[Objective] This study aimed to investigate the characteristics of deposition of inosine monophosphate （IMP） and intramuscular fat （IMF） in muscles of Jinghai yellow chickens and its crossbred.[Method] The charact...[Objective] This study aimed to investigate the characteristics of deposition of inosine monophosphate （IMP） and intramuscular fat （IMF） in muscles of Jinghai yellow chickens and its crossbred.[Method] The characteristics of IMP and IMF deposition of 112-day-old Jinghai yellow chickens （J×J） and its two different 70-day- old crossbreeds （J×B and B×B） were analyzed. The IMP content in breast muscle and leg muscle were determined by HPLC. [Result] The contents of IMP and cor- rected inosine monophosphate （IMPc） in breast muscle were significantly or ex- tremely significantly higher than that in leg muscle of the chickens in the three groups whether in male or female chickens （P〈0.05 or P〈0.01）. There were no sig- nificant difference in the contents of IMP and IMPc between hens and roosters （P〉 0.05）. The fresh degree of breast muscle and leg muscle was 96,11%-98.16% and 87.22%-93.07%, respectively. And the fresh degree of breast muscle was higher than that of leg muscle. In the three groups, the IMF content in leg muscle was significantly higher than that in breast muscle whether in male or female chickens （P〈0.05）. The contents of IMF in breast muscle and leg muscle were 0.36%-0.75% and 1.84%-2.38%, respectively. The iMP content in breast muscle of chickens in Bx J group was extremely significantly higher than that in breast muscle of chickens in JxJ group （P〈0.01）, but the contents of IMPc and iMF of breast muscle and leg muscle of the chickens in the three groups had no significant difference （P〉0.05）. [Conclusion] To sum up, the freshness and flavor significantly differ between the breast muscle and leg muscle of chickens, but show no significant difference among the three groups.展开更多
AIM: To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA ) polymorphism in Egyptian chronic hepatitis C virus (HCV) patients.METHODS:The human genomic DNA of all pati...AIM: To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA ) polymorphism in Egyptian chronic hepatitis C virus (HCV) patients.METHODS:The human genomic DNA of all patients was extracted from peripheral blood cells in order to determine the single nucleotide polymorphism (SNP) of ITPA (rs1127354). SNP genotyping was performed by real time polymerase chain reaction (PCR, ABI TaqMan allelic discrimination kit) for 102 treatment-naive Egyptian patients with chronic HCV. All patients had no evidence of cardiovascular or renal diseases. They received a combination treatment of pegylated interferon α (PEG-IFNα) as a weekly subcutaneous dose plus an oral weight-adjusted dose of ribavirin (RBV). The majority received PEG-IFNα2a (70.6%) while 29.4% received PEG-IFNα2b. The planned duration of treatment was 24-48 wk according to the viral kinetics throughout the course of treatment. Pre-treatment liver biopsy was done for each patient for evaluation of fibrosis stage and liver disease activity. The basal viral load level was detected quantitatively by real time PCR while viral load throughout the treatment course was performed qualitatively by COBAS TaqMan assay. RESULTS: Ninety-three patients (91.2%) had ITPA SNP CC genotype and 9 (8.8%) had non-CC genotype (CA and AA). The percentage of hemoglobin (Hb) decline was higher for CC patients than for non-CC patients, particularly at weeks 4 and 8 (P=0.047 and 0.034, respectively). During the first 12 wk of treatment, CC patients had significantly more Hb decline > 3 g/dL than non-CC patients: 64.5% vs 22.2% at weeks 8 and 12, respectively, (P=0.024 and 0.038). Reduction of the amount of the planned RBV dose was significantly higher for CC patients than non-CC patients during the first 12 wk (18% ± 12.1% vs 8.5% ± 10.2%, P=0.021). The percentage of CC patients with RBV dose reduction was significantly greater than that of non-CC patients (77.4% vs 44.4%, P=0.044). Multivariate analysis identified only the percentage of RBV dose as a predictor for Hb decline. Platelet decline was significantly higher in non-CC patients than CC patients at weeks 12, 24 and 48 (P=0.018, 0.009 and 0.026, respectively). CONCLUSION: Rs1127354 ITPA polymorphism plays a decisive role in protecting against treatment-induced anemia and the need for RBV dose reduction in Egyptian HCV patients.展开更多
We investigated the relationship between muscle inosine monophosphate (IMP) content and mRNA levels of ADSL, AMPD1, and ATIC in Dapulian (DPL), Landrace × Dapulian (LDPL), and Duroc × Landrace × Dapulia...We investigated the relationship between muscle inosine monophosphate (IMP) content and mRNA levels of ADSL, AMPD1, and ATIC in Dapulian (DPL), Landrace × Dapulian (LDPL), and Duroc × Landrace × Dapulian (DLDPL) hybridized pigs. Methods: The total RNA in longissimus dorsi was isolated from Dapulian (DPL), Landrace × Dapulian (LDPL) and Duroc × Landrace × Dapulian (DLDPL) hybridized pigs, weighed about 95.0 kg, n = 8/species. The internal genes with highest stability (YWHAZ and RPL4) were chosen from 11 common internal genes using Quantitative real-time PCR (qPCR) and geNorm software. The mRNA levels of ADSL, AMPD1 and ATIC genes were corrected with YWHAZ and RPL4 genes. The muscular IMP content was determined by HPLC. The muscular IMP content in DPL was higher than that in LDPL and DLDPL, 25.00% (p 0.05) and 15.56% (p > 0.05), respectively. The muscular mRNA level of ADSL gene in DPL and LDPL was higher than that in DLDPL, 24.14% and 12.07%, respectively (p 0.05). The muscular mRNA level of ATIC gene in DPL and LDPL was higher than that in DLDPL, 66.67% and 33.33%, respectively (p 0.05). The muscular mRNA level of AMPD1 gene in DPL and LDPL was higher than that in DLDPL, 14.49% and 33.26%, respectively. Furthermore, the IMP content was positively correlated with the mRNA level of ADSL, AMPD1 and ATIC genes, respectively (p 0.05). The mRNA level of ADSL gene was highly related to that of AMPD1 and ATIC gene, respectively (p 0.01), while that of AMPD1 gene was not strongly correlated with that of ATIC gene (p > 0.05). The muscular mRNA level of AMPD1, ADSL and ATIC genes and the muscular IMP content in DPL were highest, followed by those in LDPL and DLDPL. The muscular IMP content was positively correlated with the muscular mRNA level of ADSL, AMPD1 and ATIC genes, respectively.展开更多
Inosine is a vital RNA modification across three kingdoms of life.It has been demonstrated that inosine plays important roles in modulation of the fate of RNAs.In the current study,we developed a highly sensitive meth...Inosine is a vital RNA modification across three kingdoms of life.It has been demonstrated that inosine plays important roles in modulation of the fate of RNAs.In the current study,we developed a highly sensitive method to determine inosine in a single cell by N-cyclohexyl-N’-β-(4-methylmorpholinium)ethylcarbodiimide p-toluenesulfonate(CMCT)derivatization in combination with mass spectrometry analysis.The results showed that the detection sensitivity of inosine was increased by 556-fold after CMCT derivatization,with the limit of detection(LOD)being 4.5 amol.With the established method,we could detect inosine from 13.0 pg of total RNA of HEK293T cells.Meanwhile,inosine in RNA from a single cell could also be clearly detected due to the improved detection sensitivity.Moreover,we found the level of inosine in RNA of sleep-deprived mice was significantly increased compared to the control mice,indicating that inosine is associated with sleep behavior and might be a potential indicator of sleep disorder.Taken together,the chemical derivatization coupled with mass spectrometry analysis offers a valuable tool in determination of endogenous RNA modifications in a single cell,which should benefit the functional study of RNA modification in rare clinical samples.展开更多
6-Thioguanine(6TG)is a widely used chemotherapeutic agent for the treatment of a variety of human diseases including acute lymphoblastic leukemia.After entry into cells,6TG is metabolically converted into 6-thioguanos...6-Thioguanine(6TG)is a widely used chemotherapeutic agent for the treatment of a variety of human diseases including acute lymphoblastic leukemia.After entry into cells,6TG is metabolically converted into 6-thioguanosine(^(S)G)nucleotide that can be incorporated into the genome during DNA replication.^(S)G in genomic DNA could induce cell death by triggering the post-replicative mismatch repair(MMR)pathway.Meanwhile,incorporation of 6TG into the Cp G sites could perturb the global DNA methylation and gene regulation.However,the effect of 6TG on RNA modifications is still unknown.Adenosine-toinosine(A-to-I)editing in RNA is one of the most common post-transcriptional modifications in mammals and there is growing evidence showing the significant alteration of A-to-I RNA editing in tumor tissues compared to normal tissues.In the current study,we examined the incorporation of 6TG into RNA and investigated its effect on A-to-I editing of bladder cancer-associated protein(BLCAP)transcript in acute lymphoblastic leukemia cells.The results demonstrated that ^(S)G could be incorporated into various RNA species,with m RNA having the most abundant ^(S)G.In addition,the results showed 6TG treatment elevated A-to-I editing in BLCAP transcript through upregulating adenosine deaminase 2 acting on RNA(ADAR2),which eventually contributes to the decreased cell viability.This study highlights a new mechanism of the cytotoxicity of 6TG in inducing cell death.展开更多
A 6-pyridinium salt(2)was obtalned from 2',3',5'-tri-O-acetyhnosine by use of phosphoryl chloride as the condensmg agent.The conversion of salt(2)into 6-(2- methylphenoxy)-purinenucleoside(3)denvatives und...A 6-pyridinium salt(2)was obtalned from 2',3',5'-tri-O-acetyhnosine by use of phosphoryl chloride as the condensmg agent.The conversion of salt(2)into 6-(2- methylphenoxy)-purinenucleoside(3)denvatives under mild condition is also described.展开更多
[ Objective] The paper was to investigate the degradation and deposition changes of inosine monophosphate （IMP） and its metabolites in muscle of lean pigs and crossbreeding pigs under cold storage condition at 4℃. ...[ Objective] The paper was to investigate the degradation and deposition changes of inosine monophosphate （IMP） and its metabolites in muscle of lean pigs and crossbreeding pigs under cold storage condition at 4℃. [ Method] The contents of IMP and its metabolites in longissimus dorsi of lean pigs and crossbreeding pigs were determined by HPLC method. [ Result] Duroc, Landrace, Yorkshire and DLY pigs shared the same degradation and deposition pattern on IMP, inosine and hypoxanthine. On the second day of cold storage, the content of IMP reached the maximum value, which increased by 0.4% - 15.32% compared with the first day, and then it started to decline. On the fourth day of cold storage, the content of IMP significantly reduced by 23.81% - 39.06% than that on the second day. On the fifth and sixth day of cold storage, the content of IMP kept on falling down slowly and maintained around 1.0 mg/g. While the contents of inosine and hypoxanthine showed an increasing tendency with the extension of cold storage time. [ Conclusion ] Lean pigs Duroc, Landraee and Yorkshire and DLY three- way crossbreeding pigs shared the same degradation and deposition pattern on IMP and its metabolites. With the extension of cold storage, the content of IMP first increased then gradually decreased; while inosine and hypoxanthine gradually increased, and the difference among breeds was not significant.展开更多
Inosine monophosphate(IMP),as a critical umami substance,is one of the most important indicators for evaluating the quality of meat products.Here,a sensitive electrochemiluminescence(ECL)biosensor based on graphdiyne(...Inosine monophosphate(IMP),as a critical umami substance,is one of the most important indicators for evaluating the quality of meat products.Here,a sensitive electrochemiluminescence(ECL)biosensor based on graphdiyne(GDY)/AuNPs/luminol nanocomposites was constructed to detect IMP.The GDY/AuNPs/luminol nanocomposites were synthesized by using simple one-pot method.GDY utilized its 2D framework to disperse and fix gold nanoparticles,which inhibited the agglomeration of gold nanoparticles and greatly improved its stability and catalytic properties.Importantly,GDY/AuNPs/luminol nanocomposites showed excellent catalytic ability and superior ECL activity towards luminol-H_(2)O_(2) systems due to the synergistic effect of GDY and AuNPs.Under optimal conditions,the prepared biosensor exhibited a wide linear range from 0.01 g/L to 20 g/L,a satisfactory limit detection of 0.0013 g/L,as well as an excellent specificity.Moreover,we carried out the precise analysis of IMP in actual meat samples with acceptable results compared to the liquid chromatography.We believe that this work could offer an efficient ECL platform for accurate and reliable report of IMP levels,which is significant for maintaining food quality and safety.展开更多
BACKGROUND: It has been demonstrated that adenosine can induce glial cell to release cytochrome C, enhance expression of apoptotic gene bax, inhibit anti-apoptotic gene bcl-2, and activate caspase-3 to apoptosis; Wher...BACKGROUND: It has been demonstrated that adenosine can induce glial cell to release cytochrome C, enhance expression of apoptotic gene bax, inhibit anti-apoptotic gene bcl-2, and activate caspase-3 to apoptosis; Whereas inosine can inhibit neuronal apoptosis which is similar to bcl-2. OBJECTIVE: To observe the effects of inosine on neuronal apoptosis and expression of cytochrome C mRNA in rats after focal cerebral ischemia/reperfusion, and analyze the pathway of its neuroprotective effect. DESIGN: A randomised controlled animal trial. SETTINGS: Department of Neurology, Rongcheng Second People's Hospital; Department of Neurology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. MATERIALS: Sixty-eight rats, weighing 230-280 g and clean grade, were used. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and cytochrome C mRNA in situ hybridization kits and DAB staining kit were purchased from Wuhan Boster Biological Co., Ltd.; Inosine injection [200 mg (2 mL) each] from Qingdao First Pharmaceutical Factory. METHODS: The experiment was accomplished in the animal experimental center in Tongji Medical College of Huazhong University of Science and Technology from December 2003 to June 2005. ① Sixty-four rats were made into focal ischemia by middle cerebral artery occlusion (MCAO) with a nylon monofilament suture. The successfully induced rats were assigned to inosine group (n =32) and model group (n =32) at random. Rats in the inosine group were intraperitoneally administrated with inosine in dose of 100 mg/kg preoperatively, twice a day, 7 days in all. The rats in the control group were injected with the same dose of saline solution by the similar way preoperatively. Each group was randomized into ischemia /reperfusion 2, 6, 12, 24 hours, 2, 3, 7 and 14 days subgroups consisted of 4 rats. The other 4 rats were taken as the sham-operated group, the rats were given the same treatment except for not introduced the filament into the external carotid artery stump, and brain tissue was removed at 2 hours of reperfusion. ② In situ hybridization was performed to examine the expression of cytochrome C mRNA while TUNEL staining was made to characterize apoptosis. ③ The t test was used to compare the difference of measurement data. MAIN OUTCOME MEASURES: ① Neuronal apoptosis in the different regions of the ischemic brain tissue; ② Expression of cytochrome C mRNA in the different regions at different time points after MCAO. RESULTS: All the 68 rats were involved in the analysis of results. ① Neuronal apoptosis: A small number of TUNEL-positive cells were detected in the sham-operated brain and non-ischemic brain. The number of apoptotic cells in the ischemic cortex peaked at 24 hours of reperfusion [(72.00±1.98) cells] and that in the striatum peaked at 2 days [(94.75±3.57) cells], then decreased to the level of sham-operated group at 14 days. Inosine could reduce apoptotic cells from 12 hours to 7 days of reperfusion as compared with the model group (t =6.19-26.67, P < 0.01). ② Cytochrome C mRNA expression: There was weak expression of cytochrome C mRNA in both sham-operated brain and contralateral brain. Cytochrome C was detected at 2 hours of reperfusion in ischemic brain [(25.75±3.50), (39.75±2.49) cells], and strongly increased to a peak at 12 hours and 24 hours of reperfusion in cortex and striatum [(122.50±6.69), (119.25±5.12) cells], respectively. Furthermore, inosine could significantly decrease cytochrome C expression in cortex at 12 hours to 14 days of reperfusion after ischemic reperfusion and that in striatum at 12 hours to 3 days (t =8.67-43.26, P < 0.01). CONCLUSION: Inosine can exert a neuroprotective effect by inhibiting apoptosis and cytochrome C mRNA expression.展开更多
The adsorption characteristics of inosine from fermentation solution on anion exchange resin under the condition of different PH, resin type are investigated. Besides 3 the desorption conditions are studied under diff...The adsorption characteristics of inosine from fermentation solution on anion exchange resin under the condition of different PH, resin type are investigated. Besides 3 the desorption conditions are studied under different temperature.The adsorption and desorption mechanism are described to obtain the optimumtechnological condition of inosine extraction.展开更多
This is a correction to:Hao Cheng,Jun Yu,Chi Chun Wong,Adenosine-to-inosine RNA editing in cancer:molecular mechanisms and downstream targets,Protein&Cell,2024;https://doi.org/10.1093/procel/pwae039 In the origina...This is a correction to:Hao Cheng,Jun Yu,Chi Chun Wong,Adenosine-to-inosine RNA editing in cancer:molecular mechanisms and downstream targets,Protein&Cell,2024;https://doi.org/10.1093/procel/pwae039 In the originally published version of the manuscript there were errors in Figure 2.In panel H,text should read:"Loses capacity"instead of:"oses capacity";a redundant letter"I"that was highlighted should be removed.展开更多
Purines are building blocks for DNA and RNA,found as the energy currency of cells(ATP and GTP),used as signaling molecules(cGMP,cAMP and ATP),and served as precursors for synthesizing primary products such as polysacc...Purines are building blocks for DNA and RNA,found as the energy currency of cells(ATP and GTP),used as signaling molecules(cGMP,cAMP and ATP),and served as precursors for synthesizing primary products such as polysaccharides,sucrose,and phospholipids as well as secondary products(Stasolla et al.,2003;Pareek et al.,2020).Thus,the synthesis of purines is a critical pathway in the cells of all living organisms.Purines can be synthesized through two pathways:de novo and salvage(Stasolla et al.,2003).Recent investigations revealed that purine synthesis is vital for the proper development of chloroplasts in plants.In Arabidopsis,CIA1 encodes the enzyme glutamine phosphoribosyl pyrophosphate amidotransferase,which catalyzes the first committed step of purine de novo biosynthesis,the loss-of-function mutant cia1 shows small,pale-green mosaic leaves(Hung et al.,2004).In rice,both VAL1 and GARS encode glycinamide ribonucleotide synthetase that mediates the second step in purine biosynthesis.展开更多
RNA contains diverse post-transcriptional modifications,and its catabolic breakdown yields numerous modified nucleosides requiring correct processing,but the mechanisms remain unknown.Here,we demonstrate that three RN...RNA contains diverse post-transcriptional modifications,and its catabolic breakdown yields numerous modified nucleosides requiring correct processing,but the mechanisms remain unknown.Here,we demonstrate that three RNA-derived modified adenosines,N6-methyladenosine(m6A),N6,N6-dimethyladenosine(m6,6A),and N6-isopentenyladenosine(i6A),are sequentially metabolized into inosine monophosphate(IMP)to mitigate their intrinsic cytotoxicity.展开更多
In a recent publication in Cell,Stevens et al.uncovered that microbiota disruptions reduced inosine levels and impaired CD8^(+)T cell immunity against influenza infection in early life.Treatment with inosine-producing...In a recent publication in Cell,Stevens et al.uncovered that microbiota disruptions reduced inosine levels and impaired CD8^(+)T cell immunity against influenza infection in early life.Treatment with inosine-producing bacteria or inosine alone restored T cell responsiveness through a nuclear factor interleukin 3(NFIL3)-dependent mechanism.展开更多
The functional impact of modifications of cellular RNAs,including m RNAs,mi RNAs and lnc RNAs,is a field of intense study.The role of such modifications in cancer has started to be elucidated.Diverse and sometimes opp...The functional impact of modifications of cellular RNAs,including m RNAs,mi RNAs and lnc RNAs,is a field of intense study.The role of such modifications in cancer has started to be elucidated.Diverse and sometimes opposite effects of RNA modifications have been reported.Some RNA modifications promote,while ot-hers decrease the growth and invasiveness of cancer.The present manuscript reviews the current knowledge on the potential impacts of N6-Methyladenosine,Pse-udouridine,Inosine,2’O-methylation or methylcytidine in cancer’s RNA.It also highlights the remaining qu-estions and provides hints on research avenues and potential therapeutic applications,whereby modulating dynamic RNA modifications may be a new method to treat cancer.展开更多
An eco-friendly and fast HPLC method was developed for the determination of adenosine, inosine, guanosine and uridine in Cordyceps and related products(fermented mycelia of Hirsutella sinensis and Paecilomyces hepiali...An eco-friendly and fast HPLC method was developed for the determination of adenosine, inosine, guanosine and uridine in Cordyceps and related products(fermented mycelia of Hirsutella sinensis and Paecilomyces hepiali). The sample was ultrasonically extracted using 0.5% phosphoric acid solutions for 2.5 min. Sample separation was performed on a Poroshell SB-Aq column(50 mm × 4.6 mm, 2.7 μm) using eco-friendly mobile phase consisting of formic acid and ammonium formate aqueous solution at a flow rate of 1.0 m L·min;. The detection wavelength was 260 nm. The developed HPLC method showed good linearity with correlation coefficients of 1.0000 in the test range. Good precision, repeatability and stability of this method were also observed(RSD ≤ 2.81%).The recovery ranged from 91.84%-105.19%(RSD ≤ 2.59%). Compared with reported methods, the current method did not use harmful organic solvent and took only 10.5 min. It obtained a high eco-score of 91 by the "Analytical Eco-Scale" tool. The developed method is eco-friendly and fast, which is suitable for the quality evaluation of Cordyceps and related products.展开更多
Hyperuricemia is a critical threat to human health,and a high inosine diet can increase the prevalence of it.Lacticaseibacillus rhamnosus Fmb14 was isolated from traditional fermented Chinese yogurt,and its inosine de...Hyperuricemia is a critical threat to human health,and a high inosine diet can increase the prevalence of it.Lacticaseibacillus rhamnosus Fmb14 was isolated from traditional fermented Chinese yogurt,and its inosine degradation rate reached 36.3%at 109 CFU/mL for 24 h.LC-MS analysis revealed that high concentrations of inosine could activate compensatory metabolic pathways of L.rhamnosus Fmb14 to catalyse inosine as an energy source and produce intracellular folic acid and riboflavin.The contents of folic acid and riboflavin were 6.0 and 4.3 fold increased after inosine treatment in the cell-free extracts(CFE).L.rhamnosus Fmb14 CFE treatment ameliorates hyperuricemia through xanthine oxidase(XOD)inhibition and ATP-binding cassette subfamily G member 2(ABCG2)promotion,both of which are responsible for uric acid(UA)synthesis and secretion in HepG2 and Caco2 cells,respectively.The in vivo results showed that the serum UA level decreased from 236.28 to 149.28μmol/L after 8 weeks of oral administration of L.rhamnosus Fmb14 in inosine-induced hyperuricemia model mice.Our results revealed that L.rhamnosus Fmb14 has a potential as a biological therapeutic agent in hyperuricemia prevention.展开更多
基金Supported by the Science and Technology Supporting Project (Agriculture) of Jiangsu Province (BE2011452)the Special Fund Project of the National Broiler Industry Technology System (CARS-42-G23)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)~~
文摘[Objective] This study aimed to investigate the characteristics of deposition of inosine monophosphate （IMP） and intramuscular fat （IMF） in muscles of Jinghai yellow chickens and its crossbred.[Method] The characteristics of IMP and IMF deposition of 112-day-old Jinghai yellow chickens （J×J） and its two different 70-day- old crossbreeds （J×B and B×B） were analyzed. The IMP content in breast muscle and leg muscle were determined by HPLC. [Result] The contents of IMP and cor- rected inosine monophosphate （IMPc） in breast muscle were significantly or ex- tremely significantly higher than that in leg muscle of the chickens in the three groups whether in male or female chickens （P〈0.05 or P〈0.01）. There were no sig- nificant difference in the contents of IMP and IMPc between hens and roosters （P〉 0.05）. The fresh degree of breast muscle and leg muscle was 96,11%-98.16% and 87.22%-93.07%, respectively. And the fresh degree of breast muscle was higher than that of leg muscle. In the three groups, the IMF content in leg muscle was significantly higher than that in breast muscle whether in male or female chickens （P〈0.05）. The contents of IMF in breast muscle and leg muscle were 0.36%-0.75% and 1.84%-2.38%, respectively. The iMP content in breast muscle of chickens in Bx J group was extremely significantly higher than that in breast muscle of chickens in JxJ group （P〈0.01）, but the contents of IMPc and iMF of breast muscle and leg muscle of the chickens in the three groups had no significant difference （P〉0.05）. [Conclusion] To sum up, the freshness and flavor significantly differ between the breast muscle and leg muscle of chickens, but show no significant difference among the three groups.
基金Supported by A Grant–in-Aid for Comprehensive Research from the Ministry of Education, Culture, Sports Science and Technology of Japan
文摘AIM: To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA ) polymorphism in Egyptian chronic hepatitis C virus (HCV) patients.METHODS:The human genomic DNA of all patients was extracted from peripheral blood cells in order to determine the single nucleotide polymorphism (SNP) of ITPA (rs1127354). SNP genotyping was performed by real time polymerase chain reaction (PCR, ABI TaqMan allelic discrimination kit) for 102 treatment-naive Egyptian patients with chronic HCV. All patients had no evidence of cardiovascular or renal diseases. They received a combination treatment of pegylated interferon α (PEG-IFNα) as a weekly subcutaneous dose plus an oral weight-adjusted dose of ribavirin (RBV). The majority received PEG-IFNα2a (70.6%) while 29.4% received PEG-IFNα2b. The planned duration of treatment was 24-48 wk according to the viral kinetics throughout the course of treatment. Pre-treatment liver biopsy was done for each patient for evaluation of fibrosis stage and liver disease activity. The basal viral load level was detected quantitatively by real time PCR while viral load throughout the treatment course was performed qualitatively by COBAS TaqMan assay. RESULTS: Ninety-three patients (91.2%) had ITPA SNP CC genotype and 9 (8.8%) had non-CC genotype (CA and AA). The percentage of hemoglobin (Hb) decline was higher for CC patients than for non-CC patients, particularly at weeks 4 and 8 (P=0.047 and 0.034, respectively). During the first 12 wk of treatment, CC patients had significantly more Hb decline > 3 g/dL than non-CC patients: 64.5% vs 22.2% at weeks 8 and 12, respectively, (P=0.024 and 0.038). Reduction of the amount of the planned RBV dose was significantly higher for CC patients than non-CC patients during the first 12 wk (18% ± 12.1% vs 8.5% ± 10.2%, P=0.021). The percentage of CC patients with RBV dose reduction was significantly greater than that of non-CC patients (77.4% vs 44.4%, P=0.044). Multivariate analysis identified only the percentage of RBV dose as a predictor for Hb decline. Platelet decline was significantly higher in non-CC patients than CC patients at weeks 12, 24 and 48 (P=0.018, 0.009 and 0.026, respectively). CONCLUSION: Rs1127354 ITPA polymorphism plays a decisive role in protecting against treatment-induced anemia and the need for RBV dose reduction in Egyptian HCV patients.
文摘We investigated the relationship between muscle inosine monophosphate (IMP) content and mRNA levels of ADSL, AMPD1, and ATIC in Dapulian (DPL), Landrace × Dapulian (LDPL), and Duroc × Landrace × Dapulian (DLDPL) hybridized pigs. Methods: The total RNA in longissimus dorsi was isolated from Dapulian (DPL), Landrace × Dapulian (LDPL) and Duroc × Landrace × Dapulian (DLDPL) hybridized pigs, weighed about 95.0 kg, n = 8/species. The internal genes with highest stability (YWHAZ and RPL4) were chosen from 11 common internal genes using Quantitative real-time PCR (qPCR) and geNorm software. The mRNA levels of ADSL, AMPD1 and ATIC genes were corrected with YWHAZ and RPL4 genes. The muscular IMP content was determined by HPLC. The muscular IMP content in DPL was higher than that in LDPL and DLDPL, 25.00% (p 0.05) and 15.56% (p > 0.05), respectively. The muscular mRNA level of ADSL gene in DPL and LDPL was higher than that in DLDPL, 24.14% and 12.07%, respectively (p 0.05). The muscular mRNA level of ATIC gene in DPL and LDPL was higher than that in DLDPL, 66.67% and 33.33%, respectively (p 0.05). The muscular mRNA level of AMPD1 gene in DPL and LDPL was higher than that in DLDPL, 14.49% and 33.26%, respectively. Furthermore, the IMP content was positively correlated with the mRNA level of ADSL, AMPD1 and ATIC genes, respectively (p 0.05). The mRNA level of ADSL gene was highly related to that of AMPD1 and ATIC gene, respectively (p 0.01), while that of AMPD1 gene was not strongly correlated with that of ATIC gene (p > 0.05). The muscular mRNA level of AMPD1, ADSL and ATIC genes and the muscular IMP content in DPL were highest, followed by those in LDPL and DLDPL. The muscular IMP content was positively correlated with the muscular mRNA level of ADSL, AMPD1 and ATIC genes, respectively.
基金supported by the National Key R&D Program of China(Nos.2022YFA0806600,2022YFC3400700)the National Natural Science Foundation of China(Nos.22277093,22074110,21721005).
文摘Inosine is a vital RNA modification across three kingdoms of life.It has been demonstrated that inosine plays important roles in modulation of the fate of RNAs.In the current study,we developed a highly sensitive method to determine inosine in a single cell by N-cyclohexyl-N’-β-(4-methylmorpholinium)ethylcarbodiimide p-toluenesulfonate(CMCT)derivatization in combination with mass spectrometry analysis.The results showed that the detection sensitivity of inosine was increased by 556-fold after CMCT derivatization,with the limit of detection(LOD)being 4.5 amol.With the established method,we could detect inosine from 13.0 pg of total RNA of HEK293T cells.Meanwhile,inosine in RNA from a single cell could also be clearly detected due to the improved detection sensitivity.Moreover,we found the level of inosine in RNA of sleep-deprived mice was significantly increased compared to the control mice,indicating that inosine is associated with sleep behavior and might be a potential indicator of sleep disorder.Taken together,the chemical derivatization coupled with mass spectrometry analysis offers a valuable tool in determination of endogenous RNA modifications in a single cell,which should benefit the functional study of RNA modification in rare clinical samples.
基金supported by the National Natural Science Foundation of China(Nos.22074110,21635006,21721005)。
文摘6-Thioguanine(6TG)is a widely used chemotherapeutic agent for the treatment of a variety of human diseases including acute lymphoblastic leukemia.After entry into cells,6TG is metabolically converted into 6-thioguanosine(^(S)G)nucleotide that can be incorporated into the genome during DNA replication.^(S)G in genomic DNA could induce cell death by triggering the post-replicative mismatch repair(MMR)pathway.Meanwhile,incorporation of 6TG into the Cp G sites could perturb the global DNA methylation and gene regulation.However,the effect of 6TG on RNA modifications is still unknown.Adenosine-toinosine(A-to-I)editing in RNA is one of the most common post-transcriptional modifications in mammals and there is growing evidence showing the significant alteration of A-to-I RNA editing in tumor tissues compared to normal tissues.In the current study,we examined the incorporation of 6TG into RNA and investigated its effect on A-to-I editing of bladder cancer-associated protein(BLCAP)transcript in acute lymphoblastic leukemia cells.The results demonstrated that ^(S)G could be incorporated into various RNA species,with m RNA having the most abundant ^(S)G.In addition,the results showed 6TG treatment elevated A-to-I editing in BLCAP transcript through upregulating adenosine deaminase 2 acting on RNA(ADAR2),which eventually contributes to the decreased cell viability.This study highlights a new mechanism of the cytotoxicity of 6TG in inducing cell death.
文摘A 6-pyridinium salt(2)was obtalned from 2',3',5'-tri-O-acetyhnosine by use of phosphoryl chloride as the condensmg agent.The conversion of salt(2)into 6-(2- methylphenoxy)-purinenucleoside(3)denvatives under mild condition is also described.
基金Supported by National Natural Science Foundation of China(31501928)Youth Fund Project of Shandong Academy of Agricultural Sciences(2014QNM41)+1 种基金Science and Technology Development Program of Shandong Province(2015GNC111011)Natural Science Foundation of Shandong Province(ZR2015CM007)
文摘[ Objective] The paper was to investigate the degradation and deposition changes of inosine monophosphate （IMP） and its metabolites in muscle of lean pigs and crossbreeding pigs under cold storage condition at 4℃. [ Method] The contents of IMP and its metabolites in longissimus dorsi of lean pigs and crossbreeding pigs were determined by HPLC method. [ Result] Duroc, Landrace, Yorkshire and DLY pigs shared the same degradation and deposition pattern on IMP, inosine and hypoxanthine. On the second day of cold storage, the content of IMP reached the maximum value, which increased by 0.4% - 15.32% compared with the first day, and then it started to decline. On the fourth day of cold storage, the content of IMP significantly reduced by 23.81% - 39.06% than that on the second day. On the fifth and sixth day of cold storage, the content of IMP kept on falling down slowly and maintained around 1.0 mg/g. While the contents of inosine and hypoxanthine showed an increasing tendency with the extension of cold storage time. [ Conclusion ] Lean pigs Duroc, Landraee and Yorkshire and DLY three- way crossbreeding pigs shared the same degradation and deposition pattern on IMP and its metabolites. With the extension of cold storage, the content of IMP first increased then gradually decreased; while inosine and hypoxanthine gradually increased, and the difference among breeds was not significant.
基金supported by The National Natural Science Foundation of China(31972198,31622042)The National Key R&D Program of China(2016YFD0400803,2016YFD0401501).
文摘Inosine monophosphate(IMP),as a critical umami substance,is one of the most important indicators for evaluating the quality of meat products.Here,a sensitive electrochemiluminescence(ECL)biosensor based on graphdiyne(GDY)/AuNPs/luminol nanocomposites was constructed to detect IMP.The GDY/AuNPs/luminol nanocomposites were synthesized by using simple one-pot method.GDY utilized its 2D framework to disperse and fix gold nanoparticles,which inhibited the agglomeration of gold nanoparticles and greatly improved its stability and catalytic properties.Importantly,GDY/AuNPs/luminol nanocomposites showed excellent catalytic ability and superior ECL activity towards luminol-H_(2)O_(2) systems due to the synergistic effect of GDY and AuNPs.Under optimal conditions,the prepared biosensor exhibited a wide linear range from 0.01 g/L to 20 g/L,a satisfactory limit detection of 0.0013 g/L,as well as an excellent specificity.Moreover,we carried out the precise analysis of IMP in actual meat samples with acceptable results compared to the liquid chromatography.We believe that this work could offer an efficient ECL platform for accurate and reliable report of IMP levels,which is significant for maintaining food quality and safety.
基金the Natural Science Fund of Shandong Province, No.Y2001C04
文摘BACKGROUND: It has been demonstrated that adenosine can induce glial cell to release cytochrome C, enhance expression of apoptotic gene bax, inhibit anti-apoptotic gene bcl-2, and activate caspase-3 to apoptosis; Whereas inosine can inhibit neuronal apoptosis which is similar to bcl-2. OBJECTIVE: To observe the effects of inosine on neuronal apoptosis and expression of cytochrome C mRNA in rats after focal cerebral ischemia/reperfusion, and analyze the pathway of its neuroprotective effect. DESIGN: A randomised controlled animal trial. SETTINGS: Department of Neurology, Rongcheng Second People's Hospital; Department of Neurology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. MATERIALS: Sixty-eight rats, weighing 230-280 g and clean grade, were used. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and cytochrome C mRNA in situ hybridization kits and DAB staining kit were purchased from Wuhan Boster Biological Co., Ltd.; Inosine injection [200 mg (2 mL) each] from Qingdao First Pharmaceutical Factory. METHODS: The experiment was accomplished in the animal experimental center in Tongji Medical College of Huazhong University of Science and Technology from December 2003 to June 2005. ① Sixty-four rats were made into focal ischemia by middle cerebral artery occlusion (MCAO) with a nylon monofilament suture. The successfully induced rats were assigned to inosine group (n =32) and model group (n =32) at random. Rats in the inosine group were intraperitoneally administrated with inosine in dose of 100 mg/kg preoperatively, twice a day, 7 days in all. The rats in the control group were injected with the same dose of saline solution by the similar way preoperatively. Each group was randomized into ischemia /reperfusion 2, 6, 12, 24 hours, 2, 3, 7 and 14 days subgroups consisted of 4 rats. The other 4 rats were taken as the sham-operated group, the rats were given the same treatment except for not introduced the filament into the external carotid artery stump, and brain tissue was removed at 2 hours of reperfusion. ② In situ hybridization was performed to examine the expression of cytochrome C mRNA while TUNEL staining was made to characterize apoptosis. ③ The t test was used to compare the difference of measurement data. MAIN OUTCOME MEASURES: ① Neuronal apoptosis in the different regions of the ischemic brain tissue; ② Expression of cytochrome C mRNA in the different regions at different time points after MCAO. RESULTS: All the 68 rats were involved in the analysis of results. ① Neuronal apoptosis: A small number of TUNEL-positive cells were detected in the sham-operated brain and non-ischemic brain. The number of apoptotic cells in the ischemic cortex peaked at 24 hours of reperfusion [(72.00±1.98) cells] and that in the striatum peaked at 2 days [(94.75±3.57) cells], then decreased to the level of sham-operated group at 14 days. Inosine could reduce apoptotic cells from 12 hours to 7 days of reperfusion as compared with the model group (t =6.19-26.67, P < 0.01). ② Cytochrome C mRNA expression: There was weak expression of cytochrome C mRNA in both sham-operated brain and contralateral brain. Cytochrome C was detected at 2 hours of reperfusion in ischemic brain [(25.75±3.50), (39.75±2.49) cells], and strongly increased to a peak at 12 hours and 24 hours of reperfusion in cortex and striatum [(122.50±6.69), (119.25±5.12) cells], respectively. Furthermore, inosine could significantly decrease cytochrome C expression in cortex at 12 hours to 14 days of reperfusion after ischemic reperfusion and that in striatum at 12 hours to 3 days (t =8.67-43.26, P < 0.01). CONCLUSION: Inosine can exert a neuroprotective effect by inhibiting apoptosis and cytochrome C mRNA expression.
文摘The adsorption characteristics of inosine from fermentation solution on anion exchange resin under the condition of different PH, resin type are investigated. Besides 3 the desorption conditions are studied under different temperature.The adsorption and desorption mechanism are described to obtain the optimumtechnological condition of inosine extraction.
文摘This is a correction to:Hao Cheng,Jun Yu,Chi Chun Wong,Adenosine-to-inosine RNA editing in cancer:molecular mechanisms and downstream targets,Protein&Cell,2024;https://doi.org/10.1093/procel/pwae039 In the originally published version of the manuscript there were errors in Figure 2.In panel H,text should read:"Loses capacity"instead of:"oses capacity";a redundant letter"I"that was highlighted should be removed.
基金funded by the National Natural Science Foundation of China(Grant No.32202485)the Fund for Distinguished Young Scholars from Henan Academy of Agricultural Sciences(Grant No.2024JQ02)+1 种基金the Zhongyuan Sci-Tech Innovation Leading Talents(Grant No.244200510041)the Key SciTech R&D Project of Joint Foundation in Henan Province(Grant No.232301420024).
文摘Purines are building blocks for DNA and RNA,found as the energy currency of cells(ATP and GTP),used as signaling molecules(cGMP,cAMP and ATP),and served as precursors for synthesizing primary products such as polysaccharides,sucrose,and phospholipids as well as secondary products(Stasolla et al.,2003;Pareek et al.,2020).Thus,the synthesis of purines is a critical pathway in the cells of all living organisms.Purines can be synthesized through two pathways:de novo and salvage(Stasolla et al.,2003).Recent investigations revealed that purine synthesis is vital for the proper development of chloroplasts in plants.In Arabidopsis,CIA1 encodes the enzyme glutamine phosphoribosyl pyrophosphate amidotransferase,which catalyzes the first committed step of purine de novo biosynthesis,the loss-of-function mutant cia1 shows small,pale-green mosaic leaves(Hung et al.,2004).In rice,both VAL1 and GARS encode glycinamide ribonucleotide synthetase that mediates the second step in purine biosynthesis.
文摘RNA contains diverse post-transcriptional modifications,and its catabolic breakdown yields numerous modified nucleosides requiring correct processing,but the mechanisms remain unknown.Here,we demonstrate that three RNA-derived modified adenosines,N6-methyladenosine(m6A),N6,N6-dimethyladenosine(m6,6A),and N6-isopentenyladenosine(i6A),are sequentially metabolized into inosine monophosphate(IMP)to mitigate their intrinsic cytotoxicity.
基金funded through the German Cancer Aid(Max-Eder program)funded through the Deutsche Forschungsgemeinschaft(DFG)Cluster of Excellence:EXC 2124 Controlling Microbes to Fight Infections(CMFI)+4 种基金Excellence iFIT(EXC 2180)the ERC starting grant SOAR.funded by Deutsche Forschungsgemeinschaft(DFG)Cluster of Excellence iFIT EXC2180DFG grant SE2234/3-2the Hector Foundation MINT Personal Fonds.
文摘In a recent publication in Cell,Stevens et al.uncovered that microbiota disruptions reduced inosine levels and impaired CD8^(+)T cell immunity against influenza infection in early life.Treatment with inosine-producing bacteria or inosine alone restored T cell responsiveness through a nuclear factor interleukin 3(NFIL3)-dependent mechanism.
基金Supported by University of Zurich:"URPP:Translational Cancer research"the"MERIT"project supported by the FP7 European Union’s ResearchInnovation Funding program
文摘The functional impact of modifications of cellular RNAs,including m RNAs,mi RNAs and lnc RNAs,is a field of intense study.The role of such modifications in cancer has started to be elucidated.Diverse and sometimes opposite effects of RNA modifications have been reported.Some RNA modifications promote,while ot-hers decrease the growth and invasiveness of cancer.The present manuscript reviews the current knowledge on the potential impacts of N6-Methyladenosine,Pse-udouridine,Inosine,2’O-methylation or methylcytidine in cancer’s RNA.It also highlights the remaining qu-estions and provides hints on research avenues and potential therapeutic applications,whereby modulating dynamic RNA modifications may be a new method to treat cancer.
基金supported by the National Natural Science Foundation of China (Nos.81925037, 82073976, and 31700013)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (No.2017BT01Y036)+2 种基金Guangdong Natural Science Funds for Distinguished Young Scholar(No.2021B1515020065)the Young Elite Scientists Sponsorship Program by the China Association of Chinese Medicine (No.QNRC2-B06)the Dongguan Academician Workstation Project (No.DGYSZ-2018-03)。
文摘An eco-friendly and fast HPLC method was developed for the determination of adenosine, inosine, guanosine and uridine in Cordyceps and related products(fermented mycelia of Hirsutella sinensis and Paecilomyces hepiali). The sample was ultrasonically extracted using 0.5% phosphoric acid solutions for 2.5 min. Sample separation was performed on a Poroshell SB-Aq column(50 mm × 4.6 mm, 2.7 μm) using eco-friendly mobile phase consisting of formic acid and ammonium formate aqueous solution at a flow rate of 1.0 m L·min;. The detection wavelength was 260 nm. The developed HPLC method showed good linearity with correlation coefficients of 1.0000 in the test range. Good precision, repeatability and stability of this method were also observed(RSD ≤ 2.81%).The recovery ranged from 91.84%-105.19%(RSD ≤ 2.59%). Compared with reported methods, the current method did not use harmful organic solvent and took only 10.5 min. It obtained a high eco-score of 91 by the "Analytical Eco-Scale" tool. The developed method is eco-friendly and fast, which is suitable for the quality evaluation of Cordyceps and related products.
基金the National Natural Science Foundation of China(32072182).
文摘Hyperuricemia is a critical threat to human health,and a high inosine diet can increase the prevalence of it.Lacticaseibacillus rhamnosus Fmb14 was isolated from traditional fermented Chinese yogurt,and its inosine degradation rate reached 36.3%at 109 CFU/mL for 24 h.LC-MS analysis revealed that high concentrations of inosine could activate compensatory metabolic pathways of L.rhamnosus Fmb14 to catalyse inosine as an energy source and produce intracellular folic acid and riboflavin.The contents of folic acid and riboflavin were 6.0 and 4.3 fold increased after inosine treatment in the cell-free extracts(CFE).L.rhamnosus Fmb14 CFE treatment ameliorates hyperuricemia through xanthine oxidase(XOD)inhibition and ATP-binding cassette subfamily G member 2(ABCG2)promotion,both of which are responsible for uric acid(UA)synthesis and secretion in HepG2 and Caco2 cells,respectively.The in vivo results showed that the serum UA level decreased from 236.28 to 149.28μmol/L after 8 weeks of oral administration of L.rhamnosus Fmb14 in inosine-induced hyperuricemia model mice.Our results revealed that L.rhamnosus Fmb14 has a potential as a biological therapeutic agent in hyperuricemia prevention.
