Natural Science Foundation of China(No. 30971021,81030023 and 30901550)
文摘Neuronal nitric oxide synthase (nNOS) is mainly expressed in neurons,to some extent in astrocytes and neuronal stem cells.The alternative splicing of nNOS mRNA generates 5 isoforms of nNOS,including nNOS-,nNOS-,nNOS-,nNOS-and nNOS-2.Monomer of nNOS is inactive,and dimer is the active form.Dimerization requires tetrahydrobiopterin (BH 4),heme and L-arginine binding.Regulation of nNOS expression relies largely on cAMP response element-binding protein (CREB) activity,and nNOS activity is regulated by heat shock protein 90 (HSP90)/HSP70,calmodulin (CaM),phosphorylation and dephosphorylation at Ser847 and Ser1412,and the protein inhibitor of nNOS (PIN).There are primarily 9 nNOS-interacting proteins,including post-synaptic density protein 95 (PSD95),clathrin assembly lymphoid leukemia (CALM),calcium/calmodulindependent protein kinase II alpha (CAMKIIA),Disks large homolog 4 (DLG4),DLG2,6-phosphofructokinase,muscle type (PFK-M),carboxy-terminal PDZ ligand of nNOS (CAPON) protein,syntrophin and dynein light chain (LC).Among them,PSD95,CAPON and PFK-M are important nNOS adapter proteins in neurons.The interaction of PSD95 with nNOS controls synapse formation and is implicated in N-methyl-D-aspartic acid-induced neuronal death.nNOS-derived NO is implicated in synapse loss-mediated early cognitive/motor deficits in several neuropathological states,and negatively regulates neurogenesis under physiological and pathological conditions.
基金Supported by National Natural Science Foundation of China(No.30671061)Natural Science Foundation of Shanxi Province(No.2008011059-1 and No.20041101)~~
文摘[Objective] Effects of different concentrations of nitric oxide on membrane lipid peroxidation of wheat induced by enhanced UV-B radiation were researched,sodium nitroprusside (SNP) was selected as an exogenous nitric oxide(NO)donor.[Method] There are 3 groups including CK,UV treatment group (B),B+SNP treatment group,0,1,2,3,4 d sampling after treatment respectively,and physiological and biochemical indexes of MDA content and CAT,POD,SOD and so on were determined,repeated 3 times,and statistical analyzed.[Result] The results showed that,after the enhanced UV-B radiation,activity of the catalase (CAT),superoxide dismutase (SOD) and of the guaiacol peroxidase (POD) all reduced apparently,and the concentration of malondialdehyde (MDA) increased obviously,leading to oxidative damage in wheat seedlings.Impose different concentrations of SNP after UV-B radiation,may mitigate oxidative damage of wheat seedling from different degrees,which was in agreement with the effect of making the concentration of MDA decrease and the activity of the CAT,SOD and POD all increased.The mitigation role of 0.01 mol/L SNP was more obvious for roots' oxidative damage,while 0.1 mmol/L SNP is more effective for oxidative damage of leaves.[Conclusion] Exogenous NO donor SNP had obvious relieve effects on oxidative damage of wheat seedlings caused by UV-B radiation,which can enhance adaptive capacity of plants to adversity stress.
文摘Objective: To investigate the role of PKC isoforms in the regulation of LPS-triggered tumoricidal activity in macrophages and further elucidate its signal mechanisms. Methods: Two macrophage cell lines (P388D1 and RAW264.7) were stimulated by LPS alone, or with long-term of PMA pretreatment. Then cytotoxicities to P815 cells (by MTT assay) and IL-1, TNF- (by ELISA) and nitric oxide (NO) production (by Griess reagent) in supernatants were measured. Western blot for PKC isoforms after long-term PMA pretreatment was analyzed. Results: RAW264.7 cells were stimulated with LPS to kill target tumor cells P815, whereas P388D1 cells failed to develop such an ability. Down-regulation of PKC isoforms by chronic treatment with PMA significantly inhibited the LPS-induced cytotoxicity in RAW264.7 cells. In unstimulated state, Western blotting with rabbit antiserum specific for the PKC, 1, 2, or showed all 5 isoforms were detected in P388D1 cells, while only PKC, PKC1 and PKC were detected in RAW264.7 cells. Exposure of the cells to long-term of PMA treatment significantly down-regulated the expression of PKC, PKC1 and PKC in RAW264.7 cells. But in P388D1 cells, although PKC, PKC and PKC were down-regulated, the expression of PKC1 and PKC2 could not be regulated. Comparing with LPS-induced IL-1, TNF- and NO production by the two macrophage cell lines, P388D1 failed to produce NO. In RAW264.7 cells, LPS-induced NO production and antitumor activity was attenuated by the addition of L-NAME, an iNOS inhibitor. Conclusion: The results indicated a critical role of PKC in LPS-induced antitumor activity and this cytotoxicity is mainly due to PKC- mediated NO production by RAW264.7 cells, but not a direct cytotoxic activity.
文摘Objective To investigate the effect of nitric oxide (NO) on the expression of apelin receptor mRNA, as well as their correlation, in the caudate nucleus of rat. Methods L-Arginine (L-Arg), N^G-nitro-L-arginine methyl ester (L-NAME) and normal saline (NS) was separately microinjected into rat caudate nucleus. Expressions of neuronal NO synthase (nNOS) mRNA and apelin receptor mRNA were detected by RT-PCR at 4, 8, 12, 24 and 48 h after microinjection, and their correlation was determined. Results The expressions of nNOS mRNA and apelin receptor mRNA were both significantly increased after microinjection of L-Arg, but significantly decreased after microinjection of L-NAME compared with the NS control group. The nNOS mRNA had a positive correlation with the expression of apelin receptor mRNA after microinjection of L-Arg and L-NAME. Conclusion The activity of NOS in the central nervous system, especially in the caudate nucleus, is one of the key factors for NO to exert many kinds of biological actions, such as modulation of central pain, as a neurotransmitter. The neurobiological action of NO in rat caudate nucleus may be associated with apelin receptors.