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
It was demonstrated that xanthine oxidoreductase (XOR), during ischemia, catalyzes the formation of nitric oxide (NO) from nitrite (NO_2^-) and this NO_2^--derived NO protects the isolated perfused rat heart against t...It was demonstrated that xanthine oxidoreductase (XOR), during ischemia, catalyzes the formation of nitric oxide (NO) from nitrite (NO_2^-) and this NO_2^--derived NO protects the isolated perfused rat heart against the damaging effects of ischemia-reperfusion (I/R) when conventional nitric oxide synthase (NOS) -dependent NO production is impaired. Liver is one of the organs with the highest XOR concentration. This study was designed to determine whether NO_2^--derived NO by XOR protects liver against I/R injury in vivo. For its minute amounts and active reactivity, NO can not be detected directly in real time in vivo by this time. We have to prove the above hypothesis indirectly. METHODS:Wistar rats were pretreated with saline, NOS inhibitor L-NAME (10 mg/kg intravenously), XOR inhibitor allopurinol (1.5 mg/kg orally), L-NAME +allopurinol and NO scavenger carboxy-PTIO (0.6 mg/kg intravenously) respectively (12 animals per group). And then, they were subjected to total liver ischemia for 40 minutes followed by reperfusion. Blood samples and liver tissues were obtained for analysis after 3 hours of reperfusion. Survival was also investigated. RESULTS:Allopurinol-treated animals exhibited further increased serum alanine aminotransferase (ALT) levels and liver myeloperoxidase (MPO) activities, but further decreased liver adenosine triphosphate (ATP) stores after I/R compared to saline-treated counterparts (830.5±108.3 U/L, 56.5±11.0 U/mg protein and 1.93±0.47 μmol/g vs. 505.8± 184.2 U/L, 41.5±10.2 U/mg protein and 3.05±0.55 μmol/g respectively, P<0.01, P<0.05 and P<0.01 respectively). The hepatocyte injury was further exacerbated and the overall survival rate was significantly decreased after I/R in animals given by allopurinol compared to those pretreated by saline (P<0.05). L-NAME and allopurinol co-treated animals exhibited more severe liver injury (P<0.05 and P<0.01) and a further decreased overall survival rate (P<0.05) compared to L-NAME or allopurinol alone-treated counterparts, but they were not different from carboxy-PTIO treated animals (P>0.05). CONCLUSION:NO_2^--derived NO by XOR in the hypoxic and acidic environment induced by hepatic I/R protects the liver against I/R injury in vivo.展开更多
The effects of an exogenous nitric oxide donor(sodium nitroprusside, SNP), a NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxode(PTIO) and carboxy-PTIO potassium salt(c PTIO) on the embryo germination ...The effects of an exogenous nitric oxide donor(sodium nitroprusside, SNP), a NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxode(PTIO) and carboxy-PTIO potassium salt(c PTIO) on the embryo germination of Sorbus pohuashanensis were studied in a petri dish test. SNP at 0.5–5 mmol L-1 increased germination percentage, mean time to germination, germination index and germination energy compared with the control to different degrees. Treatment with 2 mmol L-1 SNP improved germination most significantly; embryo germination percentage for mother tree 1(91.11%) and mother tree 2(64.44%) were much higher than the control. In addition,excessive SNP levels did not enhance embryo germination.Combined treatment with SNP and an NO scavenger delayed embryo germination. Treatment with c PTIO inhibited embryo germination; germination percentage was 42.22% and was lower than that of the control. These results show that low concentrations of exogenous NO can enhance the embryo germination of S. pohuashanensis,providing a simple, effective way for promoting germination of S. pohuashanensis.展开更多
Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug...Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are still unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cellular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/ tyrosine kinase activity is able to modulate cell signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebellum and liver of the same animals. We demonstrated that atorvastatin treatment (80 mg/day for 14.5 months) to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebellum. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as well as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not associated with higher oxidative/nitrosative stress levels. We hypothesize that biliverdin reductase-A-dependent inducible nitric oxide synthase regulation strongly contributes to the cognitive improvement observed following atorvastatin treatment.展开更多
During wet complexation denitrification of flue gas,Fe^(Ⅱ)EDTA regeneration,also known as reducing Fe^(Ⅱ)EDTA and Fe^(Ⅱ)EDTA-nitric oxide(NO)to Fe^(Ⅱ)EDTA,is crucial.In this paper,ultraviolet(UV)light was used for...During wet complexation denitrification of flue gas,Fe^(Ⅱ)EDTA regeneration,also known as reducing Fe^(Ⅱ)EDTA and Fe^(Ⅱ)EDTA-nitric oxide(NO)to Fe^(Ⅱ)EDTA,is crucial.In this paper,ultraviolet(UV)light was used for the first time to reduce Fe^(Ⅱ)EDTA-NO.The experimental result demonstrated that Fe^(Ⅱ)EDTA-NO reduction rate increased with UV power increasing,elevated temperature,and initial Fe^(Ⅱ)EDTA-NO concentration decreasing.Fe^(Ⅱ)EDTA-NO reduction rate increased first and then decreased as pH value increased(2.0-10.0).Fe^(Ⅱ)EDTA-NO reduction with UV irradiation presented a first order reaction with respect to Fe^(Ⅱ)EDTA-NO.Compared with other Fe^(Ⅱ)EDTA regeneration methods,Fe^(Ⅱ)EDTA regeneration with UV show more superiority through comprehensive consideration of regeneration rate and procedure.Subsequently,NO absorption experiment by Fe^(Ⅱ)EDTA solution with UV irradiation confirmed that UV can significantly promote the NO removal performance of Fe^(Ⅱ)EDTA.Appropriate oxygen concentration(3%(vol))and acidic environment(pH=4)was favorable for NO removal.With UV power increasing as well as temperature decreasing,NO removal efficiency rose.In addition,the mechanism research indicates that NO from flue gas is mostly converted to NO_(2)-,NO_(3)-,NH_(4)^(+),N_(2),and N_(2)O with Fe^(Ⅱ)EDTA absorption liquid with UV irradiation.UV strengthens NO removal in Fe^(Ⅱ)EDTA absorption liquid by forming a synergistic effect of oxidation-reduction-complexation.Finally,compared with NO removal methods with Fe^(Ⅱ)EDTA,Fe^(Ⅱ)EDTA combined UV system shows prominent technology advantage in terms of economy and secondary pollution.展开更多
Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to expl...Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.展开更多
Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in mo...Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in modulating the plant’s response to iron deficiency.Iron deficiency leads to an increase in the activity of heme oxygenase(HO)and the subsequent generation of CO.Additionally,it alters the polar subcellular distribution of Pin-Formed 1(PIN1)proteins,resulting in enhanced auxin transport.This alteration,in turn,leads to an increase in NO accumulation.Furthermore,iron deficiency enhances the activity of ferric chelate reductase(FCR),as well as the expression of the Fer-like iron deficiency-induced transcription factor 1(FIT)and the ferric reduction oxidase 2(FRO2)genes in plant roots.Overexpression of the long hypocotyl 1(HY1)gene,which encodes heme oxygenase,or the CO donor treatment resulted in enhanced basipetal auxin transport,higher FCR activity,and the expression of FIT and FRO2 genes under Fe deficiency.Here,a potential mechanism is proposed:CO and NO interact with auxin to address iron deficiency stress.CO alters auxin transport,enhancing its accumulation in roots and up-regulating key iron-related genes like FRO2 and IRT1.Elevated auxin levels affect NO signaling,leading to greater sensitivity in root development.This interplay promotes FCR activity,which is crucial for iron absorption.Together,these molecules enhance iron uptake and root growth,revealing a novel aspect of plant physiology in adapting to environmental stress.展开更多
BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as com...BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as complications and adverse outcomes persist.Incorporating humanized nursing modes and novel treatments like nitric oxide inhalation may enhance recovery and reduce postoperative complications.AIM To evaluate the effects of a humanized nursing mode combined with nitric oxide inhalation on the rehabilitation outcomes of patients undergoing lung surgery,focusing on pulmonary function,recovery speed,and overall treatment costs.METHODS A total of 79 patients who underwent lung surgery at a tertiary hospital from March 2021 to December 2021 were divided into a control group(n=39)receiving a routine nursing program and an experimental group(n=40)receiving additional humanized nursing interventions and atomized inhalation of nitric oxide.Key indicators were compared between the two groups alongside an analysis of treatment costs.RESULTS The experimental group demonstrated significant improvements in pulmonary function,reduced average recovery time,and lower total treatment costs compared to the control group.Moreover,the quality of life in the experimental group was significantly better in the 3 months post-surgery,indicating a more effective rehabilitation process.CONCLUSION The combination of humanized nursing mode and nitric oxide inhalation in postoperative care for lung surgery patients significantly enhances pulmonary rehabilitation outcomes,accelerates recovery,and reduces economic burden.This approach offers a promising reference for improving patient care and rehabilitation efficiency following lung surgery.展开更多
Stavudine, a potent anti HIV and AIDS related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcript...Stavudine, a potent anti HIV and AIDS related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcriptase by acting as a false substrate. Modifications made on the hydrogen labile at the 5' position on the sugar is an interesting template for the elaboration of new potent anti HIV and AIDS drugs. The expected advantages of the modified stavudine prodrugs can be multiple: synergistic drug activities, enhancement of stavudine intracellular uptake, increase of stavudine brain delivery, and bypass of the first stavudine phosphorylation step into the cells. Nitric oxide synthase inhibitors of stavudine and nitric oxide donors of stavudine may hold significant promise for the treatment of HIV and AIDS.展开更多
Nitric oxide (NO) has been implicated in the promotion of neurodegeneration. However, little is known about the relationship between NO and the self-renewal or differentiation capacity of neural stem cells (NSCs) ...Nitric oxide (NO) has been implicated in the promotion of neurodegeneration. However, little is known about the relationship between NO and the self-renewal or differentiation capacity of neural stem cells (NSCs) in neurodegenerative disease. In this study, we investigated the effect of NO on self-renewal of NSCs in an animal model for Niemann-Pick type C (NPC) disease. We found that NO production was significantly increased in NSCs from NPCl-deficient mice (NPCI^-/-), which showed reduced NSC self-renewal. The number of nestin-positive cells and the size of neurospheres were both significantly decreased. The expression of NO synthase (NOS) was increased in neurospheres derived from the brain of NPC1^-/- mice in comparison to wild-type neurospheres. NO-mediated activation of glycogen synthase ki- nase-3β (GSK3β) and caspase-3 was also observed in NSCs from NPC1^-/- mice. The self-renewal ability of NSCs from NPC1^-/- mice was restored by an NOS inhibitor, L-NAME, which resulted in the inhibition of GSK3β and caspase-3. In addition, the differentiation ability of NSCs was partially restored and the number of Fluoro-Jade C-positive degenerating neurons was reduced. These data suggest that overproduction of NO in NPC disease impaired the self-renewal of NSCs. Control of NO production may be key for the treatment of NPC disease.展开更多
AIM:To clarify whether the vasoconstrictory response is impaired and to study vascular function in patients with migraine during the headache attack.METHODS:We studied vascular reactivity in the resistance arteries by...AIM:To clarify whether the vasoconstrictory response is impaired and to study vascular function in patients with migraine during the headache attack.METHODS:We studied vascular reactivity in the resistance arteries by using the forearm perfusion technique associated with plethysmography.We measuredforearm blood flow by strain-gauge plethysmography during intra-brachial infusion of acetylcholine,sodium nitroprusside or norepinephrine in 11 controls and 13patients with migraine,11 of them(M) in the interval between the migraine attacks and 4 during a headache attack(MH).Written informed consent was obtained from patients and healthy controls,and the study was approved by the Ethics Committee of the University Federico Ⅱ.RESULTS:Compared to healthy control subjects,in patients with migraine studied during the interictal period,the vasodilating effect of acetylcholine,that acts through the stimulation of endothelial cells and the release of nitric oxide,was markedly reduced,but became normal during the headache attack(P<0.05by analysis of variance).The response to nitroprusside,which directly relaxes vascular smooth muscle cells(VSMCs),was depressed in patients with migraine studied during the interictal period,but normal during the headache attack(P<0.005).During norepinephrine infusion,forearm blood flow decreased in control subjects(-40% ± 5%,P<0.001).In contrast,in patients with migraine,either when studied during or free of the headache attack forearm blood flow did not change compared to the baseline value(-3%±13% and-10.4%±15%,P>0.05).CONCLUSION:In migrainers,the impaired relaxation of VSMCs is restored during the headache attack.The vasoconstrictory response is impaired and remains unchanged during the migraine attack.展开更多
OBJECTIVE To investigate the regulation of {O^2(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate}(JS-K),anitric oxide donor,on tumor energy metabolism in H22 tumor-bearing mice.METHODS Th...OBJECTIVE To investigate the regulation of {O^2(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate}(JS-K),anitric oxide donor,on tumor energy metabolism in H22 tumor-bearing mice.METHODS The hepatoma animal model in BALB/c mice was established with H22 cell line.The JS-K group and model group were received JS-K(0.75 and 1.5 mg?kg^(-1)) and saline via tail intravenous once every 3 d for 14 d,received 5 injections,respectively.The positive group was received 5-FU 20 mg·kg^(-1) by intraperitoneal injection once a day for 14 d.On the 15 th day mice were sacrificed.The tumor growth inhibition rate were calculated.The activities of hexokinase(HK),phosphofructo kinase(PFK),pyruvate kinase(PK),succinate dehydrogenase(SDH),adenosine triphosphatase(ATPase),and the levels of lactic acid(LD) and adenosine triphosphate(ATP) in tumor tissues were determined by colorimetric method.RESULTS Compared with model group,the tumor mass of JS-K0.75 and 1.5 mg·kg^(-1) group was significantly reduced(P<0.01),and the tumor growth inhibition rate was 23.9% and 50.3%,respectively.The activity of HK,PFK,PK,SDH and ATPase of tumor tissue in model group was(22.6±3.7,14.4±2.6,12.9±3.2 and 10.5±2.6)U·g^(-1) protein and(0.70±0.10)μmol Pi·mg^(-1) protein per hour,respectively;which in JS-K 1.5 mg?kg^(-1) group was dropped by 42.0%,26.6%,22.7%,23.3% and 21.7%(P<0.01,P<0.05).Compared with the model group,the level of ATP and LD in JS-K group was dropped(P<0.01).CONCLUSION JS-K can inhibit the growth of tumor in H22 tumor-bearing mice and its mechanism may be related to regulating the tumor energy metabolism with inhibition of glycolysis and aerobic oxidation.展开更多
AIM: To clarify how the endothelial nitric oxide synthase (eNOS, NOS3) make effect on outflow facility through the trabecular meshwork (TM). METHODS: Inhibition of NOS3 gene expression in human TM cells were co...AIM: To clarify how the endothelial nitric oxide synthase (eNOS, NOS3) make effect on outflow facility through the trabecular meshwork (TM). METHODS: Inhibition of NOS3 gene expression in human TM cells were conducted by three siRNAs. Then the mRNA and protein levels of NOS3 in siRNA-treated and negative control (NC) cells were determined, still were the collagen, type IV, alpha 1 (COL4A1) and fibronectin 1 by real-time PCR and Western blot analysis. In addition, NOS3 concentrations in culture supernatant fluids of TM cells were measured. Cell cycle and cell apoptosis analysis were performed using flow cytometry. RESULTS: The mRNA level of NOS3 was decreased by three different siRNA interference, similar results were obtained not only of the relative levels of NOS3 protein, but also the expression levels of COL4A1 and fibronectin 1. The number of cells in S phase was decreased, while contrary result was obtained in G2 phase. The number of apoptotic cells in siRNA-treated groups were significant increased compared to the NC samples. CONCLUSION: Abnormal NOS3 expression can make effects on the proteins levels of extracellular matrix component (e.g. fibronectin 1 and COL4A1). Reduced NOS3 restrains the TM cell cycle progression at the G2/ M-phase transition and induced cell apoptosis.展开更多
R Nitric oxide probably plays an important role in mechanisms determining sexual dimorphism in the development of cardiovascular diseases, including hypertension. Because stress together with gender are significant ca...R Nitric oxide probably plays an important role in mechanisms determining sexual dimorphism in the development of cardiovascular diseases, including hypertension. Because stress together with gender are significant cardiovascular risk factors, we studied the role nitric oxide in car-diovascular regulation in male and female nor-motensive and hypertensive rats under normal and stress conditions. Experiments were per-formed in mongrel normotensive and hyperten-sive (two kidney, one clip) rats of both sexes, weighing 200-250g. The study of mean arterial pressure and heart rate was carried out: 1) under control condition;2) during nitric oxide blo- ckade by NG-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg, iv) 3) during 60 min immobilization stress and recovery;4) during 60 min immobi-lization stress + L-NAME and recovery. We found that the severity of hypertension in fe-males was lower than in males. We also ob-served that both normotensive and hyperten-sive females demonstrated more favorable pat-tern of cardiovascular responses to stress. At rest, nitric oxide blockade increased the mean arterial pressure and decreased the heart rate more effectively in female normotensive and hypertensive rats than in male groups. During stress, nitric oxide blockade modified the stress- induced cardiovascular responses more sig-nificantly in female normotensive and hyper-tensive rats compared with male groups. Our data show that both normotensive and hyper-tensive females demonstrated the more effec-tive nitric oxide control of cardiovascular activ-ity under normal and especially stress condi-tions than male groups. This male-female dif-ference may be important mechanism respon-sible for greater in females vs. males of cardio-vascular resistance to stress and development of hypertension.展开更多
AIM: To assess whether a liver specific nitric oxide (NO) donor (V-PYRRO/NO) would prevent the development of portal hypertension and liver fibrosis in rats with bile duct ligation (BDL). METHODS: Treatment (placebo o...AIM: To assess whether a liver specific nitric oxide (NO) donor (V-PYRRO/NO) would prevent the development of portal hypertension and liver fibrosis in rats with bile duct ligation (BDL). METHODS: Treatment (placebo or V-PYRRO/NO 0.53 μmol/kg per hour) was administered i.v. to rats 2 d before BDL (D-2) and maintained until the day of hemodynamic measurement (D26). Intra-hepatic NO level was estimated by measuring liver cGMP level. Effects of V-PYRRO/NO on liver fibrosis and lipid peroxidation were also assessed. RESULTS: Compared to placebo treatment, V-PYRRO/ NO improved splanchnic hemodynamics in BDL rats: portal pressure was significantly reduced by 27% (P < 0.0001) and collateral circulation development was almost completely blocked (splenorenal shunt blood flow by 74%, P = 0.007). Moreover, V-PYRRO/NO significantly prevented liver fibrosis development in BDL rats (by 30% in hepatic hydroxyproline content and 31% in the area of fibrosis, P < 0.0001 respectively), this effect being probably due to a decrease in lipid peroxidation by 44% in the hepatic malondialdehyde level (P = 0.007). Interestingly, we observed a significant and expected increase in liver cGMP, without any systemic hemodynamic effects (mean arterial pressure, vascular systemic resistance and cardiac output) in both sham- operated and BDL rats treated with V-PYRRO/NO. This result is in accordance with studies on V-PYRRO/NO metabolism showing a specific release of NO in the liver.NO in BDL rats improved liver fibrosis and splanchnic hemodynamics without any noxious systemic hemo- dynamic effects.展开更多
Background: The ideal agent for cervical ripening would induce adequate cervical ripening with minimal adverse effects to the mother and the fetus;the most favorable method for cervical ripening is not fully agreed ti...Background: The ideal agent for cervical ripening would induce adequate cervical ripening with minimal adverse effects to the mother and the fetus;the most favorable method for cervical ripening is not fully agreed till now;however, vaginal administration of isosorbide mononitrate (IMN) is considered a low-risk method of labor induction for post term. Our study was designed to assess the effect of IMN on cervical ripening and labor induction among 41 weeks pregnant women. Objectives: To assess the efficacy of the nitric oxide donor isosorbide mononitrate on cervical ripening at 41 weeks gestation. Materials and Methods: This study was conducted on 100 pregnant women recruited from the outpatient clinic fulfilling the inclusion criteria. Cases were divided into 2 groups. In first group 40 mg isosorbide mononitrate (IMN) tablet was applied vaginally in posterior fornix, and in second group placebo was applied vaginally in posterior fornix. Following up the cervical status after 24 hours of administration, the patient were asked about new symptoms especially headache, palpitation, dizziness or abdominal pain and the mode of delivery was assessed. Results: There was a significant improvement in the bishop score in the first group rather than the placebo group. No significant difference between the two groups was as regards the mode of delivery. Conclusion: IMN may be used for cervical preparation only before induction of labor in post term cases.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
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
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
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.
文摘It was demonstrated that xanthine oxidoreductase (XOR), during ischemia, catalyzes the formation of nitric oxide (NO) from nitrite (NO_2^-) and this NO_2^--derived NO protects the isolated perfused rat heart against the damaging effects of ischemia-reperfusion (I/R) when conventional nitric oxide synthase (NOS) -dependent NO production is impaired. Liver is one of the organs with the highest XOR concentration. This study was designed to determine whether NO_2^--derived NO by XOR protects liver against I/R injury in vivo. For its minute amounts and active reactivity, NO can not be detected directly in real time in vivo by this time. We have to prove the above hypothesis indirectly. METHODS:Wistar rats were pretreated with saline, NOS inhibitor L-NAME (10 mg/kg intravenously), XOR inhibitor allopurinol (1.5 mg/kg orally), L-NAME +allopurinol and NO scavenger carboxy-PTIO (0.6 mg/kg intravenously) respectively (12 animals per group). And then, they were subjected to total liver ischemia for 40 minutes followed by reperfusion. Blood samples and liver tissues were obtained for analysis after 3 hours of reperfusion. Survival was also investigated. RESULTS:Allopurinol-treated animals exhibited further increased serum alanine aminotransferase (ALT) levels and liver myeloperoxidase (MPO) activities, but further decreased liver adenosine triphosphate (ATP) stores after I/R compared to saline-treated counterparts (830.5±108.3 U/L, 56.5±11.0 U/mg protein and 1.93±0.47 μmol/g vs. 505.8± 184.2 U/L, 41.5±10.2 U/mg protein and 3.05±0.55 μmol/g respectively, P<0.01, P<0.05 and P<0.01 respectively). The hepatocyte injury was further exacerbated and the overall survival rate was significantly decreased after I/R in animals given by allopurinol compared to those pretreated by saline (P<0.05). L-NAME and allopurinol co-treated animals exhibited more severe liver injury (P<0.05 and P<0.01) and a further decreased overall survival rate (P<0.05) compared to L-NAME or allopurinol alone-treated counterparts, but they were not different from carboxy-PTIO treated animals (P>0.05). CONCLUSION:NO_2^--derived NO by XOR in the hypoxic and acidic environment induced by hepatic I/R protects the liver against I/R injury in vivo.
基金supported by the Science Foundation of Heilongjiang Province of China(C201407)the National Natural Science Foundation of China(No.31400535)
文摘The effects of an exogenous nitric oxide donor(sodium nitroprusside, SNP), a NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxode(PTIO) and carboxy-PTIO potassium salt(c PTIO) on the embryo germination of Sorbus pohuashanensis were studied in a petri dish test. SNP at 0.5–5 mmol L-1 increased germination percentage, mean time to germination, germination index and germination energy compared with the control to different degrees. Treatment with 2 mmol L-1 SNP improved germination most significantly; embryo germination percentage for mother tree 1(91.11%) and mother tree 2(64.44%) were much higher than the control. In addition,excessive SNP levels did not enhance embryo germination.Combined treatment with SNP and an NO scavenger delayed embryo germination. Treatment with c PTIO inhibited embryo germination; germination percentage was 42.22% and was lower than that of the control. These results show that low concentrations of exogenous NO can enhance the embryo germination of S. pohuashanensis,providing a simple, effective way for promoting germination of S. pohuashanensis.
基金Funding for the canine atorvastatin study was through the Alzheimer's Association IIRG-03-5673 to Elizabeth Head
文摘Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are still unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cellular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/ tyrosine kinase activity is able to modulate cell signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebellum and liver of the same animals. We demonstrated that atorvastatin treatment (80 mg/day for 14.5 months) to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebellum. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as well as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not associated with higher oxidative/nitrosative stress levels. We hypothesize that biliverdin reductase-A-dependent inducible nitric oxide synthase regulation strongly contributes to the cognitive improvement observed following atorvastatin treatment.
基金supported by National Natural Science Foundation of China(52260012)Natural Science Foundation of Jiangxi Province(20232BAB203053,20212ACB213001,20232BAB203033)+1 种基金General Project of Jiangxi Province Key Research and Development Program(20192BBG70008)Training Plan for Academic and Technical Leaders of Major Disciplines in Jiangxi Province-youth Talent Project(20232BCJ23047).
文摘During wet complexation denitrification of flue gas,Fe^(Ⅱ)EDTA regeneration,also known as reducing Fe^(Ⅱ)EDTA and Fe^(Ⅱ)EDTA-nitric oxide(NO)to Fe^(Ⅱ)EDTA,is crucial.In this paper,ultraviolet(UV)light was used for the first time to reduce Fe^(Ⅱ)EDTA-NO.The experimental result demonstrated that Fe^(Ⅱ)EDTA-NO reduction rate increased with UV power increasing,elevated temperature,and initial Fe^(Ⅱ)EDTA-NO concentration decreasing.Fe^(Ⅱ)EDTA-NO reduction rate increased first and then decreased as pH value increased(2.0-10.0).Fe^(Ⅱ)EDTA-NO reduction with UV irradiation presented a first order reaction with respect to Fe^(Ⅱ)EDTA-NO.Compared with other Fe^(Ⅱ)EDTA regeneration methods,Fe^(Ⅱ)EDTA regeneration with UV show more superiority through comprehensive consideration of regeneration rate and procedure.Subsequently,NO absorption experiment by Fe^(Ⅱ)EDTA solution with UV irradiation confirmed that UV can significantly promote the NO removal performance of Fe^(Ⅱ)EDTA.Appropriate oxygen concentration(3%(vol))and acidic environment(pH=4)was favorable for NO removal.With UV power increasing as well as temperature decreasing,NO removal efficiency rose.In addition,the mechanism research indicates that NO from flue gas is mostly converted to NO_(2)-,NO_(3)-,NH_(4)^(+),N_(2),and N_(2)O with Fe^(Ⅱ)EDTA absorption liquid with UV irradiation.UV strengthens NO removal in Fe^(Ⅱ)EDTA absorption liquid by forming a synergistic effect of oxidation-reduction-complexation.Finally,compared with NO removal methods with Fe^(Ⅱ)EDTA,Fe^(Ⅱ)EDTA combined UV system shows prominent technology advantage in terms of economy and secondary pollution.
基金financially supported by the National Natural Science Foundation of China(82101069,82102537,82160411,82002278)the Natural Science Foundation of Chongqing Science and Technology Commission(CSTC2021JCYJ-MSXMX0170,CSTB2022BSXM-JCX0039)+2 种基金the First Affiliated Hospital of Chongqing Medical University Cultivating Fund(PYJJ2021-02)the Beijing Municipal Science&Technology Commission(Z221100007422130)the Youth Incubation Program of Medical Science and Technology of PLA(21QNPY116).
文摘Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.
基金Open Project of Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake,Grant Number HZHLAB2201.
文摘Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in modulating the plant’s response to iron deficiency.Iron deficiency leads to an increase in the activity of heme oxygenase(HO)and the subsequent generation of CO.Additionally,it alters the polar subcellular distribution of Pin-Formed 1(PIN1)proteins,resulting in enhanced auxin transport.This alteration,in turn,leads to an increase in NO accumulation.Furthermore,iron deficiency enhances the activity of ferric chelate reductase(FCR),as well as the expression of the Fer-like iron deficiency-induced transcription factor 1(FIT)and the ferric reduction oxidase 2(FRO2)genes in plant roots.Overexpression of the long hypocotyl 1(HY1)gene,which encodes heme oxygenase,or the CO donor treatment resulted in enhanced basipetal auxin transport,higher FCR activity,and the expression of FIT and FRO2 genes under Fe deficiency.Here,a potential mechanism is proposed:CO and NO interact with auxin to address iron deficiency stress.CO alters auxin transport,enhancing its accumulation in roots and up-regulating key iron-related genes like FRO2 and IRT1.Elevated auxin levels affect NO signaling,leading to greater sensitivity in root development.This interplay promotes FCR activity,which is crucial for iron absorption.Together,these molecules enhance iron uptake and root growth,revealing a novel aspect of plant physiology in adapting to environmental stress.
文摘BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as complications and adverse outcomes persist.Incorporating humanized nursing modes and novel treatments like nitric oxide inhalation may enhance recovery and reduce postoperative complications.AIM To evaluate the effects of a humanized nursing mode combined with nitric oxide inhalation on the rehabilitation outcomes of patients undergoing lung surgery,focusing on pulmonary function,recovery speed,and overall treatment costs.METHODS A total of 79 patients who underwent lung surgery at a tertiary hospital from March 2021 to December 2021 were divided into a control group(n=39)receiving a routine nursing program and an experimental group(n=40)receiving additional humanized nursing interventions and atomized inhalation of nitric oxide.Key indicators were compared between the two groups alongside an analysis of treatment costs.RESULTS The experimental group demonstrated significant improvements in pulmonary function,reduced average recovery time,and lower total treatment costs compared to the control group.Moreover,the quality of life in the experimental group was significantly better in the 3 months post-surgery,indicating a more effective rehabilitation process.CONCLUSION The combination of humanized nursing mode and nitric oxide inhalation in postoperative care for lung surgery patients significantly enhances pulmonary rehabilitation outcomes,accelerates recovery,and reduces economic burden.This approach offers a promising reference for improving patient care and rehabilitation efficiency following lung surgery.
文摘Stavudine, a potent anti HIV and AIDS related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcriptase by acting as a false substrate. Modifications made on the hydrogen labile at the 5' position on the sugar is an interesting template for the elaboration of new potent anti HIV and AIDS drugs. The expected advantages of the modified stavudine prodrugs can be multiple: synergistic drug activities, enhancement of stavudine intracellular uptake, increase of stavudine brain delivery, and bypass of the first stavudine phosphorylation step into the cells. Nitric oxide synthase inhibitors of stavudine and nitric oxide donors of stavudine may hold significant promise for the treatment of HIV and AIDS.
文摘Nitric oxide (NO) has been implicated in the promotion of neurodegeneration. However, little is known about the relationship between NO and the self-renewal or differentiation capacity of neural stem cells (NSCs) in neurodegenerative disease. In this study, we investigated the effect of NO on self-renewal of NSCs in an animal model for Niemann-Pick type C (NPC) disease. We found that NO production was significantly increased in NSCs from NPCl-deficient mice (NPCI^-/-), which showed reduced NSC self-renewal. The number of nestin-positive cells and the size of neurospheres were both significantly decreased. The expression of NO synthase (NOS) was increased in neurospheres derived from the brain of NPC1^-/- mice in comparison to wild-type neurospheres. NO-mediated activation of glycogen synthase ki- nase-3β (GSK3β) and caspase-3 was also observed in NSCs from NPC1^-/- mice. The self-renewal ability of NSCs from NPC1^-/- mice was restored by an NOS inhibitor, L-NAME, which resulted in the inhibition of GSK3β and caspase-3. In addition, the differentiation ability of NSCs was partially restored and the number of Fluoro-Jade C-positive degenerating neurons was reduced. These data suggest that overproduction of NO in NPC disease impaired the self-renewal of NSCs. Control of NO production may be key for the treatment of NPC disease.
文摘AIM:To clarify whether the vasoconstrictory response is impaired and to study vascular function in patients with migraine during the headache attack.METHODS:We studied vascular reactivity in the resistance arteries by using the forearm perfusion technique associated with plethysmography.We measuredforearm blood flow by strain-gauge plethysmography during intra-brachial infusion of acetylcholine,sodium nitroprusside or norepinephrine in 11 controls and 13patients with migraine,11 of them(M) in the interval between the migraine attacks and 4 during a headache attack(MH).Written informed consent was obtained from patients and healthy controls,and the study was approved by the Ethics Committee of the University Federico Ⅱ.RESULTS:Compared to healthy control subjects,in patients with migraine studied during the interictal period,the vasodilating effect of acetylcholine,that acts through the stimulation of endothelial cells and the release of nitric oxide,was markedly reduced,but became normal during the headache attack(P<0.05by analysis of variance).The response to nitroprusside,which directly relaxes vascular smooth muscle cells(VSMCs),was depressed in patients with migraine studied during the interictal period,but normal during the headache attack(P<0.005).During norepinephrine infusion,forearm blood flow decreased in control subjects(-40% ± 5%,P<0.001).In contrast,in patients with migraine,either when studied during or free of the headache attack forearm blood flow did not change compared to the baseline value(-3%±13% and-10.4%±15%,P>0.05).CONCLUSION:In migrainers,the impaired relaxation of VSMCs is restored during the headache attack.The vasoconstrictory response is impaired and remains unchanged during the migraine attack.
基金supported by National Natural Science Foundation of China(81502627)the Young Backbone Teachers Assistance Scheme of Henan Province Colleges and Universities(2016GGJS-065)
文摘OBJECTIVE To investigate the regulation of {O^2(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate}(JS-K),anitric oxide donor,on tumor energy metabolism in H22 tumor-bearing mice.METHODS The hepatoma animal model in BALB/c mice was established with H22 cell line.The JS-K group and model group were received JS-K(0.75 and 1.5 mg?kg^(-1)) and saline via tail intravenous once every 3 d for 14 d,received 5 injections,respectively.The positive group was received 5-FU 20 mg·kg^(-1) by intraperitoneal injection once a day for 14 d.On the 15 th day mice were sacrificed.The tumor growth inhibition rate were calculated.The activities of hexokinase(HK),phosphofructo kinase(PFK),pyruvate kinase(PK),succinate dehydrogenase(SDH),adenosine triphosphatase(ATPase),and the levels of lactic acid(LD) and adenosine triphosphate(ATP) in tumor tissues were determined by colorimetric method.RESULTS Compared with model group,the tumor mass of JS-K0.75 and 1.5 mg·kg^(-1) group was significantly reduced(P<0.01),and the tumor growth inhibition rate was 23.9% and 50.3%,respectively.The activity of HK,PFK,PK,SDH and ATPase of tumor tissue in model group was(22.6±3.7,14.4±2.6,12.9±3.2 and 10.5±2.6)U·g^(-1) protein and(0.70±0.10)μmol Pi·mg^(-1) protein per hour,respectively;which in JS-K 1.5 mg?kg^(-1) group was dropped by 42.0%,26.6%,22.7%,23.3% and 21.7%(P<0.01,P<0.05).Compared with the model group,the level of ATP and LD in JS-K group was dropped(P<0.01).CONCLUSION JS-K can inhibit the growth of tumor in H22 tumor-bearing mice and its mechanism may be related to regulating the tumor energy metabolism with inhibition of glycolysis and aerobic oxidation.
基金Supported by Science Fund for Youths(No.81300763)
文摘AIM: To clarify how the endothelial nitric oxide synthase (eNOS, NOS3) make effect on outflow facility through the trabecular meshwork (TM). METHODS: Inhibition of NOS3 gene expression in human TM cells were conducted by three siRNAs. Then the mRNA and protein levels of NOS3 in siRNA-treated and negative control (NC) cells were determined, still were the collagen, type IV, alpha 1 (COL4A1) and fibronectin 1 by real-time PCR and Western blot analysis. In addition, NOS3 concentrations in culture supernatant fluids of TM cells were measured. Cell cycle and cell apoptosis analysis were performed using flow cytometry. RESULTS: The mRNA level of NOS3 was decreased by three different siRNA interference, similar results were obtained not only of the relative levels of NOS3 protein, but also the expression levels of COL4A1 and fibronectin 1. The number of cells in S phase was decreased, while contrary result was obtained in G2 phase. The number of apoptotic cells in siRNA-treated groups were significant increased compared to the NC samples. CONCLUSION: Abnormal NOS3 expression can make effects on the proteins levels of extracellular matrix component (e.g. fibronectin 1 and COL4A1). Reduced NOS3 restrains the TM cell cycle progression at the G2/ M-phase transition and induced cell apoptosis.
文摘R Nitric oxide probably plays an important role in mechanisms determining sexual dimorphism in the development of cardiovascular diseases, including hypertension. Because stress together with gender are significant cardiovascular risk factors, we studied the role nitric oxide in car-diovascular regulation in male and female nor-motensive and hypertensive rats under normal and stress conditions. Experiments were per-formed in mongrel normotensive and hyperten-sive (two kidney, one clip) rats of both sexes, weighing 200-250g. The study of mean arterial pressure and heart rate was carried out: 1) under control condition;2) during nitric oxide blo- ckade by NG-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg, iv) 3) during 60 min immobilization stress and recovery;4) during 60 min immobi-lization stress + L-NAME and recovery. We found that the severity of hypertension in fe-males was lower than in males. We also ob-served that both normotensive and hyperten-sive females demonstrated more favorable pat-tern of cardiovascular responses to stress. At rest, nitric oxide blockade increased the mean arterial pressure and decreased the heart rate more effectively in female normotensive and hypertensive rats than in male groups. During stress, nitric oxide blockade modified the stress- induced cardiovascular responses more sig-nificantly in female normotensive and hyper-tensive rats compared with male groups. Our data show that both normotensive and hyper-tensive females demonstrated the more effec-tive nitric oxide control of cardiovascular activ-ity under normal and especially stress condi-tions than male groups. This male-female dif-ference may be important mechanism respon-sible for greater in females vs. males of cardio-vascular resistance to stress and development of hypertension.
文摘AIM: To assess whether a liver specific nitric oxide (NO) donor (V-PYRRO/NO) would prevent the development of portal hypertension and liver fibrosis in rats with bile duct ligation (BDL). METHODS: Treatment (placebo or V-PYRRO/NO 0.53 μmol/kg per hour) was administered i.v. to rats 2 d before BDL (D-2) and maintained until the day of hemodynamic measurement (D26). Intra-hepatic NO level was estimated by measuring liver cGMP level. Effects of V-PYRRO/NO on liver fibrosis and lipid peroxidation were also assessed. RESULTS: Compared to placebo treatment, V-PYRRO/ NO improved splanchnic hemodynamics in BDL rats: portal pressure was significantly reduced by 27% (P < 0.0001) and collateral circulation development was almost completely blocked (splenorenal shunt blood flow by 74%, P = 0.007). Moreover, V-PYRRO/NO significantly prevented liver fibrosis development in BDL rats (by 30% in hepatic hydroxyproline content and 31% in the area of fibrosis, P < 0.0001 respectively), this effect being probably due to a decrease in lipid peroxidation by 44% in the hepatic malondialdehyde level (P = 0.007). Interestingly, we observed a significant and expected increase in liver cGMP, without any systemic hemodynamic effects (mean arterial pressure, vascular systemic resistance and cardiac output) in both sham- operated and BDL rats treated with V-PYRRO/NO. This result is in accordance with studies on V-PYRRO/NO metabolism showing a specific release of NO in the liver.NO in BDL rats improved liver fibrosis and splanchnic hemodynamics without any noxious systemic hemo- dynamic effects.
文摘Background: The ideal agent for cervical ripening would induce adequate cervical ripening with minimal adverse effects to the mother and the fetus;the most favorable method for cervical ripening is not fully agreed till now;however, vaginal administration of isosorbide mononitrate (IMN) is considered a low-risk method of labor induction for post term. Our study was designed to assess the effect of IMN on cervical ripening and labor induction among 41 weeks pregnant women. Objectives: To assess the efficacy of the nitric oxide donor isosorbide mononitrate on cervical ripening at 41 weeks gestation. Materials and Methods: This study was conducted on 100 pregnant women recruited from the outpatient clinic fulfilling the inclusion criteria. Cases were divided into 2 groups. In first group 40 mg isosorbide mononitrate (IMN) tablet was applied vaginally in posterior fornix, and in second group placebo was applied vaginally in posterior fornix. Following up the cervical status after 24 hours of administration, the patient were asked about new symptoms especially headache, palpitation, dizziness or abdominal pain and the mode of delivery was assessed. Results: There was a significant improvement in the bishop score in the first group rather than the placebo group. No significant difference between the two groups was as regards the mode of delivery. Conclusion: IMN may be used for cervical preparation only before induction of labor in post term cases.
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.