BACKGROUND The frequent occurrence of respiratory diseases in the island reef environment of the navy severely affects the health of personnel and the combat effectiveness of the troops.Current common screening method...BACKGROUND The frequent occurrence of respiratory diseases in the island reef environment of the navy severely affects the health of personnel and the combat effectiveness of the troops.Current common screening methods can only indicate whether there is an infection with pathogenic microorganisms but not the degree of disease progression.Therefore,it is necessary to identify simple-to-operate and cost-effective methods that indicate the degree of disease progression,based on traditional screening methods.AIM To explores correlation between serum concentrations of nicotinamide phosphoribosyltransferase(NAMPT),nicotinamide nucleotide adenylyltransferase 1(NMNAT1),and the risk of upper respiratory infections in the island reef envirsonment.METHODS A total of 600 cases of upper respiratory infections among naval officers and soldiers were included.Types of infection were confirmed through sputum culture combined with multiplex polymerase chain reaction.The serum concentrations of NAMPT and NMNAT1 were measured using ELISA,and infection severity was assessed using the pneumonia severity index(PSI).Statistical analysis was performed using nonparametric tests and Spearman correlation analysis.RESULTS The serum concentrations of NAMPT and NMNAT1 in high-risk group patients with PSI were significantly lower than those in the medium and low-risk groups(P<0.05),and the concentrations increased in a stepwise manner with disease progression.However,within the same risk group,the differences in concentrations of NAMPT and NMNAT1among patients infected with different pathogens were not significant(P>0.05).CONCLUSIONConcentrations of NAMPT and NMNAT1 are closely related to severity of upper respiratory infections,and theircommon regulatory mechanisms provide new directions for development of broad-spectrum anti-infectionstrategies.展开更多
Nicotinamide mononucleotide(NMN),a precursor in nicotinamide adenine dinucleotide(NAD)biosynthesis,has long been recognized for its pivotal role in medicine.Recent investigations have suggested its potential as a plan...Nicotinamide mononucleotide(NMN),a precursor in nicotinamide adenine dinucleotide(NAD)biosynthesis,has long been recognized for its pivotal role in medicine.Recent investigations have suggested its potential as a plant immunity inducer for controlling fungal diseases.However,whether NMN confers plant broad-spectrum resistance against diverse phytopathogens,and its underlying mechanisms remain ambiguous.In this study,we investigate the effect of NMN against multiple phytopathogens in tobacco.Our results demonstrate that tobacco pretreated with NMN exhibits enhanced resistance against Ralstonia solanacearum CQPS-1,Pseudomonas syringae DC3000ΔhopQ1-1,Phytophthora parasitica,and tobacco mosaic virus(TMV).NMN displays effectiveness within the concentration range of 50–600μmol L^(–1),with75μmol L^(–1)NMN exhibiting the most pronounced effect.The impact of NMN pretreatment could persist for up to 10 days.Beyond tobacco,NMN pretreatment enhances disease resistance in tomato and pepper plants against diverse pathogens,underscoring NMN’s capacity to confer broad-spectrum disease resistance in crops.Moreover,RT-qPCR analysis reveals that NMN significantly upregulates the expression of the pattern-triggered immunity(PTI)marker gene NbCYP71D20 and salicylic acid(SA)marker gene NbPR1a.This suggests that NMN enhances plant resistance by inducing both PTI and SA-mediated immunity.Interestingly,the positive impact of NMN on plant disease resistance is not significantly compromised in both NMN adenylyltransferase(NMNAT)-silenced plants and NAD receptor mutant lecrk-I.8,suggesting the existence of NAD-independent signaling pathways for NMN-induced plant immunity.In conclusion,our study establishes that the bioactive molecule NMN imparts broad-spectrum disease resistance in plants,offering a simple,environmental-friendly,and promising strategy for safeguarding crops against diverse phytopathogens.These findings also provide valuable insights for future in-depth studies into the functional mechanisms of NMN.展开更多
Background:Acute-onset neurodegenerative diseases in older patients are rare clinical cases,especially when the degeneration only affects specific regions of the nervous system.Several neurological disorders have been...Background:Acute-onset neurodegenerative diseases in older patients are rare clinical cases,especially when the degeneration only affects specific regions of the nervous system.Several neurological disorders have been described in which the degeneration of brain parenchyma originates from and/or primarily affects the brain stem.Clinical diagnosis in these patients,however,is often complicated due to a poor understanding of these diseases and their underlying mechanisms.Case presentation:In this manuscript we report on a 73-year-old female who had experienced a sudden onset of complex neurological symptoms that progressively worsened over a period of 2 years.Original evaluation had suggested a MRI-negative stroke as underlying pathogenesis.The combination of patient’s medical history,clinical examination and exceptional pattern of brain stem degeneration presenting as“kissing swan sign”in MR imaging was strongly suggestive of acute onset of Alexander’s disease.This leukoencephalopathy is caused by GFAP(glial fibrilary acidic protein)gene mutations and may present with brain stem atrophy and stroke-like onset of symptoms in elderly individuals.However,a pathognomonic GFAP gene mutation could not be identified by Sanger sequencing.Conclusions:After an extended differential diagnosis and exclusion of other diseases,a definite diagnosis of the patient’s condition presently remains elusive.However,whole-exome sequencing performed from patient’s blood revealed 12 potentially disease-causative heterozygous variants,amongst which several have been associated with neurological disorders in vitro and in vivo–in particular the axon degeneration-related NMNAT2 gene.展开更多
Pathological cardiac hypertrophy is a maladaptive response in a variety of organic heart disease(OHD),which is characterized by mitochondrial dysfunction that results from disturbed energy metabolism.SIRT3,a mitochond...Pathological cardiac hypertrophy is a maladaptive response in a variety of organic heart disease(OHD),which is characterized by mitochondrial dysfunction that results from disturbed energy metabolism.SIRT3,a mitochondria-localized sirtuin,regulates global mitochondrial lysine acetylation and preserves mitochondrial function.However,the mechanisms by which SIRT3 regulates cardiac hypertrophy remains to be further elucidated.In this study,we firstly demonstrated that expression of SIRT3 was decreased in AngiotensionⅡ(AngⅡ)-treated cardiomyocytes and in hearts of AngⅡ-induced cardiac hypertrophic mice.In addition,SIRT3 overexpression protected myocytes from hypertrophy,whereas SIRT3 silencing exacerbated AngⅡ-induced cardiomyocyte hypertrophy.In particular,SIRT3-KO mice exhibited significant cardiac hypertrophy.Mechanistically,we identified NMNAT3(nicotinamide mononucleotide adenylyltransferase 3),the rate-limiting enzyme for mitochondrial NAD biosynthesis,as a new target and binding partner of SIRT3.Specifically,SIRT3 physically interacts with and deacetylates NMNAT3,thereby enhancing the enzyme activity of NMNAT3 and contributing to SIRT3-mediated anti-hypertrophic effects.Moreover,NMNAT3 regulates the activity of SIRT3 via synthesis of mitochondria NAD.Taken together,these findings provide mechanistic insights into the negative regulatory role of SIRT3 in cardiac hypertrophy.Sirtuin 3(SIRT3),a mitochondrial deacetylase that may play an important role in regulating cardiac function and a potential target for CHF.展开更多
Although the nicotinamide nucleotides NAD（H） and NADP（H） are essential for various metabolic reactions that play major roles in maintenance of cellular homeostasis, the significance of NAD biosynthesis is not well...Although the nicotinamide nucleotides NAD（H） and NADP（H） are essential for various metabolic reactions that play major roles in maintenance of cellular homeostasis, the significance of NAD biosynthesis is not well under- stood. Here, we investigated the dynamics of pollen nicotinamide nucleotides in response to imbibition, a representative germination cue. Metabolic analysis with capillary electrophoresis electrospray ionization mass spectrometry revealed that excess amount of NAD＊ is accumulated in freshly harvested dry pollen, whereas it dramatically decreased immedi- ately after contact with water, importantly, excess of NAD~ impaired pollen tube growth. Moreover, NAD~ accumulation was retained after pollen was imbibed in the presence of NAD^-consuming reaction inhibitors and pollen germination was greatly retarded. Pollen deficient in the nicotinate/nicotinamide mononucleotide adenyltransferase （NMNAT） gene, encoding a key enzyme in NAD biosynthesis, and a lack of NAD＊ accumulation in the gametophyte, showed precocious pollen tube germination inside the anther Iocule and vigorous tube growth under high-humidity conditions. Hence, the accumulation of excess NAD＊ is not essential for pollen germination, but instead participates in regulating the timing of germination onset. These results indicate that NAD＋ accumulation acts to negatively regulate germination and a decrease in NAD＋ plays an important role in metabolic state transition.展开更多
文摘BACKGROUND The frequent occurrence of respiratory diseases in the island reef environment of the navy severely affects the health of personnel and the combat effectiveness of the troops.Current common screening methods can only indicate whether there is an infection with pathogenic microorganisms but not the degree of disease progression.Therefore,it is necessary to identify simple-to-operate and cost-effective methods that indicate the degree of disease progression,based on traditional screening methods.AIM To explores correlation between serum concentrations of nicotinamide phosphoribosyltransferase(NAMPT),nicotinamide nucleotide adenylyltransferase 1(NMNAT1),and the risk of upper respiratory infections in the island reef envirsonment.METHODS A total of 600 cases of upper respiratory infections among naval officers and soldiers were included.Types of infection were confirmed through sputum culture combined with multiplex polymerase chain reaction.The serum concentrations of NAMPT and NMNAT1 were measured using ELISA,and infection severity was assessed using the pneumonia severity index(PSI).Statistical analysis was performed using nonparametric tests and Spearman correlation analysis.RESULTS The serum concentrations of NAMPT and NMNAT1 in high-risk group patients with PSI were significantly lower than those in the medium and low-risk groups(P<0.05),and the concentrations increased in a stepwise manner with disease progression.However,within the same risk group,the differences in concentrations of NAMPT and NMNAT1among patients infected with different pathogens were not significant(P>0.05).CONCLUSIONConcentrations of NAMPT and NMNAT1 are closely related to severity of upper respiratory infections,and theircommon regulatory mechanisms provide new directions for development of broad-spectrum anti-infectionstrategies.
基金supported by the Technology Innovation Leading Program of Shaanxi,China(2023QYPY2-01)the National Natural Science Foundation of China(32072399,32302296,and 32372483)+1 种基金the Fundamental Research Funds for the Central Universities(GK202201017 and GK202207024)the Program of Fujian Key Laboratory for Monitoring and Integrated Management of Crop Pests,China(MIMCP-202203)。
文摘Nicotinamide mononucleotide(NMN),a precursor in nicotinamide adenine dinucleotide(NAD)biosynthesis,has long been recognized for its pivotal role in medicine.Recent investigations have suggested its potential as a plant immunity inducer for controlling fungal diseases.However,whether NMN confers plant broad-spectrum resistance against diverse phytopathogens,and its underlying mechanisms remain ambiguous.In this study,we investigate the effect of NMN against multiple phytopathogens in tobacco.Our results demonstrate that tobacco pretreated with NMN exhibits enhanced resistance against Ralstonia solanacearum CQPS-1,Pseudomonas syringae DC3000ΔhopQ1-1,Phytophthora parasitica,and tobacco mosaic virus(TMV).NMN displays effectiveness within the concentration range of 50–600μmol L^(–1),with75μmol L^(–1)NMN exhibiting the most pronounced effect.The impact of NMN pretreatment could persist for up to 10 days.Beyond tobacco,NMN pretreatment enhances disease resistance in tomato and pepper plants against diverse pathogens,underscoring NMN’s capacity to confer broad-spectrum disease resistance in crops.Moreover,RT-qPCR analysis reveals that NMN significantly upregulates the expression of the pattern-triggered immunity(PTI)marker gene NbCYP71D20 and salicylic acid(SA)marker gene NbPR1a.This suggests that NMN enhances plant resistance by inducing both PTI and SA-mediated immunity.Interestingly,the positive impact of NMN on plant disease resistance is not significantly compromised in both NMN adenylyltransferase(NMNAT)-silenced plants and NAD receptor mutant lecrk-I.8,suggesting the existence of NAD-independent signaling pathways for NMN-induced plant immunity.In conclusion,our study establishes that the bioactive molecule NMN imparts broad-spectrum disease resistance in plants,offering a simple,environmental-friendly,and promising strategy for safeguarding crops against diverse phytopathogens.These findings also provide valuable insights for future in-depth studies into the functional mechanisms of NMN.
文摘Background:Acute-onset neurodegenerative diseases in older patients are rare clinical cases,especially when the degeneration only affects specific regions of the nervous system.Several neurological disorders have been described in which the degeneration of brain parenchyma originates from and/or primarily affects the brain stem.Clinical diagnosis in these patients,however,is often complicated due to a poor understanding of these diseases and their underlying mechanisms.Case presentation:In this manuscript we report on a 73-year-old female who had experienced a sudden onset of complex neurological symptoms that progressively worsened over a period of 2 years.Original evaluation had suggested a MRI-negative stroke as underlying pathogenesis.The combination of patient’s medical history,clinical examination and exceptional pattern of brain stem degeneration presenting as“kissing swan sign”in MR imaging was strongly suggestive of acute onset of Alexander’s disease.This leukoencephalopathy is caused by GFAP(glial fibrilary acidic protein)gene mutations and may present with brain stem atrophy and stroke-like onset of symptoms in elderly individuals.However,a pathognomonic GFAP gene mutation could not be identified by Sanger sequencing.Conclusions:After an extended differential diagnosis and exclusion of other diseases,a definite diagnosis of the patient’s condition presently remains elusive.However,whole-exome sequencing performed from patient’s blood revealed 12 potentially disease-causative heterozygous variants,amongst which several have been associated with neurological disorders in vitro and in vivo–in particular the axon degeneration-related NMNAT2 gene.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81673433,No.81026548 and No.81273499),Team item of the Natural Science Foundation of Guangdong Province(No.S2011030003190).
文摘Pathological cardiac hypertrophy is a maladaptive response in a variety of organic heart disease(OHD),which is characterized by mitochondrial dysfunction that results from disturbed energy metabolism.SIRT3,a mitochondria-localized sirtuin,regulates global mitochondrial lysine acetylation and preserves mitochondrial function.However,the mechanisms by which SIRT3 regulates cardiac hypertrophy remains to be further elucidated.In this study,we firstly demonstrated that expression of SIRT3 was decreased in AngiotensionⅡ(AngⅡ)-treated cardiomyocytes and in hearts of AngⅡ-induced cardiac hypertrophic mice.In addition,SIRT3 overexpression protected myocytes from hypertrophy,whereas SIRT3 silencing exacerbated AngⅡ-induced cardiomyocyte hypertrophy.In particular,SIRT3-KO mice exhibited significant cardiac hypertrophy.Mechanistically,we identified NMNAT3(nicotinamide mononucleotide adenylyltransferase 3),the rate-limiting enzyme for mitochondrial NAD biosynthesis,as a new target and binding partner of SIRT3.Specifically,SIRT3 physically interacts with and deacetylates NMNAT3,thereby enhancing the enzyme activity of NMNAT3 and contributing to SIRT3-mediated anti-hypertrophic effects.Moreover,NMNAT3 regulates the activity of SIRT3 via synthesis of mitochondria NAD.Taken together,these findings provide mechanistic insights into the negative regulatory role of SIRT3 in cardiac hypertrophy.Sirtuin 3(SIRT3),a mitochondrial deacetylase that may play an important role in regulating cardiac function and a potential target for CHF.
文摘Although the nicotinamide nucleotides NAD（H） and NADP（H） are essential for various metabolic reactions that play major roles in maintenance of cellular homeostasis, the significance of NAD biosynthesis is not well under- stood. Here, we investigated the dynamics of pollen nicotinamide nucleotides in response to imbibition, a representative germination cue. Metabolic analysis with capillary electrophoresis electrospray ionization mass spectrometry revealed that excess amount of NAD＊ is accumulated in freshly harvested dry pollen, whereas it dramatically decreased immedi- ately after contact with water, importantly, excess of NAD~ impaired pollen tube growth. Moreover, NAD~ accumulation was retained after pollen was imbibed in the presence of NAD^-consuming reaction inhibitors and pollen germination was greatly retarded. Pollen deficient in the nicotinate/nicotinamide mononucleotide adenyltransferase （NMNAT） gene, encoding a key enzyme in NAD biosynthesis, and a lack of NAD＊ accumulation in the gametophyte, showed precocious pollen tube germination inside the anther Iocule and vigorous tube growth under high-humidity conditions. Hence, the accumulation of excess NAD＊ is not essential for pollen germination, but instead participates in regulating the timing of germination onset. These results indicate that NAD＋ accumulation acts to negatively regulate germination and a decrease in NAD＋ plays an important role in metabolic state transition.
