AIM: To characterize gene polymorphism of several cytokine gene in-patients with AIH and PBC and to analyze the difference of the polymorphism distribution between Chinese patients and healthy controls.METHODS: The st...AIM: To characterize gene polymorphism of several cytokine gene in-patients with AIH and PBC and to analyze the difference of the polymorphism distribution between Chinese patients and healthy controls.METHODS: The study population consisted of 62 patients with AIH, and 77 patients with PBC. The genetic profile of four cytokines was analyzed by restriction fragmentlength polymorphism after specific PCR amplification (PCR-RFLP) or sequence-specific primers PCR (SSP-PCR). The analyzed gene polymorphism included interleukin-1 (IL-1) (at position +3 953 and IL-1RN intron 2), IL-6 (atposition -174), IL-10 promoter (at position -1 082, -819, and -592). The control group consisted of 160 healthyblood donors.RESULTS: The majority of Chinese people including patients and healthy controls exhibited IL-1B 1,1genotype, and there was no significant difference in AIH, PBC patients and controls. There were highly statistically significant differences in the distribution of the IL-1RN gene polymorphism between the patients with PBCcompared with controls. The frequency of IL-1RN 1,1was significantly higher (90.9% vs 79.4%, P = 0.03)and the frequency of IL-1RN 1,2 was significantly lower in PBC patients (6.5% vs 17.5%, P = 0.01). No statistical difference was observed between AIH patients and controls. All of the 160 healthy controls and 62 cases of AIH patients exhibited IL-6-174GG genotype, and there were four cases, which expressed IL-6-174GC genotype in 77 cases of PBC patients. The frequency of IL-6-174GC was markedly significantly higher in PBC patients compared with controls (5.2% vs 0%, P = 0.004). No statistically significant difference was found in the distribution of IL-10 promoter genotype in AIH and PBC patients compared with controls. CONCLUSION: The polymorphisms of IL-1RN and IL-6 -174G/C appear to be associated with PBC in Chinese patients.展开更多
Vitamin D is a seco-steroid involved in calcium and phosphorus metabolism,and bone formation and mineralization, through binding to a specific nuclear receptor,vitamin D receptor（VDR）.Besides its well-established fu...Vitamin D is a seco-steroid involved in calcium and phosphorus metabolism,and bone formation and mineralization, through binding to a specific nuclear receptor,vitamin D receptor（VDR）.Besides its well-established functions on bone health,multiple lines of evidence have indicated the immunomodulatory roles of vitamin D.Vitamin D can affect both innate and adaptive immunity,and prevent autoimmune responses efficiently.Vitamin D regulates the immune responses by suppressing T cell proliferation and modulating macrophage functions.Epidemiological studies have shown that vitamin D deficiency is associated with multiple diseases such as rickets and cancer.Moreover,associations between vitamin D and autoimmune diseases have been confirmed in multiple sclerosis（MS）,rheumatoid arthritis（RA）,etc.The present review mainly summarized the recent findings on the immunomodulatory role of vitamin D in various disorders,with special focus on its role in MS,an autoimmune disease of the nervous system.展开更多
Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and th...Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and there are currently no effective treatments. The development of neural stem cell(NSC) transplantation provides a promising strategy to treat neurodegenerative disease. However, the limited availability of NSCs prevents their application in neural disease therapy. In this study, we generated NSCs from induced pluripotent stem cells(iPSCs) and transplanted these cells into mice with experimental autoimmune encephalomyelitis(EAE), a model of MS. The results showed that transplantation of iPSC-derived NSCs dramatically reduced T cell infiltration and ameliorated white matter damage in the treated EAE mice. Correspondingly, the disease symptom score was greatly decreased, and motor ability was dramatically rescued in the iPSC-NSC-treated EAE mice, indicating the effectiveness of using iPSC-NSCs to treat MS. Our study provides pre-clinical evidence to support the feasibility of treating MS by transplantation of iPSC-derived NSCs.展开更多
Graves' disease,the production of thyroid-stimulating hormone receptor-stimulating antibodies leading to hyperthyroidism,is one of the most common forms of human autoimmune disease.It is widely agreed that complex...Graves' disease,the production of thyroid-stimulating hormone receptor-stimulating antibodies leading to hyperthyroidism,is one of the most common forms of human autoimmune disease.It is widely agreed that complex diseases are not controlled simply by an individual gene or DNA variation but by their combination.Single nucleotide polymorphisms(SNPs),which are the most common form of DNA variation,have great potential as a medical diagnostic tool.In this paper,the P-value is used as a SNP pre-selection criterion,and a wrapper algorithm with binary particle swarm optimization is used to find the rule for discriminating between affected and control subjects.We analyzed the association between combinations of SNPs and Graves' disease by investigating 108 SNPs in 384 cases and 652 controls.We evaluated our method by differentiating between cases and controls in a five-fold cross validation test,and it achieved a 72.9% prediction accuracy with a combination of 17 SNPs.The experimental results showed that SNPs,even those with a high P-value,have a greater effect on Graves' disease when acting in a combination.展开更多
文摘AIM: To characterize gene polymorphism of several cytokine gene in-patients with AIH and PBC and to analyze the difference of the polymorphism distribution between Chinese patients and healthy controls.METHODS: The study population consisted of 62 patients with AIH, and 77 patients with PBC. The genetic profile of four cytokines was analyzed by restriction fragmentlength polymorphism after specific PCR amplification (PCR-RFLP) or sequence-specific primers PCR (SSP-PCR). The analyzed gene polymorphism included interleukin-1 (IL-1) (at position +3 953 and IL-1RN intron 2), IL-6 (atposition -174), IL-10 promoter (at position -1 082, -819, and -592). The control group consisted of 160 healthyblood donors.RESULTS: The majority of Chinese people including patients and healthy controls exhibited IL-1B 1,1genotype, and there was no significant difference in AIH, PBC patients and controls. There were highly statistically significant differences in the distribution of the IL-1RN gene polymorphism between the patients with PBCcompared with controls. The frequency of IL-1RN 1,1was significantly higher (90.9% vs 79.4%, P = 0.03)and the frequency of IL-1RN 1,2 was significantly lower in PBC patients (6.5% vs 17.5%, P = 0.01). No statistical difference was observed between AIH patients and controls. All of the 160 healthy controls and 62 cases of AIH patients exhibited IL-6-174GG genotype, and there were four cases, which expressed IL-6-174GC genotype in 77 cases of PBC patients. The frequency of IL-6-174GC was markedly significantly higher in PBC patients compared with controls (5.2% vs 0%, P = 0.004). No statistically significant difference was found in the distribution of IL-10 promoter genotype in AIH and PBC patients compared with controls. CONCLUSION: The polymorphisms of IL-1RN and IL-6 -174G/C appear to be associated with PBC in Chinese patients.
基金supported by thegrant from China Scholarship Council(Grant No.[2008]3019)
文摘Vitamin D is a seco-steroid involved in calcium and phosphorus metabolism,and bone formation and mineralization, through binding to a specific nuclear receptor,vitamin D receptor（VDR）.Besides its well-established functions on bone health,multiple lines of evidence have indicated the immunomodulatory roles of vitamin D.Vitamin D can affect both innate and adaptive immunity,and prevent autoimmune responses efficiently.Vitamin D regulates the immune responses by suppressing T cell proliferation and modulating macrophage functions.Epidemiological studies have shown that vitamin D deficiency is associated with multiple diseases such as rickets and cancer.Moreover,associations between vitamin D and autoimmune diseases have been confirmed in multiple sclerosis（MS）,rheumatoid arthritis（RA）,etc.The present review mainly summarized the recent findings on the immunomodulatory role of vitamin D in various disorders,with special focus on its role in MS,an autoimmune disease of the nervous system.
基金supported by the China National Basic Research Program(2013CB966901,2012CBA01303)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA01040108)+1 种基金National Thousand Young Talents Program to Tongbiao Zhaothe National Natural Science Foundation of China Program((31271592,31570995)to Tongbiao Zhao,(31400831)to Jiani Cao)
文摘Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and there are currently no effective treatments. The development of neural stem cell(NSC) transplantation provides a promising strategy to treat neurodegenerative disease. However, the limited availability of NSCs prevents their application in neural disease therapy. In this study, we generated NSCs from induced pluripotent stem cells(iPSCs) and transplanted these cells into mice with experimental autoimmune encephalomyelitis(EAE), a model of MS. The results showed that transplantation of iPSC-derived NSCs dramatically reduced T cell infiltration and ameliorated white matter damage in the treated EAE mice. Correspondingly, the disease symptom score was greatly decreased, and motor ability was dramatically rescued in the iPSC-NSC-treated EAE mice, indicating the effectiveness of using iPSC-NSCs to treat MS. Our study provides pre-clinical evidence to support the feasibility of treating MS by transplantation of iPSC-derived NSCs.
基金supported by the National Natural Science Foundation of China (Grant No. 60774086)the Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20090201110027)
文摘Graves' disease,the production of thyroid-stimulating hormone receptor-stimulating antibodies leading to hyperthyroidism,is one of the most common forms of human autoimmune disease.It is widely agreed that complex diseases are not controlled simply by an individual gene or DNA variation but by their combination.Single nucleotide polymorphisms(SNPs),which are the most common form of DNA variation,have great potential as a medical diagnostic tool.In this paper,the P-value is used as a SNP pre-selection criterion,and a wrapper algorithm with binary particle swarm optimization is used to find the rule for discriminating between affected and control subjects.We analyzed the association between combinations of SNPs and Graves' disease by investigating 108 SNPs in 384 cases and 652 controls.We evaluated our method by differentiating between cases and controls in a five-fold cross validation test,and it achieved a 72.9% prediction accuracy with a combination of 17 SNPs.The experimental results showed that SNPs,even those with a high P-value,have a greater effect on Graves' disease when acting in a combination.
