The purines constitute a family of inter-related compounds that serve a broad range of important intracellular and extracellular biological functions.In particular,adenosine triphosphate(ATP)and its metabolite and pre...The purines constitute a family of inter-related compounds that serve a broad range of important intracellular and extracellular biological functions.In particular,adenosine triphosphate(ATP)and its metabolite and precursor,adenosine,regulate a wide variety of cellular and systems-level physiological processes extending from ATP acting as the cellular energy currency,to the adenosine arising from the depletion of cellular ATP and responding to reduce energy demand and hence to preserve ATP during times of metabolic stress.This inter-relationship provides opportunities for both the diagnosis of energy depletion during conditions such as stroke,and the replenishment of ATP after such events.In this review we address these opportunities and the broad potential of purines as diagnostics and restorative agents.展开更多
Gout is one of the most common forms of inflammatory arthritis, affecting over 8 million adults in the US. Individuals with gout are advised to avoid the habitual intake of purine-rich foods such as meats, seafood, pu...Gout is one of the most common forms of inflammatory arthritis, affecting over 8 million adults in the US. Individuals with gout are advised to avoid the habitual intake of purine-rich foods such as meats, seafood, purine-rich vegetables, and animal protein. An increased risk of developing or having subsequent attacks of gout is particularly associated with the consumption of seafood. However, clinical studies have shown that certain seafood and fish oil supplements that contain large amounts of omega-3 fatty acids provide important cardiovascular benefits. Individuals who might benefit from omega-3 fatty acid supplementation may therefore avoid fish oil products because they contain purines. Currently, there are no distinct high-performance liquid chromatography (HPLC) methods available in the literature that are validated as per the International Conference on Harmonisation (ICH) guidelines for the analysis of omega-3 fatty acid oils or fish oil containing products for purine content. A robust, fast, and efficient reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the specific analysis of the naturally occurring purines guanine, purine, theobromine, and adenine. These purines are often found in fish oil and seafood. The analytical method reported herein quantifies all four purines in fish oil in about 20 minutes.展开更多
C8-Alkyl-substituted purine analogues were synthesized through direct alkylation of 8-H purine with tetrahydrofuran in the presence of Co catalyst in one step. The reactions gave a series of novel C8-oxygen heterocycl...C8-Alkyl-substituted purine analogues were synthesized through direct alkylation of 8-H purine with tetrahydrofuran in the presence of Co catalyst in one step. The reactions gave a series of novel C8-oxygen heterocyclic alkyl purine compounds in good yields under mild reaction conditions by the readily available alkylating reagents, providing a complementary route to the classical coupling reactions for the synthesis of C8-alkyl-substituted purine analogues.展开更多
An efficient procedure for N-alkylation of pyrimidines and purines in the presence of tetra-n-butylammonium hydroxide(TBAH)is described.The method is very practical and the alkylation can occur at room temperature and...An efficient procedure for N-alkylation of pyrimidines and purines in the presence of tetra-n-butylammonium hydroxide(TBAH)is described.The method is very practical and the alkylation can occur at room temperature and the yields of the N-alkyl pyrimidines and purines were found to be excellent.展开更多
The photocatalyzed synthesis of 9-arylpurines has been developed using 9H-purines and non-activated arenes.This method is highly atom economical using an acridinium photocatalyst induced by visible light under air atm...The photocatalyzed synthesis of 9-arylpurines has been developed using 9H-purines and non-activated arenes.This method is highly atom economical using an acridinium photocatalyst induced by visible light under air atmosphere at room temperature.It employs no metal or external oxidant for the synthesis of9-arylpurine derivatives.展开更多
The aim of this study was to determine the time course of changes in extracellular fluid (ECF) concentrations of purines, amino acids, monoamines, and their metabolites in the striatum of rats during ischemia and repe...The aim of this study was to determine the time course of changes in extracellular fluid (ECF) concentrations of purines, amino acids, monoamines, and their metabolites in the striatum of rats during ischemia and reperfusion, using intracerebral microdialysis as the sampling technique. In rats subjected to 20 min forebrain ischemia by four-vessel occlusion, the concentrations of adenosine (Ade), inosine (Ino) and hypoxanthine (Hyp) were found to rise markedly. These changes were accompanied by dramatically elevated levels of aspartate (Asp), glutamate (Glu), taurine (Tau), γ-aminobutyric acid (GABA), dopamine (DA) and norepinephrine (NE), all of which gradually returned to baseline following reperfusion. Concomitantly, the levels of metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) . homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA) and xanthine (Xan) decreased during ischemia and gradually recovered 60～ 90 min after reperfusion. It was concluded that during global brain ischemia, the ECF is flooded with both potentially harmful (e. g. Asp, Glu, DA) and protective (e. g. Tau, GABA, Ade) agents.展开更多
As a vital microorganism during Huangjiu fermentation,fungi have not been thoroughly evaluated for their potential rela-tionship with total purine levels in Huangjiu,which is a major contributing factor to hyperuricem...As a vital microorganism during Huangjiu fermentation,fungi have not been thoroughly evaluated for their potential rela-tionship with total purine levels in Huangjiu,which is a major contributing factor to hyperuricemia(HUA)and gout.In this study,we revealed the correlation between the succession of fungal communities and total purine content during Huangjiu fermentation.Our results demonstrated a continuous increase in total purine content during fermentation,rising from 13.08 to 72.12 mg/L.We observed significant dynamic changes in fungal community composition and diversity throughout the fermentation process,with the highest fungal species richness occurring on the third day.At the phylum level,Ascomycota dominated throughout fermentation(92.5-97.4%).At the genus level,the predominant taxa were Aspergillus(42.5-73.5%),Saccharomyces(0.0-41.1%),and Paecilomyces(0.0-16.9%),with Aspergillus dominating during the initial phase(0-3 days)and Saccharomyces becoming predominant in later stages(6-18 days).Correlation analysis revealed that Saccharomyces cerevisiae showed a strong positive correlation with total purine levels(r=0.73),while Aspergillus intermedius(r=−0.79)and Aspergillus flavus(r=−0.70)exhibited significant negative correlations.Furthermore,we identified that predominant fungal genera participate in purine metabolism.This study enhances our scientific understanding of purine formation mechanisms in Huangjiu and provides a foundation for developing targeted strategies to regulate purine content in future industrial production.展开更多
Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabo...Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabolism,in the aggressiveness and metastatic behavior of BC.Methods:A comprehensive analysis was performed using in silico transcriptomic data(n=2509 patients),immunohistochemical profiling of BC tissues(n=103),and validation through western blotting in multiple BC cell lines.Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource(TIMER),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and the cBioPortal for cancer genomics(cBioPortal)platforms.Correlations between PNP and key epithelial–mesenchymal transition(EMT)markers,molecular subtypes,tumor grades,and stages were examined.Results:PNP was significantly overexpressed in human epidermal growth factor receptor 2(HER-2)-positive and triple-negative BCs compared to luminal subtypes.High PNP levels were strongly associated with advanced BC stages,high-grade tumors,EMT phenotypes,and poor overall survival.Notably,HER-2 inhibition suppressed PNP expression,while PNP gene silencing induced HER-2 upregulation,revealing a reciprocal regulatory loop.Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.Conclusion:Collectively,PNP emerges as a promising biomarker of BC aggressiveness and progression.Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target.Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.展开更多
Objective: To quantify the purine concentrations of the acupoints along the pericardium and nonpericardium meridians under healthy and myocardial ischemia conditions to investigate the relationship between acupoint pu...Objective: To quantify the purine concentrations of the acupoints along the pericardium and nonpericardium meridians under healthy and myocardial ischemia conditions to investigate the relationship between acupoint purine change and body functional status in rats.Methods: A total of 70 rats underwent an operation for myocardial ischemia,while 40 of them survived.They were randomly assigned to the following 5 subgroups:Neiguan(PC 6),Quze(PC 3),Tianquan(PC 2),Quchi(LI 11),and Jianyu(LI 15).Simultaneously,another40 healthy rats were also randomized into the same 5 subgroups as the control group.The tissue ?uids at the acupoints were collected by microdialysis for 30 min.Subsequently,the concentration of adenosine triphosphate(ATP),adenosine diphosphate(ADP),adenosine monophosphate(AMP),and adenosine(ADO) were quanti?ed using the high-performance liquid chromatography method.Results: Compared with the healthy group,the ADO at PC 6(P=0.012),PC 3(P=0.038),PC 2(P=0.024),and LI 15(P=0.042) obviously increased in the model group,while no signi?cant difference was observed at LI 11(P=0.201).However,ATP,ADP,and AMP manifested no significant changes in these areas,except for ATP at LI 15(P=0.036).Conclusions: Myocardial ischemia could induce an increase in ADO at acupoints of the upper arm and shoulder area,suggesting that the body functional status could affect the responsiveness of acupoints.The status of these acupoints could be pathogenically activated by disease,and distribution following some speci?c courses.展开更多
Globally,hyperuricemia is a growing health,social,and economic problem which could cause gout,chronic kidney diseases and other diseases.There are increasing evidences that a sensible diet makes sense to reduce the ri...Globally,hyperuricemia is a growing health,social,and economic problem which could cause gout,chronic kidney diseases and other diseases.There are increasing evidences that a sensible diet makes sense to reduce the risk of hyperuricemia.This review aims to explore the metabolic mechanism of dietary factors and effects of dietary types associated with hyperuricemia.Recommendations for dietary modification to prevent hyperuricemia are as following:decreasing intake of animal organs,seafood,sugar-sweetened,and alcohol beverages is essential;choosing water or unsweetened tea and coffee instead of sweetened beverages is beneficial;and increasing intake of vegetables,reduced-fat dairy products,foods containing fiber,micronutrients and unsaturated fatty acids is helpful.In addition,consumption of fruits and legumes in moderation is advantageous,and low-fructose of fruits and low-purine of non-soy beans are recommended.Moreover,personalized diet needs to be emphasized for hyperuricemic patients accompanied with diverse metabolic diseases.展开更多
Probiotics have been demonstrated to be effective and safe for hyperuricemia(HUA)and gout treatment.Hence,identifying microbes with high uric acid-or purine-metabolizing ability is highly important.Due to the high loa...Probiotics have been demonstrated to be effective and safe for hyperuricemia(HUA)and gout treatment.Hence,identifying microbes with high uric acid-or purine-metabolizing ability is highly important.Due to the high load of uric acid in chicken feces,we hypothesized that the chicken gut would be an excellent source for new uric acid or purine-metabolizing microbes.In this study,we examined chicken gut contents to isolate an Enterococcus faecalis strain(designated CML390)that displayed high uric acid-degrading ability.In vitro experiments indicated that E.faecalis CML390 could effectively metabolize uric acid under both aerobic and anaerobic conditions,and the richer the nutrients,the higher the rate of uric acid degradation.By integrating genomics,transcriptomics,and metabolomics analyses,we revealed two pathways involved in aerobic and anaerobic uric acid degradation,respectively,in this isolate.E.faecalis CML390 relies on oxygen to metabolize uric acid into substances such as allantoin under aerobic conditions,while it also harbors a conserved uric acid-inducible gene cluster for anaerobic uric acid metabolism.An in vivo experiment showed that gavage with live E.faecalis CML390 in a mouse model of HUA(established using a combination of uric acid and potassium oxonate)significantly reduced serum uric acid levels and alleviated HUA.Our findings contribute to the exploration of the pathways and mechanisms of uric acid metabolism in intestinal microorganisms and provide a candidate probiotic for the treatment of HUA and gout.展开更多
Plant height is an important trait that affects the crop yield and overall productivity.The Green Revolution,which began in the 1960s,brought about a remarkable surge in grain production,largely credited to the introd...Plant height is an important trait that affects the crop yield and overall productivity.The Green Revolution,which began in the 1960s,brought about a remarkable surge in grain production,largely credited to the introduction of new wheat(Triticum aestivum)and rice(Oryza sativa)varieties,specifically the dwarf variants.Short plants offer several advantages,including denser planting,resistance to lodging,and easier application of fertilizers or fungicides(Stokstad,2023).展开更多
Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels....Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.展开更多
Injuries to the spinal cord result in permanent disabilities that limit daily life activities.The main reasons for these poor outcomes are the limited regenerative capacity of central neurons and the inhibitory milieu...Injuries to the spinal cord result in permanent disabilities that limit daily life activities.The main reasons for these poor outcomes are the limited regenerative capacity of central neurons and the inhibitory milieu that is established upon traumatic injuries.Despite decades of research,there is still no efficient treatment for spinal cord injury.Many strategies are tested in preclinical studies that focus on ameliorating the functional outcomes after spinal cord injury.Among these,molecular compounds are currently being used for neurological recovery,with promising results.These molecules target the axon collapsed growth cone,the inhibitory microenvironment,the survival of neurons and glial cells,and the re-establishment of lost connections.In this review we focused on molecules that are being used,either in preclinical or clinical studies,to treat spinal cord injuries,such as drugs,growth and neurotrophic factors,enzymes,and purines.The mechanisms of action of these molecules are discussed,considering traumatic spinal cord injury in rodents and humans.展开更多
The separation of a group of 17 purine and its derivatives by capillary zone electrophoresis is presented. A systematic approach was used to study the effect of pH, buffer type, organic modifiers, applied potential, s...The separation of a group of 17 purine and its derivatives by capillary zone electrophoresis is presented. A systematic approach was used to study the effect of pH, buffer type, organic modifiers, applied potential, sodium dodecyl sulfate (SDS) and cyclodextrins on the separation of these purine derivatives. An ideal condition was found for their separation, which was 30 mmol/L sodium borate buffer (pH 9–9.5), 10%(V/V) methanol buffer modifier and 20 kV. Under this condition, the 17 purine derivatives were baseline separated and the linear correlation coefficient for adenine, uric acid and 2-thioxanthine was 0. 99 over two orders of magnitude. The variation of peak areas was less than 4. 6%(n=5) and that of migration times was in the range of 0%–3%, while the samples were injected hydrodynamically at a height of 15 cm and an injection time of 8–10 s. In addition, alcohol, 1-propanol, 1-butanol and acetonitrile were also effective additives in the separation. However, SDS and various β-cyclodextrin (β-CDs) were found to do no good to their separation.展开更多
The chemical synthesis of Guanine arabinoside （ara-G） is extremely complex, time-consuming, and seriously polluted. A two-step enzymatic synthesis process was developed to acquire ara-G easily. 2,6-Diaminopurine ara...The chemical synthesis of Guanine arabinoside （ara-G） is extremely complex, time-consuming, and seriously polluted. A two-step enzymatic synthesis process was developed to acquire ara-G easily. 2,6-Diaminopurine arabinoside （ara-DA） was first synthesized with purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase produced by Enterobacter aerogenes DGW-07. The conversion yield of ara-DA could reach above 90% when the reaction liquid contained 30 mmol·L^-1 uracil arabinoside as arabinose donor, 10 mmol·L^- 1 2,6-diaminopurine as arabinose acceptor in pH 7.0 20 mmol·L^-1 phosphate buffer, and reacted at 60℃ for 48h. Then, ara-DA was effectively transformed into ara-G with adenylate deaminase produced by Aspergillus oryzae DAW-01. The total process had no complex separation and purification.展开更多
Xanthine dehydrogenase, a member of the molybdenum enzyme family, participates in purine metabolism and catalyzes the generation of ureides from xanthine and hypoxanthine. However, the mechanisms by which xanthine deh...Xanthine dehydrogenase, a member of the molybdenum enzyme family, participates in purine metabolism and catalyzes the generation of ureides from xanthine and hypoxanthine. However, the mechanisms by which xanthine dehydrogenase affects rice growth and development are poorly understood. In the present study, we identified a mutant with early leaf senescence and reduced tillering that we named early senescence and less-tillering 1(esl1). Map-based cloning revealed that ESL1 encodes a xanthine dehydrogenase, and it was expressed in all tissues. Chlorophyll content was reduced and chloroplast maldevelopment was severe in the esl1 mutant. Mutation of ESL1 led to decreases in allantoin, allantoate, and ABA contents. Further analysis revealed that the accumulation of reactive oxygen species in esl1 resulted in decreased photosynthesis and impaired chloroplast development, along with increased sensitivity to abscisic acid and abiotic stresses. Ttranscriptome analysis showed that the ESL1 mutation altered the expression of genes involved in the photosynthesis process and reactive oxygen species metabolism.Our results suggest that ESL1 is involved in purine metabolism and the induction of leaf senescence.These findings reveal novel molecular mechanisms of ESL1 gene-mediated plant growth and leaf senescence.展开更多
Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabo...Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabolism is an essential response to oxidative stress, and an imbalance between purine salvage and de novo biosynthesis pathways can generate damaging reactive oxygen species(ROS). Here, we examined the evolution of 117 purine metabolism-related genes to explore the accompanying molecular mechanisms of enhanced purine metabolism in mammals under high oxidative stress. We found that positively selected genes,convergent changes, and nonparallel amino acid substitutions are possibly associated with adaptation to oxidative stress in mammals. In particular, the evolution of convergent genes with c AMP and c GMP regulation roles may protect mammals from oxidative damage. Additionally, 32 genes were identified as under positive selection in cetaceans, including key purine salvage enzymes(i.e., HPRT1), suggesting improved re-utilization of non-recyclable purines avoid hypoxanthine accumulation and reduce oxidative stress. Most intriguingly, we found that six unique substitutions in cetacean xanthine dehydrogenase(XDH), an enzyme that regulates the generation of the ROS precursor xanthine oxidase(XO) during ischemic/hypoxic conditions, show enhanced enzyme activity and thermal stability and diminished XO conversion activity. These functional adaptations are likely beneficial for cetaceans by reducing radical oxygen species production during diving. In summary, our findings offer insights into the molecular and functional evolution of purine metabolism genes in mammalian oxidative stress adaptations.展开更多
FT Ⅰ (AAAAGGGGAAGCAGAG), a poly purine ele-ment within the myloid-lineage specific enhancer (En 1) of the mouse myeloperoxidase gene [1, 2] has been fur-ther characterised. 1, FT Ⅰ functions as a myeloid-lineage spe...FT Ⅰ (AAAAGGGGAAGCAGAG), a poly purine ele-ment within the myloid-lineage specific enhancer (En 1) of the mouse myeloperoxidase gene [1, 2] has been fur-ther characterised. 1, FT Ⅰ functions as a myeloid-lineage specific transcription regulatory element; 2, WEHI 3BD+ cells have higher binding activity to FT Ⅰ and express the proteins which could form the unique DNA-protein com-plex(es) of FT Ⅰ;. 3, The essential sequence for the specific DNA-protein interactions of FT Ⅰ is AAAAGGGGAAGC; 4, South-western analysis in conjunction with the compe-tition assay of the proteins binding to FT Ⅰ, has revealed a 28 kd protein in WEHI 3BD+ cells that displays the properties of the putative transcription factor which acts through FT Ⅰ. These new findings have demonstrated both the functional myeloid-lineage specificity and the novelty of FT Ⅰ.展开更多
AIM To investigate the distribution and function of interstitialcells of Cajal(ICCs) and platelet-derived growth factor receptor-α positive(PDGFRα+) cells in the proximal and distal colon.METHODS The comparison of c...AIM To investigate the distribution and function of interstitialcells of Cajal(ICCs) and platelet-derived growth factor receptor-α positive(PDGFRα+) cells in the proximal and distal colon.METHODS The comparison of colonic transit in the proximal and distal ends was performed by colonic migrating motor complexes(CMMCs). The tension of the colonic smooth muscle was examined by smooth muscle spontaneous contractile experiments with both ends of the smooth muscle strip tied with a silk thread. Intracellular recordings were used to assess electrical field stimulation(EFS)-induced inhibitory junction potentials(IJP) on the colonic smooth muscle. Western blot analysis was used to examine the expression levels of ICCs and PDGFRα in the colonic smooth muscle.RESULTS Treatment with NG-nitro-L-arginine methyl ester hydrochloride(L-NAME) significantly increased the CMMC frequency and spontaneous contractions, especially in the proximal colon, while treatment with MRS2500 increased only distal CMMC activity and smooth muscle contractions. Both CMMCs and spontaneous contractions were markedly inhibited by NPPB, especially in the proximal colon. Accordingly, CyPPA sharply inhibited the distal contraction of both CMMCs and spontaneous contractions. Additionally, the amplitude of stimulationinduced nitric oxide(NO)/ICC-dependent slow IJPs(sIJPs) by intracellular recordings from the smooth muscles in the proximal colon was larger than that in the distal colon, while the amplitude of electric field stimulationinduced purinergic/PDGFRα-dependent fast IJPs(fIJPs) in the distal colon was larger than that in the proximal colon. Consistently, protein expression levels of c-Kit and anoctamin-1(ANO1) in the proximal colon were much higher, while protein expression levels of PDGFRα and small conductance calcium-activated potassium channel 3(SK3) in the distal colon were much higher.CONCLUSION The ICCs are mainly distributed in the proximal colon and there are more PDGFRα+ cells are in the distal colon, which generates a pressure gradient between the two ends of the colon to propel the feces to the anus.展开更多
文摘The purines constitute a family of inter-related compounds that serve a broad range of important intracellular and extracellular biological functions.In particular,adenosine triphosphate(ATP)and its metabolite and precursor,adenosine,regulate a wide variety of cellular and systems-level physiological processes extending from ATP acting as the cellular energy currency,to the adenosine arising from the depletion of cellular ATP and responding to reduce energy demand and hence to preserve ATP during times of metabolic stress.This inter-relationship provides opportunities for both the diagnosis of energy depletion during conditions such as stroke,and the replenishment of ATP after such events.In this review we address these opportunities and the broad potential of purines as diagnostics and restorative agents.
文摘Gout is one of the most common forms of inflammatory arthritis, affecting over 8 million adults in the US. Individuals with gout are advised to avoid the habitual intake of purine-rich foods such as meats, seafood, purine-rich vegetables, and animal protein. An increased risk of developing or having subsequent attacks of gout is particularly associated with the consumption of seafood. However, clinical studies have shown that certain seafood and fish oil supplements that contain large amounts of omega-3 fatty acids provide important cardiovascular benefits. Individuals who might benefit from omega-3 fatty acid supplementation may therefore avoid fish oil products because they contain purines. Currently, there are no distinct high-performance liquid chromatography (HPLC) methods available in the literature that are validated as per the International Conference on Harmonisation (ICH) guidelines for the analysis of omega-3 fatty acid oils or fish oil containing products for purine content. A robust, fast, and efficient reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the specific analysis of the naturally occurring purines guanine, purine, theobromine, and adenine. These purines are often found in fish oil and seafood. The analytical method reported herein quantifies all four purines in fish oil in about 20 minutes.
基金the National Natural Science Foundation of China (No. 21202039)the Program for Science & Technology Innovation Talents in Universities of Henan Province (No. 13HASTIT013)the Foundation for University Young Key Teacher by Henan Province of China (No. 2011GGJS132)
文摘C8-Alkyl-substituted purine analogues were synthesized through direct alkylation of 8-H purine with tetrahydrofuran in the presence of Co catalyst in one step. The reactions gave a series of novel C8-oxygen heterocyclic alkyl purine compounds in good yields under mild reaction conditions by the readily available alkylating reagents, providing a complementary route to the classical coupling reactions for the synthesis of C8-alkyl-substituted purine analogues.
基金Supported by the National Natural Science Foundation of China(No.20172007)the"985"Programs,Ministry of Educa-tion of China
文摘An efficient procedure for N-alkylation of pyrimidines and purines in the presence of tetra-n-butylammonium hydroxide(TBAH)is described.The method is very practical and the alkylation can occur at room temperature and the yields of the N-alkyl pyrimidines and purines were found to be excellent.
基金supported by Basic and Applied Basic Research Foundation of Guangdong Province in China(No.2021A1515012349)。
文摘The photocatalyzed synthesis of 9-arylpurines has been developed using 9H-purines and non-activated arenes.This method is highly atom economical using an acridinium photocatalyst induced by visible light under air atmosphere at room temperature.It employs no metal or external oxidant for the synthesis of9-arylpurine derivatives.
文摘The aim of this study was to determine the time course of changes in extracellular fluid (ECF) concentrations of purines, amino acids, monoamines, and their metabolites in the striatum of rats during ischemia and reperfusion, using intracerebral microdialysis as the sampling technique. In rats subjected to 20 min forebrain ischemia by four-vessel occlusion, the concentrations of adenosine (Ade), inosine (Ino) and hypoxanthine (Hyp) were found to rise markedly. These changes were accompanied by dramatically elevated levels of aspartate (Asp), glutamate (Glu), taurine (Tau), γ-aminobutyric acid (GABA), dopamine (DA) and norepinephrine (NE), all of which gradually returned to baseline following reperfusion. Concomitantly, the levels of metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) . homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA) and xanthine (Xan) decreased during ischemia and gradually recovered 60～ 90 min after reperfusion. It was concluded that during global brain ischemia, the ECF is flooded with both potentially harmful (e. g. Asp, Glu, DA) and protective (e. g. Tau, GABA, Ade) agents.
基金the Key Project of Research and Development Plan of Ningxia(2020BFH02005)the Program of Introducing Talents of Discipline to Universities(111 Project)(111-2-06),for providing financial support。
文摘As a vital microorganism during Huangjiu fermentation,fungi have not been thoroughly evaluated for their potential rela-tionship with total purine levels in Huangjiu,which is a major contributing factor to hyperuricemia(HUA)and gout.In this study,we revealed the correlation between the succession of fungal communities and total purine content during Huangjiu fermentation.Our results demonstrated a continuous increase in total purine content during fermentation,rising from 13.08 to 72.12 mg/L.We observed significant dynamic changes in fungal community composition and diversity throughout the fermentation process,with the highest fungal species richness occurring on the third day.At the phylum level,Ascomycota dominated throughout fermentation(92.5-97.4%).At the genus level,the predominant taxa were Aspergillus(42.5-73.5%),Saccharomyces(0.0-41.1%),and Paecilomyces(0.0-16.9%),with Aspergillus dominating during the initial phase(0-3 days)and Saccharomyces becoming predominant in later stages(6-18 days).Correlation analysis revealed that Saccharomyces cerevisiae showed a strong positive correlation with total purine levels(r=0.73),while Aspergillus intermedius(r=−0.79)and Aspergillus flavus(r=−0.70)exhibited significant negative correlations.Furthermore,we identified that predominant fungal genera participate in purine metabolism.This study enhances our scientific understanding of purine formation mechanisms in Huangjiu and provides a foundation for developing targeted strategies to regulate purine content in future industrial production.
基金funded by Al Jalila Foundation-Research Grant(AJF2023-078)to SSMS.
文摘Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabolism,in the aggressiveness and metastatic behavior of BC.Methods:A comprehensive analysis was performed using in silico transcriptomic data(n=2509 patients),immunohistochemical profiling of BC tissues(n=103),and validation through western blotting in multiple BC cell lines.Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource(TIMER),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and the cBioPortal for cancer genomics(cBioPortal)platforms.Correlations between PNP and key epithelial–mesenchymal transition(EMT)markers,molecular subtypes,tumor grades,and stages were examined.Results:PNP was significantly overexpressed in human epidermal growth factor receptor 2(HER-2)-positive and triple-negative BCs compared to luminal subtypes.High PNP levels were strongly associated with advanced BC stages,high-grade tumors,EMT phenotypes,and poor overall survival.Notably,HER-2 inhibition suppressed PNP expression,while PNP gene silencing induced HER-2 upregulation,revealing a reciprocal regulatory loop.Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.Conclusion:Collectively,PNP emerges as a promising biomarker of BC aggressiveness and progression.Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target.Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.
基金Supported by National Natural Science Foundation of China(No.81590951,81373559,81373561 and 81573885)the State Key Program for Basic Research of China(No.2012CB518501)the Project of the Second Clinical Medical College of Nanjing University of Chinese Medicine(No.RLZZ201605)
文摘Objective: To quantify the purine concentrations of the acupoints along the pericardium and nonpericardium meridians under healthy and myocardial ischemia conditions to investigate the relationship between acupoint purine change and body functional status in rats.Methods: A total of 70 rats underwent an operation for myocardial ischemia,while 40 of them survived.They were randomly assigned to the following 5 subgroups:Neiguan(PC 6),Quze(PC 3),Tianquan(PC 2),Quchi(LI 11),and Jianyu(LI 15).Simultaneously,another40 healthy rats were also randomized into the same 5 subgroups as the control group.The tissue ?uids at the acupoints were collected by microdialysis for 30 min.Subsequently,the concentration of adenosine triphosphate(ATP),adenosine diphosphate(ADP),adenosine monophosphate(AMP),and adenosine(ADO) were quanti?ed using the high-performance liquid chromatography method.Results: Compared with the healthy group,the ADO at PC 6(P=0.012),PC 3(P=0.038),PC 2(P=0.024),and LI 15(P=0.042) obviously increased in the model group,while no signi?cant difference was observed at LI 11(P=0.201).However,ATP,ADP,and AMP manifested no significant changes in these areas,except for ATP at LI 15(P=0.036).Conclusions: Myocardial ischemia could induce an increase in ADO at acupoints of the upper arm and shoulder area,suggesting that the body functional status could affect the responsiveness of acupoints.The status of these acupoints could be pathogenically activated by disease,and distribution following some speci?c courses.
基金supported by the National Natural Science Foundation of China(No.32122069)Beijing Outstanding Young Scientist Program(No.BJJWZYJH01201910011025)China Postdoctoral Science Foundation(No.2023M730134)。
文摘Globally,hyperuricemia is a growing health,social,and economic problem which could cause gout,chronic kidney diseases and other diseases.There are increasing evidences that a sensible diet makes sense to reduce the risk of hyperuricemia.This review aims to explore the metabolic mechanism of dietary factors and effects of dietary types associated with hyperuricemia.Recommendations for dietary modification to prevent hyperuricemia are as following:decreasing intake of animal organs,seafood,sugar-sweetened,and alcohol beverages is essential;choosing water or unsweetened tea and coffee instead of sweetened beverages is beneficial;and increasing intake of vegetables,reduced-fat dairy products,foods containing fiber,micronutrients and unsaturated fatty acids is helpful.In addition,consumption of fruits and legumes in moderation is advantageous,and low-fructose of fruits and low-purine of non-soy beans are recommended.Moreover,personalized diet needs to be emphasized for hyperuricemic patients accompanied with diverse metabolic diseases.
基金funded by the National Key Research and Development Program of China(2022YFA1304200)the Beijing Natural Science Foundation(6222032)the Starting Grants Program for Young Talents at China Agricultural University,the 2115 Talent Development Program of China Agricultural University,and Chinese Universities Scientific Fund.
文摘Probiotics have been demonstrated to be effective and safe for hyperuricemia(HUA)and gout treatment.Hence,identifying microbes with high uric acid-or purine-metabolizing ability is highly important.Due to the high load of uric acid in chicken feces,we hypothesized that the chicken gut would be an excellent source for new uric acid or purine-metabolizing microbes.In this study,we examined chicken gut contents to isolate an Enterococcus faecalis strain(designated CML390)that displayed high uric acid-degrading ability.In vitro experiments indicated that E.faecalis CML390 could effectively metabolize uric acid under both aerobic and anaerobic conditions,and the richer the nutrients,the higher the rate of uric acid degradation.By integrating genomics,transcriptomics,and metabolomics analyses,we revealed two pathways involved in aerobic and anaerobic uric acid degradation,respectively,in this isolate.E.faecalis CML390 relies on oxygen to metabolize uric acid into substances such as allantoin under aerobic conditions,while it also harbors a conserved uric acid-inducible gene cluster for anaerobic uric acid metabolism.An in vivo experiment showed that gavage with live E.faecalis CML390 in a mouse model of HUA(established using a combination of uric acid and potassium oxonate)significantly reduced serum uric acid levels and alleviated HUA.Our findings contribute to the exploration of the pathways and mechanisms of uric acid metabolism in intestinal microorganisms and provide a candidate probiotic for the treatment of HUA and gout.
基金supported by grants from the National Natural Science Foundation of China(32270290)the Shanghai Engineering Research Center of Plant Germplasm Resources(17DZ2252700).
文摘Plant height is an important trait that affects the crop yield and overall productivity.The Green Revolution,which began in the 1960s,brought about a remarkable surge in grain production,largely credited to the introduction of new wheat(Triticum aestivum)and rice(Oryza sativa)varieties,specifically the dwarf variants.Short plants offer several advantages,including denser planting,resistance to lodging,and easier application of fertilizers or fungicides(Stokstad,2023).
文摘Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.
基金supported by CAPESFaperj+1 种基金CNPq‘‘National Institute of Science and Technology for Regenerative Medicine”, CNPq, Brazil(to AMBM)
文摘Injuries to the spinal cord result in permanent disabilities that limit daily life activities.The main reasons for these poor outcomes are the limited regenerative capacity of central neurons and the inhibitory milieu that is established upon traumatic injuries.Despite decades of research,there is still no efficient treatment for spinal cord injury.Many strategies are tested in preclinical studies that focus on ameliorating the functional outcomes after spinal cord injury.Among these,molecular compounds are currently being used for neurological recovery,with promising results.These molecules target the axon collapsed growth cone,the inhibitory microenvironment,the survival of neurons and glial cells,and the re-establishment of lost connections.In this review we focused on molecules that are being used,either in preclinical or clinical studies,to treat spinal cord injuries,such as drugs,growth and neurotrophic factors,enzymes,and purines.The mechanisms of action of these molecules are discussed,considering traumatic spinal cord injury in rodents and humans.
基金The National Natural Science Foundation of China(20173040)
文摘The separation of a group of 17 purine and its derivatives by capillary zone electrophoresis is presented. A systematic approach was used to study the effect of pH, buffer type, organic modifiers, applied potential, sodium dodecyl sulfate (SDS) and cyclodextrins on the separation of these purine derivatives. An ideal condition was found for their separation, which was 30 mmol/L sodium borate buffer (pH 9–9.5), 10%(V/V) methanol buffer modifier and 20 kV. Under this condition, the 17 purine derivatives were baseline separated and the linear correlation coefficient for adenine, uric acid and 2-thioxanthine was 0. 99 over two orders of magnitude. The variation of peak areas was less than 4. 6%(n=5) and that of migration times was in the range of 0%–3%, while the samples were injected hydrodynamically at a height of 15 cm and an injection time of 8–10 s. In addition, alcohol, 1-propanol, 1-butanol and acetonitrile were also effective additives in the separation. However, SDS and various β-cyclodextrin (β-CDs) were found to do no good to their separation.
基金Supported by the Innovation Fund for Technology Based Firms from Ministry of Science and Technology of China(07C26213101283)
文摘The chemical synthesis of Guanine arabinoside （ara-G） is extremely complex, time-consuming, and seriously polluted. A two-step enzymatic synthesis process was developed to acquire ara-G easily. 2,6-Diaminopurine arabinoside （ara-DA） was first synthesized with purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase produced by Enterobacter aerogenes DGW-07. The conversion yield of ara-DA could reach above 90% when the reaction liquid contained 30 mmol·L^-1 uracil arabinoside as arabinose donor, 10 mmol·L^- 1 2,6-diaminopurine as arabinose acceptor in pH 7.0 20 mmol·L^-1 phosphate buffer, and reacted at 60℃ for 48h. Then, ara-DA was effectively transformed into ara-G with adenylate deaminase produced by Aspergillus oryzae DAW-01. The total process had no complex separation and purification.
基金supported by the Key Transgenic Breeding Program of the Ministry of Agriculture and Rural Affairs of China(2016ZX08009003-003-008)the National Natural Science Foundation of China(31971921,U20A2030)the State Key Laboratory of Rice Biology,China(20200102)。
文摘Xanthine dehydrogenase, a member of the molybdenum enzyme family, participates in purine metabolism and catalyzes the generation of ureides from xanthine and hypoxanthine. However, the mechanisms by which xanthine dehydrogenase affects rice growth and development are poorly understood. In the present study, we identified a mutant with early leaf senescence and reduced tillering that we named early senescence and less-tillering 1(esl1). Map-based cloning revealed that ESL1 encodes a xanthine dehydrogenase, and it was expressed in all tissues. Chlorophyll content was reduced and chloroplast maldevelopment was severe in the esl1 mutant. Mutation of ESL1 led to decreases in allantoin, allantoate, and ABA contents. Further analysis revealed that the accumulation of reactive oxygen species in esl1 resulted in decreased photosynthesis and impaired chloroplast development, along with increased sensitivity to abscisic acid and abiotic stresses. Ttranscriptome analysis showed that the ESL1 mutation altered the expression of genes involved in the photosynthesis process and reactive oxygen species metabolism.Our results suggest that ESL1 is involved in purine metabolism and the induction of leaf senescence.These findings reveal novel molecular mechanisms of ESL1 gene-mediated plant growth and leaf senescence.
基金supported by the National Natural Science Foundation of China(NSFC)(31900310 to R.T.)Key Project of the NSFC(32030011 and 31630071 to G.Y.)+2 种基金NSFC(31950410545 to I.S.)Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Jiangsu Specially-Appointed Professors Program(to I.S.)。
文摘Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabolism is an essential response to oxidative stress, and an imbalance between purine salvage and de novo biosynthesis pathways can generate damaging reactive oxygen species(ROS). Here, we examined the evolution of 117 purine metabolism-related genes to explore the accompanying molecular mechanisms of enhanced purine metabolism in mammals under high oxidative stress. We found that positively selected genes,convergent changes, and nonparallel amino acid substitutions are possibly associated with adaptation to oxidative stress in mammals. In particular, the evolution of convergent genes with c AMP and c GMP regulation roles may protect mammals from oxidative damage. Additionally, 32 genes were identified as under positive selection in cetaceans, including key purine salvage enzymes(i.e., HPRT1), suggesting improved re-utilization of non-recyclable purines avoid hypoxanthine accumulation and reduce oxidative stress. Most intriguingly, we found that six unique substitutions in cetacean xanthine dehydrogenase(XDH), an enzyme that regulates the generation of the ROS precursor xanthine oxidase(XO) during ischemic/hypoxic conditions, show enhanced enzyme activity and thermal stability and diminished XO conversion activity. These functional adaptations are likely beneficial for cetaceans by reducing radical oxygen species production during diving. In summary, our findings offer insights into the molecular and functional evolution of purine metabolism genes in mammalian oxidative stress adaptations.
文摘FT Ⅰ (AAAAGGGGAAGCAGAG), a poly purine ele-ment within the myloid-lineage specific enhancer (En 1) of the mouse myeloperoxidase gene [1, 2] has been fur-ther characterised. 1, FT Ⅰ functions as a myeloid-lineage specific transcription regulatory element; 2, WEHI 3BD+ cells have higher binding activity to FT Ⅰ and express the proteins which could form the unique DNA-protein com-plex(es) of FT Ⅰ;. 3, The essential sequence for the specific DNA-protein interactions of FT Ⅰ is AAAAGGGGAAGC; 4, South-western analysis in conjunction with the compe-tition assay of the proteins binding to FT Ⅰ, has revealed a 28 kd protein in WEHI 3BD+ cells that displays the properties of the putative transcription factor which acts through FT Ⅰ. These new findings have demonstrated both the functional myeloid-lineage specificity and the novelty of FT Ⅰ.
基金Supported by The National Natural Science Foundation of China,No.31671192 and No.31571180Foundation of Xin Hua Hospital,No.JZPI201708
文摘AIM To investigate the distribution and function of interstitialcells of Cajal(ICCs) and platelet-derived growth factor receptor-α positive(PDGFRα+) cells in the proximal and distal colon.METHODS The comparison of colonic transit in the proximal and distal ends was performed by colonic migrating motor complexes(CMMCs). The tension of the colonic smooth muscle was examined by smooth muscle spontaneous contractile experiments with both ends of the smooth muscle strip tied with a silk thread. Intracellular recordings were used to assess electrical field stimulation(EFS)-induced inhibitory junction potentials(IJP) on the colonic smooth muscle. Western blot analysis was used to examine the expression levels of ICCs and PDGFRα in the colonic smooth muscle.RESULTS Treatment with NG-nitro-L-arginine methyl ester hydrochloride(L-NAME) significantly increased the CMMC frequency and spontaneous contractions, especially in the proximal colon, while treatment with MRS2500 increased only distal CMMC activity and smooth muscle contractions. Both CMMCs and spontaneous contractions were markedly inhibited by NPPB, especially in the proximal colon. Accordingly, CyPPA sharply inhibited the distal contraction of both CMMCs and spontaneous contractions. Additionally, the amplitude of stimulationinduced nitric oxide(NO)/ICC-dependent slow IJPs(sIJPs) by intracellular recordings from the smooth muscles in the proximal colon was larger than that in the distal colon, while the amplitude of electric field stimulationinduced purinergic/PDGFRα-dependent fast IJPs(fIJPs) in the distal colon was larger than that in the proximal colon. Consistently, protein expression levels of c-Kit and anoctamin-1(ANO1) in the proximal colon were much higher, while protein expression levels of PDGFRα and small conductance calcium-activated potassium channel 3(SK3) in the distal colon were much higher.CONCLUSION The ICCs are mainly distributed in the proximal colon and there are more PDGFRα+ cells are in the distal colon, which generates a pressure gradient between the two ends of the colon to propel the feces to the anus.
