β-Cyclodextrin-Based Nitrosoglutathione Improves the Storage Quality of Peach by Regulating the Metabolism of Endogenous Nitric Oxide, Hydrogen Sulfide, and Phenylpropane

Nitrosoglutathione(GSNO)andβ-cyclodextrin(β-CD)exhibit positive roles in regulating fruit quality.However,there are few reports about the effects of GSNO andβ-CD on enhancing storability and boosting nitric oxide(NO),hydrogen sulfide(H2S),and phenylpropane metabolism in fruits during storage.“Xintaihong”peach were treated with 0.5,1.0,1.5mmol L−1 GSNO in 0.5%(w/v)β-CD solution(GSNO/β-CD).The effects of GSNO/β-CD on endogenous NO,H2S,and phenylpropane metabolism were investigated.Treatment with GSNO/β-CD increased the color difference of peach and inhibited the increase of respiratory intensity,weight loss,and relative conductivity.Treatment with 1.0 mmol L−1 GSNO/β-CD increased the nitric oxide synthase(NOS-like)activity and L-arginine content,thereby promoting the accumulation of endogenous NO.By improving the activities of L-cysteine desulfhydrylase(L-CD),O-acetylserine sulfur lyase(OAS-TL),serine acetyltransferase(SAT),GSNO/β-CD increased the content of endogenous H2S in peach.Treatment with GSNO/β-CD increased the activities of phenylalanine ammonia-lyase(PAL),4-coumarate-CoA ligase(4CL),and cinnamic acid-4-hydroxylase(C4H),promoted the increase of total phenols,flavonoids,and lignin in peach.These results indicated that GSNO/β-CD treatment better maintained the quality of peach by improving the metabolism of endogenous NO,H2S,and phenylpropane during storage.

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

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.

Nitric oxide removal from flue gas coupled with the Fe^(Ⅱ)EDTA regeneration by ultraviolet irradiation

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.

Elimination of methicillin‑resistant Staphylococcus aureus biofilms on titanium implants via photothermally‑triggered nitric oxide and immunotherapy for enhanced osseointegration

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.

Carbon Monoxide Modulates Auxin Transport and Nitric Oxide Signaling in Plants under Iron Deficiency Stress

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.

Operation room nursing based on humanized nursing mode combined with nitric oxide on rehabilitation effect after lung surgery

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.

Effects of Nitric Oxide on the Germination of Wheat Seeds and Its Reactive Oxygen Species Metabolisms Under Osmotic Stress

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).

Silicon and Nitric Oxide-Mediated Regulation of Growth Attributes, Metabolites and Antioxidant Defense System of Radish (Raphanus sativus L.) under Arsenic Stress

Arsenic(As)contaminated food chains have emerged as a serious public concern for humans and animals and are known to affect the cultivation of edible crops throughout the world.Therefore,the present study was designed to investigate the individual as well as the combined effects of exogenous silicon(Si)and sodium nitroprusside(SNP),a nitric oxide(NO)donor,on plant growth,metabolites,and antioxidant defense systems of radish(Raphanus sativus L.)plants under three different concentrations of As stress,i.e.,0.3,0.5,and 0.7 mM in a pot experiment.The results showed that As stress reduced the growth parameters of radish plants by increasing the level of oxidative stress markers,i.e.,malondialdehyde and hydrogen peroxide.However,foliar application of Si(2 mM)and pretreatment with SNP(100μM)alone as well as in combination with Si improved the plant growth parameters,i.e.,root length,fresh and dry weight of plants under As stress.Furthermore,As stress also reduced protein,and metabolites contents(flavonoids,phenolic and anthocyanin).Activities of antioxidative enzymes such as catalase(CAT),ascorbate peroxidase(APX),guaiacol peroxidase(POD),and polyphenol oxidase(PPO),as well as the content of non-enzymatic antioxidants(glutathione and ascorbic acid)decreased under As stress.In most of the parameters in radish,As III concentration showed maximum reduction,as compared to As I and II concentrations.However,the individual and combined application of Si and NO significantly alleviated the As-mediated oxidative stress in radish plants by increasing the protein,and metabolites content.Enhancement in the activities of CAT,APX,POD and PPO enzymes were recorded.Contents of glutathione and ascorbic acid were also enhanced in response to co-application of Si and NO under As stress.Results obtained were more pronounced when Si and NO were applied in combination under As stress,as compared to their individual application.In short,the current study highlights that Si and NO synergistically regulate plant growth through lowering the As-mediated oxidative stress by upregulating the metabolites content,activity of antioxidative enzymes and non-enzymatic antioxidants in radish plants.

Effects of Nitric Oxide on the Quality and Pectin Metabolism of Yali Pears During Cold Storage

The effect of fumigation with 10, 20, and 30 μL L-1 nitric oxide （NO） was investigated to study the effects of NO on the quality of Yali pears during cold storage. The ethylene production, composition of cell walls, and cell-wall-modifying enzyme activities were measured on fruits which were fumigated with NO （20 μL L-1）. The results showed that NO not only reduced the peak value of ethylene production rate, the soluble sugar, soluble solid content, maintained higher firmness, starch, and NO content, but also retarded the degradation of covalent soluble pectin, accumulation of ionic soluble pectin and water soluble pectin. Moreover, NO fumigation decreased the activities of polygalacturonase （PG） and b-galactosidase（b-Gal） and delayed the peak of PG activity of fruits. Therefore, it indicated that NO fumigation could delay the softening and ripening of Yali pears.

Effects of 1-MCP on proline,polyamine,and nitric oxide metabolism in postharvest peach fruit under chilling stress

Peach(Prunus persica Batsch‘Yuhualu’)fruit are sensitive to chilling injury(CI).Proline,polyamine(PA),and nitric oxide(NO)are important small regulators of various metabolic pathways under chilling stress that mitigate CI.Ethylene is known to promote senescence and CI,while 1-methylcyclopropene(1-MCP)is an antagonist that inhibits the effects of ethylene.However,how1-MCP and ethylene affect proline,PA,and NO levels under chilling stress remains unclear.To address these questions,1-MCP(1μL·L^(−1))and ethylene(1μL·L^(−1))treatments were applied to peach fruit.Fruit were stored at 4°C for 28 d,then moved to 25°C for 3 d immediately after cold storage.Peach fruit exhibited CI symptoms after 7 d of cold storage with enhanced electrolyte leakage and malondialdehyde contents.The 1-MCP treatment significantly(P<0.05)restrained peach CI,and fruit did not exhibit CI symptoms until 14 d of cold storage.Proline and PAs in peach under chilling stress weremostly synthesized from glutamate and arginine,which were catalyzed by1-pyrroline-5-carboxylate synthetase and arginine decarboxylase,respectively.1-MCPtreated fruit exhibited higher proline and PA contents and enhanced chilling tolerance compared to the control,while ethylene-treated fruit had lower proline and PA contents and reduced chilling tolerance.Ethylene-treated fruit,which exhibited more severe CI symptoms compared to the control,had significantly(P<0.05)lower NO contents and NO synthase activities.However,NOmay not be a direct acting factor in 1-MCPinduced chilling tolerance,as 1-MCP-treated fruit had lower NO contents and NO synthase activities compared to the control.In conclusion,proline and PA clearly played direct and important roles in 1-MCP-induced peach chilling tolerance,while NO may not be actively involved.

Regulation of nitric oxide donor JS-K on tumor energy metabolism in H22 tumor-bearing mice

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.

Rethinking neurodegenerative diseases:neurometabolic concept linking lipid oxidation to diseases in the central nervous system

Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s disease.Given the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these diseases.When considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological features.This innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers worldwide.In this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases.We provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ctors.Additionally,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter disturbances.Finally,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.

Metabolic reprogramming of the inflammatory response in the nervous system:the crossover between inflammation and metabolism

Metabolism is a fundamental process by which biochemicals are broken down to produce energy(catabolism) or used to build macromolecules(anabolism). Metabolism has received renewed attention as a mechanism that generates molecules that modulate multiple cellular responses. This was first identified in cancer cells as the Warburg effect, but it is also present in immunocompetent cells. Studies have revealed a bidirectional influence of cellular metabolism and immune cell function, highlighting the significance of metabolic reprogramming in immune cell activation and effector functions. Metabolic processes such as glycolysis, oxidative phosphorylation, and fatty acid oxidation have been shown to undergo dynamic changes during immune cell response, facilitating the energetic and biosynthetic demands. This review aims to provide a better understanding of the metabolic reprogramming that occurs in different immune cells upon activation, with a special focus on central nervous system disorders. Understanding the metabolic changes of the immune response not only provides insights into the fundamental mechanisms that regulate immune cell function but also opens new approaches for therapeutic strategies aimed at manipulating the immune system.

Targeting the nitric oxide/cGMP signaling pathway to treat chronic pain

Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain, including neuropathic pain, bone cancer pain, inflammatory pain, and morphine tolerance. The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase, which leads to subsequent production of cGMP. cGMP then activates cGMP-dependent protein kinase(PKG), resulting in the activation of multiple targets such as the opening of ATP-sensitive K+ channels. The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules, as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain. In dorsal root ganglion neurons, natriuretic peptide binds to particulate guanylyl cyclase, generating and further activating the cGMP/PKG pathway, and it also contributes to the development of chronic pain. Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models. Notably the NO/cGMP signaling pathway induces expression of downstream effectors, exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain. These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain, and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy.

Neuronal nitric oxide synthase/reactive oxygen species pathway is involved in apoptosis and pyroptosis in epilepsy

Dysfunction of neuronal nitric oxide synthase contributes to neurotoxicity,which triggers cell death in various neuropathological diseases,including epilepsy.Studies have shown that inhibition of neuronal nitric oxide synthase activity increases the epilepsy threshold,that is,has an anticonvulsant effect.However,the exact role and potential mechanism of neuronal nitric oxide synthase in seizures are still unclear.In this study,we performed RNA sequencing,functional enrichment analysis,and weighted gene coexpression network analysis of the hippocampus of tremor rats,a rat model of genetic epilepsy.We found damaged hippocampal mitochondria and abnormal succinate dehydrogenase level and Na+-K+-ATPase activity.In addition,we used a pilocarpine-induced N2a cell model to mimic epileptic injury.After application of neuronal nitric oxide synthase inhibitor 7-nitroindazole,changes in malondialdehyde,lactate dehydrogenase and superoxide dismutase,which are associated with oxidative stress,were reversed,and the increase in reactive oxygen species level was reversed by 7-nitroindazole or reactive oxygen species inhibitor N-acetylcysteine.Application of 7-nitroindazole or N-acetylcysteine downregulated the expression of caspase-3 and cytochrome c and reversed the apoptosis of epileptic cells.Furthermore,7-nitroindazole or N-acetylcysteine downregulated the abnormally high expression of NLRP3,gasdermin-D,interleukin-1βand interleukin-18.This indicated that 7-nitroindazole and N-acetylcysteine each reversed epileptic cell death.Taken together,our findings suggest that the neuronal nitric oxide synthase/reactive oxygen species pathway is involved in pyroptosis of epileptic cells,and inhibiting neuronal nitric oxide synthase activity or its induced oxidative stress may play a neuroprotective role in epilepsy.

Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway

Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of angiogenesis during the regeneration process,we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells,thereby promoting microvascular regeneration in aged mice after spinal cord injury.In this study,we established young and aged mouse models of contusive spinal cord injury using a modified Allen method.We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord.Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro.Furthermore,intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord,thereby improving neurological function.The role of metformin was reversed by compound C,an adenosine monophosphate-activated protein kinase inhibitor,both in vivo and in vitro,suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury.These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway,thereby improving the neurological function of aged mice after spinal cord injury.

Polyphenols and pectin enriched golden kiwifruit (Actinidia chinensis) alleviates high fructose-induced glucolipid disorders and hepatic oxidative damage in rats:in association with improvement of fatty acids metabolism

This study aimed to investigate the protective effects of fleshes from two Actinidia chinensis(ACF), pericarps from two A. chinensis(ACP), and fleshes with pericarps from two A. chinensis(ACFP)on high fructose(HF)-instigated dyslipidemia, hepatic steatosis, oxidative stress, insulin resistance, and fatty acid metabolism disorders in rats. In general, the above abnormalities were improved after 10 weeks intervention of ACF, ACP, and ACFP. Especially, ACFP considerably ameliorated HF-induced abnormal changes in body weight gain, serum TC, TG, LDL-C and HDL-C levels, as well as serum and hepatic SFAs, MUFAs and PUFAs contents. ACFP also alleviated HF-induced hyperglycemia and hyperinsulinemia, stabilized HF-caused increase in hepatic MDA and serum ALT, AST levels, and restored HF-declined hepatic T-SOD and GSH-Px activities. Besides, histopathology of the liver further endorsed the protective effects of ACFP on hepatocellular injury. Moreover, ACFP increased HF-dropped acetic, propionic and butyric acid levels. Overall, ACFP employs more efficacious protective effects against HF-induced metabolic disorders and liver damage than ACF and ACP. This study delivers a scientific foundation for developing kiwifruit(counting peel)-based dietary supplements for those with glucolipid-metabolic disorders and liver damage.

Zataria multiflora and its constituent,carvacrol,counteract sepsis-induced aortic and cardiac toxicity in rat:Involvement of nitric oxide and oxidative stress

Background:Zataria multiflora and carvacrol showed various pharmacological prop-erties including anti-inflammatory and anti-oxidant effects.However,up to now no studies have explored its potential benefits in ameliorating sepsis-induced aortic and cardiac injury.Thus,this study aimed to investigate the effects of Z.multiflora and carvacrol on nitric oxide(NO)and oxidative stress indicators in lipopolysaccharide(LPS)-induced aortic and cardiac injury.Methods:Adult male Wistar rats were assigned to:Control,lipopolysaccharide(LPS)(1 mg/kg,intraperitoneal(i.p.)),and Z.multiflora hydro-ethanolic extract(ZME,50–200 mg/kg,oral)-and carvacrol(25–100 mg/kg,oral)-treated groups.LPS was in-jected daily for 14 days.Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration.At the end of the study,the levels of malondialdehyde(MDA),NO,thiols,and antioxidant enzymes were evaluated.Results:Our findings showed a significant reduction in the levels of superoxide dis-mutase(SOD),catalase(CAT),and thiols in the LPS group,which were restored by ZME and carvacrol.Furthermore,ZME and carvacrol decreased MDA and NO in car-diac and aortic tissues of LPS-injected rats.Conclusions:The results suggest protective effects of ZME and carvacrol on LPS-induced cardiovascular injury via improved redox hemostasis and attenuated NO pro-duction.However,additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.

Cell-Based Biological Markers for Blood-Enriching Chinese Herbs: Erythropoietin Production in HepG2 Cells and Nitric Oxide Release in Human Umbilical Vein Endothelial Cells (HUVECs)

Chinese tonifying herbs, which are classified into four functional categories (namely, Yang, Qi, Yin, Blood) are commonly used for restoring normal body function and the prevention of diseases. To explore cell-based biological markers for Blood-enriching Chinese herbs, we investigate the effect of 11 commonly used Blood-enriching herbs on erythropoietin (EPO) production in HepG2 cells. Herbs for nourishing Yin were tested for determining the specificity of Blood-enriching herbs in inducing EPO production. In addition, the effects of Blood-enriching herbs on nitric oxide (NO) production in both HepG2 cells and human umbilical vein endothelial cells (HUVECs) were also investigated. The results indicated that methanolic extracts of Blood-enriching herbs (but not Yin-nourishing herbs) showed characteristic pharmacological activity in inducing EPO production in HepG2 cells and NO release in HUVECs. The experimental findings, therefore, support the use of cell-based EPO production and NO release as biological markers for Blood-enriching Chinese tonifying herbs.

Impact of endothelial nitric oxide synthase activation on accelerated liver regeneration in a rat ALPPS model

BACKGROUND Although the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)induces more rapid liver regeneration than portal vein embolization,the mechanism remains unclear.AIM To assess the influence of inflammatory cytokines and endothelial nitric oxide synthase(eNOS)activation on liver regeneration in ALPPS.METHODS The future liver remnant/body weight(FLR/BW)ratio,hepatocyte proliferation,inflammatory cytokine expression,and activation of the Akt-eNOS pathway were evaluated in rat ALPPS and portal vein ligation(PVL)models.Hepatocyte proliferation was assessed based on Ki-67 expression,which was confirmed using immunohistochemistry.The serum concentrations of inflammatory cytokines were measured using enzyme linked immune-solvent assays.The Akt-eNOS pathway was assessed using western blotting.To explore the role of inflammatory cytokines and NO,Kupffer cell inhibitor gadolinium chloride(GdCl3),NOS inhibitor N-nitro-arginine methyl ester(L-NAME),and NO enhancer molsidomine were administered intraperitoneally.RESULTS The ALPPS group showed significant FLR regeneration(FLR/BW:1.60%±0.08%,P<0.05)compared with that observed in the PVL group(1.33%±0.11%)48 h after surgery.In the ALPPS group,serum interleukin-6 expression was suppressed using GdCl3 to the same extent as that in the PVL group.However,the FLR/BW ratio and Ki-67 labeling index were significantly higher in the ALPPS group administered GdCl3(1.72%±0.19%,P<0.05;22.25%±1.30%,P<0.05)than in the PVL group(1.33%±0.11%and 12.78%±1.55%,respectively).Phospho-Akt Ser473 and phospho-eNOS Ser1177 levels were enhanced in the ALPPS group compared with those in the PVL group.There was no difference between the ALPPS group treated with L-NAME and the PVL group in the FLR/BW ratio and Ki-67 labeling index.In the PVL group treated with molsidomine,the FLR/BW ratio and Ki-67 labeling index increased to the same level as in the ALPPS group.CONCLUSION Early induction of inflammatory cytokines may not be pivotal for accelerated FLR regeneration after ALPPS,whereas Akt-eNOS pathway activation may contribute to accelerated regeneration of the FLR.