Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Ac...Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Academy of Medical Sciences Initiative for Innovative Medicine on Tumor Immunology held in Beijing, China, on May 12, 2017, a number of speakers reported new findings and ongoing studies on immune-related diseases such as cancer, fibrotic disease, diabetes, and others. A considerably insightful overview was provided on cancer immunity, tumor microenvironments,and new immunotherapy for cancer. In addition, chronic inflammatory diseases were discussed. These findings may offer new insights into targeted immunotherapy.展开更多
Background: Recent studies have indicated that an imbalance of gut microbiota is associated with the development of type 1 diabetes mellitus (TI DM) and there is no literature regarding it in Chinese children yet. ...Background: Recent studies have indicated that an imbalance of gut microbiota is associated with the development of type 1 diabetes mellitus (TI DM) and there is no literature regarding it in Chinese children yet. The aim of this study was to evaluate the alteration of gut microbiota between children with newly diagnosed T 1DM and healthy controls and to determine if gut microbiota could partly explain the etiology of this disease. Methods: A case-control study was carried out with 15 children with T 1 DM and 15 healthy children. The fecal bacteria composition was investigated by high-throughput sequencing of the V3-V4 region of the 16S rDNA gene and analyzed by the estimators of community richness (Chao) indexes. Results: There was a notable lower richness of fecal bacteria in T1DM group than controls (156.53 ± 36.96 vs. 130.0 ± 32.85, P - 0.047). At the genus level, the composition of Blautia was increased in T 1 DM group than control group whereas the composition of Haemophilus, Lachnospira, Dialister, and Acidaminococcus was decreased. In addition, we found that the percentage of Blautia was correlated positively with HbA 1 c (p = 0.40, P - 0.031), the numbers of T1DM autoantibodies (p = 0.42, P = 0.023), and the titers of tyrosine phosphatase autoantibodies (IA-2) (p= 0.82, P = 0.000) in the study. Conclusions: This study showed that gut microbiota was associated with the development of T 1DM by affecting the autoimmunity, and the results suggested a potential therapy for T1DM via modulating the gut microbiota.展开更多
Background: Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variant...Background: Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKALI, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population.Methods: Twelve single nucleotide polymorphisms (rs7756992/rs10946398 in CDKAL1, rsl 111875 in HHEA; rs391300 in SRR, rs17584499 in PTPRD. rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5) were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed.Results: Birthweight was inversely associated with CDKAL 1-rs 10946398 (β = -41 g [95% confidence interval [CI]: -80, 3], P= 0.034), common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight (β = 36 g [95% CI: -72, -0.2], P = 0.048). The risk allele in SRR showed a trend toward a reduction ofbirthweight (P =0.085). Conclusions: This study identified the association between type 2 diabetes risk variants in CDKAL 1 and birthweight in Chinese Hart individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.展开更多
Methods of performing insulin clamps vary between laboratories.Here we present a protocol of insulin clamping in conscious mice,with the significant advantage of avoiding multiple surgical catheterizations and non-phy...Methods of performing insulin clamps vary between laboratories.Here we present a protocol of insulin clamping in conscious mice,with the significant advantage of avoiding multiple surgical catheterizations and non-physiologic metabolism during the induction of anesthesia.Using this technique we also established a new method for measuring hepa tic glucose production(HGP)using a fuorescent D-glucose analog,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglu-cose(2-NBDG).To prove the reliability and feasibility of this method,whole-body insulin sensitivity was compared between conscious normal ICR mice and diabetic KK^(Ay) mice using the insulin clamp.Basal and clamp HGP was compared between normal C57 mice and diabetic db/db mice by using the modified clamp with 2-NBDG as a tracer.The glucose infusion rate(GIR),an index of insulin sensitivity,was significantly lower in KKAy mice than normal ICR mice.(6.2±1.3 mg/kg/min vs.31.3±2.9 mg/kg/min,P<0.001).The db/db mice also showed higher basal hepatic glucose production(25.8±2.2 mg/kg/min vs.16.7±2.5 mg/kg/min,P<0.05),higher clamp HGP after insulin suppression(7.3±1.0 mg/kg/min vs.0 mg/kg/min,P<0.001),and lower GIR(71.6±2.8 mg/kg/min vs.15.2±1.6 mg/kg/min,P<0.001)than that obtained with normal C57 mice.In conclusion,this is the first report of the application of 2-NBDG,rather than isotopic tracers,for the determination of HGP in vivo.展开更多
The study illustrate the inner correlation between global DNA methylation variation and different birth weights. Infant birth weight was used to identify cases and controls. Cord blood and placentas were collected. We...The study illustrate the inner correlation between global DNA methylation variation and different birth weights. Infant birth weight was used to identify cases and controls. Cord blood and placentas were collected. We performed DNA methylation profiling of bisulphite‐converted DNA. We have identified many differentially methylated Cp G sites in experimental groups; these sites involved in hundreds of signalings. Among these, more than ten pathways were referred to the glucose and lipid metabolism. Methylation changes in the insulin‐signaling pathway(ISP), adipocytokine signaling pathway(ASP) and MAPK signaling pathway are involved in the fetal programming of diabetes.展开更多
基金supported by grants of 81530093 from the National Natural Science Foundation of China81661128007, 81472653 and 81530080 from National Natural Science Foundation of China+26 种基金supported by grants of 31390431 from the National Natural Science Foundation of Chinasupported by grants of Natural Sciences Foundation of China(31301007 and 81272525)supported by grants of 81622010 from the National Natural Science Foundation of Chinasupported by grants of 81472717 and 81673474 from the National Natural Science Foundation of China81661128007, 81472653 and 81530080 from National Natural Science Foundation of Chinasupported by grants of 81400286 and 81530093 from the National Natural Science Foundation of Chinasupported by grants of 81400140 from the National Natural Science Foundation of Chinasupported by grants of 81503128 from the National Natural Science Foundation of China2016I2M-1-008 from Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciencessupported by grants of 2014CB542103 from National Basic Research Program of China81502473 from National Natural Science Fund for Young Scholars of Chinasupported by US National Institutes of Health grants (CA217510, CA123088, CA099985, CA193136 and CA152470)supported by grants from the Canadian Institutes of Health Research(FRN 123516 and 152954)the Ontario Institute for Cancer Research(ORBiT)supported by NIH grant GM072744Ministry of Science and Technology of China grant 2016YFA0101100the Fundamental Research Fund for the Central University(No. 2017KFQWJX002) from Huazhong University of Science and TechnologyCore fund (Wang2016) for Development of Cell and Gene Therapy Centre of Academy of Medical Sciences,Zhengzhou UniversityThe MRC (MR/M015696/1)2017YFA0205400 from Ministry of Science and Technology of China2016ZX310190 and 2016ZX320014 from Central Public-interest Scientific Institution Basal Research Fund7162133 from Beijing Natural Science Foundation2016-I2M-4-001 from CAMS Innovation Fund for Medical Sciences2016-I2M-1-007 from the CAMS Innovation Fund for Medical Sciences2016-I2M-1010 from the CAMS Innovation Fund for Medical Sciences2016-I2M-1011 from the CAMS Innovation Fund for Medical Sciences2016-I2M-1008 from CAMS Innovation Fund for Medical Sciences
文摘Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Academy of Medical Sciences Initiative for Innovative Medicine on Tumor Immunology held in Beijing, China, on May 12, 2017, a number of speakers reported new findings and ongoing studies on immune-related diseases such as cancer, fibrotic disease, diabetes, and others. A considerably insightful overview was provided on cancer immunity, tumor microenvironments,and new immunotherapy for cancer. In addition, chronic inflammatory diseases were discussed. These findings may offer new insights into targeted immunotherapy.
文摘Background: Recent studies have indicated that an imbalance of gut microbiota is associated with the development of type 1 diabetes mellitus (TI DM) and there is no literature regarding it in Chinese children yet. The aim of this study was to evaluate the alteration of gut microbiota between children with newly diagnosed T 1DM and healthy controls and to determine if gut microbiota could partly explain the etiology of this disease. Methods: A case-control study was carried out with 15 children with T 1 DM and 15 healthy children. The fecal bacteria composition was investigated by high-throughput sequencing of the V3-V4 region of the 16S rDNA gene and analyzed by the estimators of community richness (Chao) indexes. Results: There was a notable lower richness of fecal bacteria in T1DM group than controls (156.53 ± 36.96 vs. 130.0 ± 32.85, P - 0.047). At the genus level, the composition of Blautia was increased in T 1 DM group than control group whereas the composition of Haemophilus, Lachnospira, Dialister, and Acidaminococcus was decreased. In addition, we found that the percentage of Blautia was correlated positively with HbA 1 c (p = 0.40, P - 0.031), the numbers of T1DM autoantibodies (p = 0.42, P = 0.023), and the titers of tyrosine phosphatase autoantibodies (IA-2) (p= 0.82, P = 0.000) in the study. Conclusions: This study showed that gut microbiota was associated with the development of T 1DM by affecting the autoimmunity, and the results suggested a potential therapy for T1DM via modulating the gut microbiota.
基金Source of Support: This study was supported by grants from the Natural Sciences Foundation of Beijing (No. 5072042), National Natural Science Foundation of China (No. 81170736), National Key Program of Clinical Science. Conflict of Interest: None declared.
文摘Background: Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKALI, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population.Methods: Twelve single nucleotide polymorphisms (rs7756992/rs10946398 in CDKAL1, rsl 111875 in HHEA; rs391300 in SRR, rs17584499 in PTPRD. rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5) were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed.Results: Birthweight was inversely associated with CDKAL 1-rs 10946398 (β = -41 g [95% confidence interval [CI]: -80, 3], P= 0.034), common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight (β = 36 g [95% CI: -72, -0.2], P = 0.048). The risk allele in SRR showed a trend toward a reduction ofbirthweight (P =0.085). Conclusions: This study identified the association between type 2 diabetes risk variants in CDKAL 1 and birthweight in Chinese Hart individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.
基金This work was supported by the grants from the Key Project of the National Twelfth-Five Year Research Program of China and National S&T Major Special Project on Major New Drug Innovation(No.2012ZX09301002-004).
文摘Methods of performing insulin clamps vary between laboratories.Here we present a protocol of insulin clamping in conscious mice,with the significant advantage of avoiding multiple surgical catheterizations and non-physiologic metabolism during the induction of anesthesia.Using this technique we also established a new method for measuring hepa tic glucose production(HGP)using a fuorescent D-glucose analog,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglu-cose(2-NBDG).To prove the reliability and feasibility of this method,whole-body insulin sensitivity was compared between conscious normal ICR mice and diabetic KK^(Ay) mice using the insulin clamp.Basal and clamp HGP was compared between normal C57 mice and diabetic db/db mice by using the modified clamp with 2-NBDG as a tracer.The glucose infusion rate(GIR),an index of insulin sensitivity,was significantly lower in KKAy mice than normal ICR mice.(6.2±1.3 mg/kg/min vs.31.3±2.9 mg/kg/min,P<0.001).The db/db mice also showed higher basal hepatic glucose production(25.8±2.2 mg/kg/min vs.16.7±2.5 mg/kg/min,P<0.05),higher clamp HGP after insulin suppression(7.3±1.0 mg/kg/min vs.0 mg/kg/min,P<0.001),and lower GIR(71.6±2.8 mg/kg/min vs.15.2±1.6 mg/kg/min,P<0.001)than that obtained with normal C57 mice.In conclusion,this is the first report of the application of 2-NBDG,rather than isotopic tracers,for the determination of HGP in vivo.
基金supported by the National Natural Science Foundation of China(NSFC),project number is 81170736 and 81570715
文摘The study illustrate the inner correlation between global DNA methylation variation and different birth weights. Infant birth weight was used to identify cases and controls. Cord blood and placentas were collected. We performed DNA methylation profiling of bisulphite‐converted DNA. We have identified many differentially methylated Cp G sites in experimental groups; these sites involved in hundreds of signalings. Among these, more than ten pathways were referred to the glucose and lipid metabolism. Methylation changes in the insulin‐signaling pathway(ISP), adipocytokine signaling pathway(ASP) and MAPK signaling pathway are involved in the fetal programming of diabetes.