目的:探讨PCR技术在绿脓杆菌感染肺炎大鼠模型中进行检测的方法可行性以及大鼠体内IL23的表达水平变化。方法:将健康SD大鼠随机分为3组,空白对照组、实验对照组和肺炎感染组。在绿脓杆菌肺炎模型建立后,设计绿脓杆菌的特异性引物,进行3...目的:探讨PCR技术在绿脓杆菌感染肺炎大鼠模型中进行检测的方法可行性以及大鼠体内IL23的表达水平变化。方法:将健康SD大鼠随机分为3组,空白对照组、实验对照组和肺炎感染组。在绿脓杆菌肺炎模型建立后,设计绿脓杆菌的特异性引物,进行3组大鼠体内绿脓杆菌感染的PCR鉴定,并用qPCR和ELISA技术检测大鼠体内IL23水平变化。结果:①PCR技术检测到肺炎大鼠模型中的绿脓杆菌,其中肺组织检出率为100%,而对照组的PCR结果是阴性。②绿脓杆菌感染肺炎大鼠模型建立后,大鼠的IL23 m RNA逐渐上升,在第3天达到最高值,相比对照组,有显著差异(分别是60852.9±1474.2和1987.7±246.4拷贝,P<0.05);血清中的IL23蛋白水平也逐渐上升,在第1周到达最高值,相比对照组,有显著差异(分别是297.4±14.7和123.8±18.3pg/m L,P<0.05)。结论:本研究建立了大鼠体内的高特异性、快速、简便绿脓杆菌感染检测PCR方法,发现大鼠IL23在绿脓杆菌感染后显著升高,在绿脓杆菌肺炎和IL23之间建立了联系。展开更多
AIM: To assess whether the polymorphisms of NOD2/ CARD15 , autophagy-related 16-like 1 (ATG16L1 ), and interleukin-23 receptor (IL23R ) genes play a more critical role in the susceptibility of childhood-onset than in ...AIM: To assess whether the polymorphisms of NOD2/ CARD15 , autophagy-related 16-like 1 (ATG16L1 ), and interleukin-23 receptor (IL23R ) genes play a more critical role in the susceptibility of childhood-onset than in adult-onset Crohn’s disease (CD). METHODS: Polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 ; rs2241880 A/G of ATG16L1 , and rs11209026 (R381Q) of IL23R gene were assessed in 110 childhood-onset CD, 364 adult-onset CD, and 539 healthy individuals. Analysis of polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 genotyping was performed by allele specific polymerase chain reaction (PCR) or by PCR-restriction fragment length polymor-phism analysis. The polymorphisms rs2241880 A/G of the ATG16L1 , and rs11209026 (R381Q) of the IL23R gene in the children’s cohort were genotyped by PCR and melting curve analysis whereas adult group genotyping was performed using the Affymetrix Genome-Wide Human SNP Array 5.0 (500K). RESULTS: The 3020insC allele in NOD2/CARD15 was significantly higher in childhood than in adult-onset CD (P = 0.0067). Association with at least 1 NOD2/CARD15 variant was specific for ileal disease (with or without co- lonic involvement). Even if the frequency of G allele of the rs2241880 ATG16L1 polymorphism was increased in both paediatric and adult CD patients compared to con- trols (P = 0.017 and P = 0.001, respectively), no difference was observed between the childhood and the adult cohort. The rare Q allele of IL23R rs11209026 polymorphism was underrepresented in both paediatric and adult CD cases (P = 0.0018 and P = 0.04, respectively) and no difference was observed between the childhood and the adult cohort. The presence of the rs2241880 ATG16L1 and rs11209026 IL23R polymorphisms did not influence disease phenotype. CONCLUSION: Polymorphism 3020insC in NOD2/ CARD15 occurs statistically significantly more often in patients with childhood-onset CD than in patients with adult-onset CD. The ATG16L1 and IL23R variants are associated with susceptibility to CD, but not earlyonset disease.展开更多
Inflammatory bowel disease is a group of diseases that includes Crohn＇s disease （CD） and ulcerative colitis. CD is characterized as a chronic inflammatory disease of the gastrointestinal tract, ranging from the mou...Inflammatory bowel disease is a group of diseases that includes Crohn＇s disease （CD） and ulcerative colitis. CD is characterized as a chronic inflammatory disease of the gastrointestinal tract, ranging from the mouth to the anus. Although there are gross pathological and histological similarities between CD and Johne＇s dis- ease of cattle, the cause of CD remains controversial. It is vital to understand fully the cause of this disease because it affects approximately 500 000 people in North America and Europe. It ranges from 27 to 48 cases per 100 000 people. There are many theories on the cause of CD ranging from possible association with environmental factors including microorganisms to imbalance in the intestinal normal flora of the pa- tients. Regardless of the environmental trigger, there is strong evidence that a genetic disposition is a major key in acquiring CD. Many studies have proven the link between mutations in the ATG16L, NOD2/CARD15, IBDS, CTLA4, TNFSF15 and IL23R genes, and CD. The purpose of this review is to examine all genetic aspects and theories of CD, including up to date multiple popu- lation studies performed worldwide.展开更多
AIM To investigate the association of seven single nucleotide polymorphisms(SNPs)of the IL23 R gene with the clinical picture of ulcerative colitis(UC).METHODS Genomic DNA samples of 131 patients(66 males,65 females,m...AIM To investigate the association of seven single nucleotide polymorphisms(SNPs)of the IL23 R gene with the clinical picture of ulcerative colitis(UC).METHODS Genomic DNA samples of 131 patients(66 males,65 females,mean age 55.4±15.8 years)with Caucasian origin,diagnosed with UC were investigated.The diagnosis of UC was based on the established clinical,endoscopic,radiological,and histopathological guidelines.DNA was extracted from peripheral blood leukocytes by routine salting out method.Polymerase chain reaction and restriction fragment length polymorphism were used to identify the alleles of seven SNPs of IL23 R gene(rs11209026,rs10889677,rs1004819,rs2201841,rs7517847,rs10489629,rs7530511).RESULTS Four out of seven analyzed SNPs had statistically significant influence on the clinical picture of UC.Two SNPs were associated with greater colonic extension(rs2201841 P=0.0084;rs10489629 P=0.0405).For two of the SNPs,there was more frequently need for operations(rs2201841 P=0.0348,OR=8.0;rs10889677 P=0.0347,OR=8.0).The rs2201841 showed to be a risk factor for the development of iron deficiency(P=0.0388,OR=6.1837).For patients with the rs10889677,a therapy with azathioprine was more frequently necessary(P=0.0116,OR=6.1707).Patients with rs10489629 SNP had a lower risk for weight loss(P=0.0169,OR=0.3394).Carriers of the heterozygous variant had a higher risk for an extended disease(P=0.0284).The rs7517847 showed a protective character leading to mild bowel movements.Three SNPs demonstrated no statistically significant influence on any examined clinical features of UC.CONCLUSION We demonstrated susceptible or protective character of the investigated IL23 R SNPs on the phenotype of UC,confirming the genetic association.展开更多
AIM:To investigate the frequency of NOD2, IL23R and ATG16L1 genetic variants in a case-control panel for inflammatory bowel disease (IBD) from Lithuania.METHODS: One hundred and eighty unrelated IBD pa- tients [57 Cro...AIM:To investigate the frequency of NOD2, IL23R and ATG16L1 genetic variants in a case-control panel for inflammatory bowel disease (IBD) from Lithuania.METHODS: One hundred and eighty unrelated IBD pa- tients [57 Crohn's disease (CD) and 123 ulcerative colitis (UC)] and 186 healthy controls were genotyped for the following known genetic susceptibility variants:NOD2-Arg702Trp (rs2066844), Gly908Arg (rs2066845) and Leu1007insC (rs2066847), as well as IL23R-Arg381Gln (rs11209026) and ATG16L1-Thr300Ala (rs2241880).RESULTS:The effect that carriership of at least one NOD2 risk allele predisposes to CD was replicated in the Lithuanian population (41.1% CD vs 16.9% controls, P=2×10-4, OR=3.48,95% CI:1.81-6.72). In the allelic single marker analysis, Leu1007insC was strongly associated with CD (21.4% CD vs 4.7% controls, P=3.687×10-8, OR=5.54, 95% CI:2.85-10.75). Neither the other two NOD2 variants, nor the known variants in IL23R and ATG16L1 were found to be risk factors for CD, UC or IBD. However, our relatively small study population was underpowered to demonstrate such weak to moderate disease associations.CONCLUSION: The results support a strong association between CD susceptibility and the Leu1007insC variant in NOD2 in the Lithuanian study population.展开更多
BACKGROUND The lethal-7(let-7)family members and their targets are involved in the development and progression of tumors.Let-7-related polymorphisms have been reported to be associated with tumorigenesis and prognosis...BACKGROUND The lethal-7(let-7)family members and their targets are involved in the development and progression of tumors.Let-7-related polymorphisms have been reported to be associated with tumorigenesis and prognosis.In gastric cancer,however,the related studies are limited.AIM To investigate the role of let-7-related microRNA polymorphisms in the tumorigenesis and prognosis of gastric cancer in a Chinese population.METHODS A total of 898 gastric cancer patients and 992 tumor-free controls were recruited into this study from 2008 to 2013.Gastric cancer patients were followed periodically.Ten single nucleotide polymorphisms(SNPs)in the let-7 gene region or their target mRNAs were genotyped using the MassARRAY system and their associations with the risk for or overall survival of gastric cancer were analyzed.RESULTS All the ten SNPs were in Hardy-Weinberg equilibrium.The C allele of the rs3811463 polymorphism in the 3’-untranslated region(UTR)of LIN28A was associated with a lower risk of gastric cancer[odds ratio(OR)=0.74,95%confidence interval(CI):0.61-0.88,P=0.001]after adjustment for age and Helicobacter pylori status.Seven hundred and thirty-five gastric cancer patients who had undergone radical tumorectomy were included in the survival analysis and their 5-year survival rate was 53.9%(95%CI:50.1%-57.6%).The rs10889677 in the 3’-UTR of IL23R was corresponded to the prognosis of gastric cancer in a dose-response manner,in which the death risk increased by 25%[hazard ratio(HR)=1.25,95%CI:1.04-1.45,P=0.011]with each increase in the number of C alleles after controlling for other potential clinicopathological parameters.CONCLUSION The let-7-related polymorphism rs3811463 in LIN28A is associated with the susceptibility to gastric cancer and the let-7-related polymorphism rs10889677 in IL23R is associated with the prognosis of gastric cancer.展开更多
文摘目的:探讨PCR技术在绿脓杆菌感染肺炎大鼠模型中进行检测的方法可行性以及大鼠体内IL23的表达水平变化。方法:将健康SD大鼠随机分为3组,空白对照组、实验对照组和肺炎感染组。在绿脓杆菌肺炎模型建立后,设计绿脓杆菌的特异性引物,进行3组大鼠体内绿脓杆菌感染的PCR鉴定,并用qPCR和ELISA技术检测大鼠体内IL23水平变化。结果:①PCR技术检测到肺炎大鼠模型中的绿脓杆菌,其中肺组织检出率为100%,而对照组的PCR结果是阴性。②绿脓杆菌感染肺炎大鼠模型建立后,大鼠的IL23 m RNA逐渐上升,在第3天达到最高值,相比对照组,有显著差异(分别是60852.9±1474.2和1987.7±246.4拷贝,P<0.05);血清中的IL23蛋白水平也逐渐上升,在第1周到达最高值,相比对照组,有显著差异(分别是297.4±14.7和123.8±18.3pg/m L,P<0.05)。结论:本研究建立了大鼠体内的高特异性、快速、简便绿脓杆菌感染检测PCR方法,发现大鼠IL23在绿脓杆菌感染后显著升高,在绿脓杆菌肺炎和IL23之间建立了联系。
文摘AIM: To assess whether the polymorphisms of NOD2/ CARD15 , autophagy-related 16-like 1 (ATG16L1 ), and interleukin-23 receptor (IL23R ) genes play a more critical role in the susceptibility of childhood-onset than in adult-onset Crohn’s disease (CD). METHODS: Polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 ; rs2241880 A/G of ATG16L1 , and rs11209026 (R381Q) of IL23R gene were assessed in 110 childhood-onset CD, 364 adult-onset CD, and 539 healthy individuals. Analysis of polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 genotyping was performed by allele specific polymerase chain reaction (PCR) or by PCR-restriction fragment length polymor-phism analysis. The polymorphisms rs2241880 A/G of the ATG16L1 , and rs11209026 (R381Q) of the IL23R gene in the children’s cohort were genotyped by PCR and melting curve analysis whereas adult group genotyping was performed using the Affymetrix Genome-Wide Human SNP Array 5.0 (500K). RESULTS: The 3020insC allele in NOD2/CARD15 was significantly higher in childhood than in adult-onset CD (P = 0.0067). Association with at least 1 NOD2/CARD15 variant was specific for ileal disease (with or without co- lonic involvement). Even if the frequency of G allele of the rs2241880 ATG16L1 polymorphism was increased in both paediatric and adult CD patients compared to con- trols (P = 0.017 and P = 0.001, respectively), no difference was observed between the childhood and the adult cohort. The rare Q allele of IL23R rs11209026 polymorphism was underrepresented in both paediatric and adult CD cases (P = 0.0018 and P = 0.04, respectively) and no difference was observed between the childhood and the adult cohort. The presence of the rs2241880 ATG16L1 and rs11209026 IL23R polymorphisms did not influence disease phenotype. CONCLUSION: Polymorphism 3020insC in NOD2/ CARD15 occurs statistically significantly more often in patients with childhood-onset CD than in patients with adult-onset CD. The ATG16L1 and IL23R variants are associated with susceptibility to CD, but not earlyonset disease.
基金Supported by The Broad Foundation grant,No. IBD-0207R
文摘Inflammatory bowel disease is a group of diseases that includes Crohn＇s disease （CD） and ulcerative colitis. CD is characterized as a chronic inflammatory disease of the gastrointestinal tract, ranging from the mouth to the anus. Although there are gross pathological and histological similarities between CD and Johne＇s dis- ease of cattle, the cause of CD remains controversial. It is vital to understand fully the cause of this disease because it affects approximately 500 000 people in North America and Europe. It ranges from 27 to 48 cases per 100 000 people. There are many theories on the cause of CD ranging from possible association with environmental factors including microorganisms to imbalance in the intestinal normal flora of the pa- tients. Regardless of the environmental trigger, there is strong evidence that a genetic disposition is a major key in acquiring CD. Many studies have proven the link between mutations in the ATG16L, NOD2/CARD15, IBDS, CTLA4, TNFSF15 and IL23R genes, and CD. The purpose of this review is to examine all genetic aspects and theories of CD, including up to date multiple popu- lation studies performed worldwide.
基金Supportedby Hungarian Science Foundation(OTKA),No.K103983 and No.K119540
文摘AIM To investigate the association of seven single nucleotide polymorphisms(SNPs)of the IL23 R gene with the clinical picture of ulcerative colitis(UC).METHODS Genomic DNA samples of 131 patients(66 males,65 females,mean age 55.4±15.8 years)with Caucasian origin,diagnosed with UC were investigated.The diagnosis of UC was based on the established clinical,endoscopic,radiological,and histopathological guidelines.DNA was extracted from peripheral blood leukocytes by routine salting out method.Polymerase chain reaction and restriction fragment length polymorphism were used to identify the alleles of seven SNPs of IL23 R gene(rs11209026,rs10889677,rs1004819,rs2201841,rs7517847,rs10489629,rs7530511).RESULTS Four out of seven analyzed SNPs had statistically significant influence on the clinical picture of UC.Two SNPs were associated with greater colonic extension(rs2201841 P=0.0084;rs10489629 P=0.0405).For two of the SNPs,there was more frequently need for operations(rs2201841 P=0.0348,OR=8.0;rs10889677 P=0.0347,OR=8.0).The rs2201841 showed to be a risk factor for the development of iron deficiency(P=0.0388,OR=6.1837).For patients with the rs10889677,a therapy with azathioprine was more frequently necessary(P=0.0116,OR=6.1707).Patients with rs10489629 SNP had a lower risk for weight loss(P=0.0169,OR=0.3394).Carriers of the heterozygous variant had a higher risk for an extended disease(P=0.0284).The rs7517847 showed a protective character leading to mild bowel movements.Three SNPs demonstrated no statistically significant influence on any examined clinical features of UC.CONCLUSION We demonstrated susceptible or protective character of the investigated IL23 R SNPs on the phenotype of UC,confirming the genetic association.
基金Supported by The German Ministry of Education and Research through the National Genome Research Network
文摘AIM:To investigate the frequency of NOD2, IL23R and ATG16L1 genetic variants in a case-control panel for inflammatory bowel disease (IBD) from Lithuania.METHODS: One hundred and eighty unrelated IBD pa- tients [57 Crohn's disease (CD) and 123 ulcerative colitis (UC)] and 186 healthy controls were genotyped for the following known genetic susceptibility variants:NOD2-Arg702Trp (rs2066844), Gly908Arg (rs2066845) and Leu1007insC (rs2066847), as well as IL23R-Arg381Gln (rs11209026) and ATG16L1-Thr300Ala (rs2241880).RESULTS:The effect that carriership of at least one NOD2 risk allele predisposes to CD was replicated in the Lithuanian population (41.1% CD vs 16.9% controls, P=2×10-4, OR=3.48,95% CI:1.81-6.72). In the allelic single marker analysis, Leu1007insC was strongly associated with CD (21.4% CD vs 4.7% controls, P=3.687×10-8, OR=5.54, 95% CI:2.85-10.75). Neither the other two NOD2 variants, nor the known variants in IL23R and ATG16L1 were found to be risk factors for CD, UC or IBD. However, our relatively small study population was underpowered to demonstrate such weak to moderate disease associations.CONCLUSION: The results support a strong association between CD susceptibility and the Leu1007insC variant in NOD2 in the Lithuanian study population.
基金Supported by National Natural Science Foundation of China,No.81703293,81673145,and No.81373084the Research Program of the Education Department of Jilin Province,No.2016487the Scientific and Technological Development Program of Jilin Province,No.20180414055GH
文摘BACKGROUND The lethal-7(let-7)family members and their targets are involved in the development and progression of tumors.Let-7-related polymorphisms have been reported to be associated with tumorigenesis and prognosis.In gastric cancer,however,the related studies are limited.AIM To investigate the role of let-7-related microRNA polymorphisms in the tumorigenesis and prognosis of gastric cancer in a Chinese population.METHODS A total of 898 gastric cancer patients and 992 tumor-free controls were recruited into this study from 2008 to 2013.Gastric cancer patients were followed periodically.Ten single nucleotide polymorphisms(SNPs)in the let-7 gene region or their target mRNAs were genotyped using the MassARRAY system and their associations with the risk for or overall survival of gastric cancer were analyzed.RESULTS All the ten SNPs were in Hardy-Weinberg equilibrium.The C allele of the rs3811463 polymorphism in the 3’-untranslated region(UTR)of LIN28A was associated with a lower risk of gastric cancer[odds ratio(OR)=0.74,95%confidence interval(CI):0.61-0.88,P=0.001]after adjustment for age and Helicobacter pylori status.Seven hundred and thirty-five gastric cancer patients who had undergone radical tumorectomy were included in the survival analysis and their 5-year survival rate was 53.9%(95%CI:50.1%-57.6%).The rs10889677 in the 3’-UTR of IL23R was corresponded to the prognosis of gastric cancer in a dose-response manner,in which the death risk increased by 25%[hazard ratio(HR)=1.25,95%CI:1.04-1.45,P=0.011]with each increase in the number of C alleles after controlling for other potential clinicopathological parameters.CONCLUSION The let-7-related polymorphism rs3811463 in LIN28A is associated with the susceptibility to gastric cancer and the let-7-related polymorphism rs10889677 in IL23R is associated with the prognosis of gastric cancer.
