AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines ...AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.展开更多
BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediat...BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes(T1D).While it has been established that 20%-30%of T1D patients suffer from autoimmune thyroid disease(AITD),there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients.Among commercially available anti-islet autoantibodies,glutamic acid decarboxylase 65 autoantibodies(GADAs)are often the first marker measured in general clinical practice.AIM To investigate the frequency of anti-islet autoantibodies in AITD patients.METHODS Our study involved four hundred ninety-five AITD patients,categorized into three distinct groups:AITD with T1D(n=18),AITD with phenotypic type 2 diabetes(T2D)(n=81),and AITD without diabetes(n=396),and the enzyme-linked immunosorbent assay(ELISA)was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody(3 Screen ICA),GADA,insulinoma-associated antigen-2 autoantibodies(IA-2As),and zinc transporter 8 autoantibodies(ZnT8As)within these groups.RESULTS The frequency of 3 Screen ICA in AITD patients with T1D,T2D,and those without diabetes were 88.9%,6.2%,and 5.1%,respectively,with no significant difference seen between the latter two groups.Notably,the frequency of 3 Screen ICA was 11.1%higher in AITD patients with T1D,1.3%higher in AITD patients with T2D,and 1.1%higher in AITD patients without diabetes compared to GADA,respectively.Furthermore,12.5%,20.0%,and 20.0%of the 3 Screen ICA-positive patients were negative for GADA.Additionally,1.3%of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies.Among the 3 Screen ICA-positive patients,there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes(37.5%vs 5.0%,P<0展开更多
Background:Egg production is economically important in the meat-type chicken industry.To better understand the molecular genetic mechanism of egg production in meat-type chicken,genetic parameter estimation,genome-wid...Background:Egg production is economically important in the meat-type chicken industry.To better understand the molecular genetic mechanism of egg production in meat-type chicken,genetic parameter estimation,genome-wide association analyses combined with meta-analyses,Bayesian analyses,and selective sweep analyses were performed to screen single nucleotide polymorphisms(SNPs)and other genetic loci that were significantly associated with egg number traits in 11,279 chickens from seven material lines.Results:Yellow-feathered meat-type chickens laid 115 eggs at 43 weeks of age and white-feathered chickens laid 143 eggs at 60 weeks of age,with heritability ranging from 0.034–0.258.Based on meta-analyses and selective sweep analyses,one region(10.81–13.05 Mb)on chromosome Z was associated with egg number in all lines.Further analyses using the W2 line was also associated with the same region,and 29 SNPs were identified that significantly affected estimation of breeding value of egg numbers.The 29 SNPs were identified as having a significant effect on the egg number EBV in 3194 birds in line W2.There are 36 genes in the region,with glial cell derived neurotrophic factor,DAB adaptor protein 2,protein kinase AMP-activated catalytic subunit alpha 1,NAD kinase 2,mitochondrial,WD repeat domain 70,leukemia inhibitory factor receptor alpha,complement C6,and complement C7 identified as being potentially affecting to egg number.In addition,three SNPs(rs318154184,rs13769886,and rs313325646)associated with egg number were located on or near the prolactin receptor gene.Conclusion:Our study used genomic information from different chicken lines and populations to identify a genomic region(spanning 2.24 Mb)associated with egg number.Nine genes and 29 SNPs were identified as the most likely candidate genes and variations for egg production.These results contribute to the identification of candidate genes and variants for egg traits in poultry.展开更多
基金Project supported by the National Natural Science Foundation of China,No.39770861.and JANSSEN Science Research Foundation.
文摘AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.
文摘BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes(T1D).While it has been established that 20%-30%of T1D patients suffer from autoimmune thyroid disease(AITD),there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients.Among commercially available anti-islet autoantibodies,glutamic acid decarboxylase 65 autoantibodies(GADAs)are often the first marker measured in general clinical practice.AIM To investigate the frequency of anti-islet autoantibodies in AITD patients.METHODS Our study involved four hundred ninety-five AITD patients,categorized into three distinct groups:AITD with T1D(n=18),AITD with phenotypic type 2 diabetes(T2D)(n=81),and AITD without diabetes(n=396),and the enzyme-linked immunosorbent assay(ELISA)was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody(3 Screen ICA),GADA,insulinoma-associated antigen-2 autoantibodies(IA-2As),and zinc transporter 8 autoantibodies(ZnT8As)within these groups.RESULTS The frequency of 3 Screen ICA in AITD patients with T1D,T2D,and those without diabetes were 88.9%,6.2%,and 5.1%,respectively,with no significant difference seen between the latter two groups.Notably,the frequency of 3 Screen ICA was 11.1%higher in AITD patients with T1D,1.3%higher in AITD patients with T2D,and 1.1%higher in AITD patients without diabetes compared to GADA,respectively.Furthermore,12.5%,20.0%,and 20.0%of the 3 Screen ICA-positive patients were negative for GADA.Additionally,1.3%of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies.Among the 3 Screen ICA-positive patients,there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes(37.5%vs 5.0%,P<0
基金the Guangdong Provincial Key Research and Development Program(2020B02022002)the Shandong Agricultural Seed Improvement Project(2020LZGC013)the Technological Innovation Project of Chinese Academy of Agricultural Sciences(CAAS-ZDRW202005)。
文摘Background:Egg production is economically important in the meat-type chicken industry.To better understand the molecular genetic mechanism of egg production in meat-type chicken,genetic parameter estimation,genome-wide association analyses combined with meta-analyses,Bayesian analyses,and selective sweep analyses were performed to screen single nucleotide polymorphisms(SNPs)and other genetic loci that were significantly associated with egg number traits in 11,279 chickens from seven material lines.Results:Yellow-feathered meat-type chickens laid 115 eggs at 43 weeks of age and white-feathered chickens laid 143 eggs at 60 weeks of age,with heritability ranging from 0.034–0.258.Based on meta-analyses and selective sweep analyses,one region(10.81–13.05 Mb)on chromosome Z was associated with egg number in all lines.Further analyses using the W2 line was also associated with the same region,and 29 SNPs were identified that significantly affected estimation of breeding value of egg numbers.The 29 SNPs were identified as having a significant effect on the egg number EBV in 3194 birds in line W2.There are 36 genes in the region,with glial cell derived neurotrophic factor,DAB adaptor protein 2,protein kinase AMP-activated catalytic subunit alpha 1,NAD kinase 2,mitochondrial,WD repeat domain 70,leukemia inhibitory factor receptor alpha,complement C6,and complement C7 identified as being potentially affecting to egg number.In addition,three SNPs(rs318154184,rs13769886,and rs313325646)associated with egg number were located on or near the prolactin receptor gene.Conclusion:Our study used genomic information from different chicken lines and populations to identify a genomic region(spanning 2.24 Mb)associated with egg number.Nine genes and 29 SNPs were identified as the most likely candidate genes and variations for egg production.These results contribute to the identification of candidate genes and variants for egg traits in poultry.
