目的 探讨抗生素(antibiotic,ATB)联合抗程序性细胞死亡蛋白1 (programmed cell death protein 1,PD1)抗体免疫治疗对小鼠肝癌疗效的影响。方法 建立雄性BALB/cH_(22)荷瘤小鼠模型,于建模后腹腔注射抗PD1抗体(250μg/只)免疫治疗,同时...目的 探讨抗生素(antibiotic,ATB)联合抗程序性细胞死亡蛋白1 (programmed cell death protein 1,PD1)抗体免疫治疗对小鼠肝癌疗效的影响。方法 建立雄性BALB/cH_(22)荷瘤小鼠模型,于建模后腹腔注射抗PD1抗体(250μg/只)免疫治疗,同时给予小鼠灌胃头孢曲松钠(100 mg/kg)+盐酸林可霉素(200 mg/kg),设灌胃生理盐水的正常对照组(0.2 mL/只),每组8只。通过小鼠肿瘤体积、肿瘤组织的苏木素-伊红(HE)染色和脾指数评估ATB与抗PD1抗体联合治疗的抗肿瘤效果;ELISA法检测小鼠血清中IL-2、IL-10、IFNγ细胞因子分泌水平;流式细胞术分析小鼠淋巴细胞中CD3^(+)和CD8^(+)T细胞比例;免疫组化(immunohistochemistry,IHC)法检测小鼠肿瘤组织中CD3和CD8表达水平。结果 ATB与抗PD1抗体联合治疗对肿瘤生长有显著抑制作用,上调了T淋巴细胞中CD3^(+)和CD8^(+)T细胞比例及IL-2、IL-10、IFNγ细胞因子分泌水平;通过上调肿瘤组织中CD3和CD8表达水平来调节T细胞免疫功能,以持续激活免疫系统,抑制肿瘤。结论 窄谱ATB可能通过改善免疫功能以促进抗体免疫治疗对肿瘤的抑制效果。展开更多
Type 1 diabetes(T1D)is an autoimmune disease that resulted from the severe destruction of the insulin-producingβcells in the pancreases of individuals with a genetic predisposition.Genome-wide studies have identified...Type 1 diabetes(T1D)is an autoimmune disease that resulted from the severe destruction of the insulin-producingβcells in the pancreases of individuals with a genetic predisposition.Genome-wide studies have identified HLA and other risk genes associated with T1D susceptibility in humans.However,evidence obtained from the incomplete concordance of diabetes incidence among monozygotic twins suggests that environmental factors also play critical roles in T1D pathogenesis.Epigenetics is a rapidly growing field that serves as a bridge to link T1D risk genes and environmental exposures,thereby modulating the expression of critical genes relevant to T1D development beyond the changes of DNA sequences.Indeed,there is compelling evidence that epigenetic changes induced by environmental insults are implicated in T1D pathogenesis.Herein,we sought to summarize the recent progress in terms of epigenetic mechanisms in T1D initiation and progression,and discuss their potential as biomarkers and therapeutic targets in the T1D setting.展开更多
Long non-coding RNAs(lncRNAs)exhibit a length more than 200 nucleotides and they are characterized by non-coding RNAs(ncRNA)not encoded into proteins.Over the past few years,the role and development of lncRNAs have ar...Long non-coding RNAs(lncRNAs)exhibit a length more than 200 nucleotides and they are characterized by non-coding RNAs(ncRNA)not encoded into proteins.Over the past few years,the role and development of lncRNAs have aroused the rising attention of researchers.To be specific,KCNQ1OT1,the KCNQ1 opposite strand/antisense transcript 1,is clearly classified as a regulatory ncRNA.KCNQ1OT1 is capable of interacting with miRNAs,RNAs and proteins,thereby affecting gene expression and various cell functions(e.g.,cell proliferation,migration,epithelialemesenchymal transition(EMT),apoptosis,viability,autophagy and inflammation).KCNQ1OT1 is dysregulated in a wide range of human diseases(e.g.,cardiovascular disease,cancer,diabetes,osteoarthritis,osteoporosis and cataract),and it is speculated to act as a therapeutic target for treating various human diseases.On the whole,this review aims to explore the biological functions,underlying mechanisms and pathogenic roles of KCNQ1OT1 in human diseases.展开更多
Let μ be a Radon measure on Rd which may be non-doubling. The only condition that μ must satisfy is μ（B（x,r）） ≤ Urn for all x∈Rd, r 〉 0 and for some fixed 0 〈 n 〈 d. In this paper, under this assumption, w...Let μ be a Radon measure on Rd which may be non-doubling. The only condition that μ must satisfy is μ（B（x,r）） ≤ Urn for all x∈Rd, r 〉 0 and for some fixed 0 〈 n 〈 d. In this paper, under this assumption, we prove that 0-type Calder6n-Zygmund operator which is bounded on L2 （μ） is also bounded from L^∞（μ） into RBMO （μ） and from Hb （μ） into L1（μ）. According to the interpolation theorem introduced by Tolsa, the LP（μ）-boundedness （1 〈 p 〈 ∞） is established for θ-type Calder6n-Zygmund operators. Via a sharp maximal operator, it is shown that commutators and multilinear commutators of θ-type CMderθn-Zygmundoperator with RBMO （μ） function are bounded on LP（μ） （1 〈 p 〈 ∞）.展开更多
In recent years, large numbers of non-coding RNAs （ncR- NAs） have been identified in C. elegans but their functions are still not well studied. In C. elegans, CEP-1 is the sole homolog of the p53 family of genes. In...In recent years, large numbers of non-coding RNAs （ncR- NAs） have been identified in C. elegans but their functions are still not well studied. In C. elegans, CEP-1 is the sole homolog of the p53 family of genes. In order to obtain transcription profiles of ncRNAs regulated by CEP-1 under normal and UV stressed conditions, we applied the ＇not-so- random＇ hexamers priming strategy to RNA sequencing in C. elegans, This NSR-seq strategy efficiently depleted rRNA transcripts from the samples and showed high technical replicability. We identified more than 1,000 ncR- NAs whose apparent expression was repressed by CEP-1, while around 200 were activated. Around 40% of the CEP-1 activated ncRNAs promoters contain a putative CEP-1- binding site. CEP-1 regulated ncRNAs were frequently clustered and concentrated on the X chromosome. These results indicate that numerous ncRNAs are involved in CEP-1 transcriptional network and that these are espe- cially enriched on the X chromosome in C. elegans.展开更多
基金supported by grants from the Ministry of Science and Technology(Nos.2016YFC1305002 and 2017YFC1309603)the National Natural Science Foundation of China(Nos.81530024,91749207,81920108009,81770823,and 81670729)+3 种基金the NHC Drug Discovery Program(No.2017ZX09304022-07)the Department of Science and Technology of Hubei State(No.2017ACA096)the Integrated Innovative Team for Major Human Disease Programs of Tongji Medical College,Huazhong University of Science and Technologythe Innovative Funding for Translational Research from Tongji Hospital.
文摘Type 1 diabetes(T1D)is an autoimmune disease that resulted from the severe destruction of the insulin-producingβcells in the pancreases of individuals with a genetic predisposition.Genome-wide studies have identified HLA and other risk genes associated with T1D susceptibility in humans.However,evidence obtained from the incomplete concordance of diabetes incidence among monozygotic twins suggests that environmental factors also play critical roles in T1D pathogenesis.Epigenetics is a rapidly growing field that serves as a bridge to link T1D risk genes and environmental exposures,thereby modulating the expression of critical genes relevant to T1D development beyond the changes of DNA sequences.Indeed,there is compelling evidence that epigenetic changes induced by environmental insults are implicated in T1D pathogenesis.Herein,we sought to summarize the recent progress in terms of epigenetic mechanisms in T1D initiation and progression,and discuss their potential as biomarkers and therapeutic targets in the T1D setting.
基金The work was supported by the grants from National Natural Science Foundation of China(No.81773959 to C.F.Yuan and 81974528 to C.F.Yuan)the central government guides the special funds for the development of local science and technology(No.2020ZYYD016 to C.F.Yuan)Health commission of Hubei Province scientific research project in PR China(No.WJ2019H527 to C.F.Yuan).
文摘Long non-coding RNAs(lncRNAs)exhibit a length more than 200 nucleotides and they are characterized by non-coding RNAs(ncRNA)not encoded into proteins.Over the past few years,the role and development of lncRNAs have aroused the rising attention of researchers.To be specific,KCNQ1OT1,the KCNQ1 opposite strand/antisense transcript 1,is clearly classified as a regulatory ncRNA.KCNQ1OT1 is capable of interacting with miRNAs,RNAs and proteins,thereby affecting gene expression and various cell functions(e.g.,cell proliferation,migration,epithelialemesenchymal transition(EMT),apoptosis,viability,autophagy and inflammation).KCNQ1OT1 is dysregulated in a wide range of human diseases(e.g.,cardiovascular disease,cancer,diabetes,osteoarthritis,osteoporosis and cataract),and it is speculated to act as a therapeutic target for treating various human diseases.On the whole,this review aims to explore the biological functions,underlying mechanisms and pathogenic roles of KCNQ1OT1 in human diseases.
基金Supported by National Natural Science Foundation of China (No.10371087)Natural Science Foundation of Education Committee of Anhui Province (No.KJ2011A138, No.KJ2012B116)
文摘Let μ be a Radon measure on Rd which may be non-doubling. The only condition that μ must satisfy is μ（B（x,r）） ≤ Urn for all x∈Rd, r 〉 0 and for some fixed 0 〈 n 〈 d. In this paper, under this assumption, we prove that 0-type Calder6n-Zygmund operator which is bounded on L2 （μ） is also bounded from L^∞（μ） into RBMO （μ） and from Hb （μ） into L1（μ）. According to the interpolation theorem introduced by Tolsa, the LP（μ）-boundedness （1 〈 p 〈 ∞） is established for θ-type Calder6n-Zygmund operators. Via a sharp maximal operator, it is shown that commutators and multilinear commutators of θ-type CMderθn-Zygmundoperator with RBMO （μ） function are bounded on LP（μ） （1 〈 p 〈 ∞）.
文摘In recent years, large numbers of non-coding RNAs （ncR- NAs） have been identified in C. elegans but their functions are still not well studied. In C. elegans, CEP-1 is the sole homolog of the p53 family of genes. In order to obtain transcription profiles of ncRNAs regulated by CEP-1 under normal and UV stressed conditions, we applied the ＇not-so- random＇ hexamers priming strategy to RNA sequencing in C. elegans, This NSR-seq strategy efficiently depleted rRNA transcripts from the samples and showed high technical replicability. We identified more than 1,000 ncR- NAs whose apparent expression was repressed by CEP-1, while around 200 were activated. Around 40% of the CEP-1 activated ncRNAs promoters contain a putative CEP-1- binding site. CEP-1 regulated ncRNAs were frequently clustered and concentrated on the X chromosome. These results indicate that numerous ncRNAs are involved in CEP-1 transcriptional network and that these are espe- cially enriched on the X chromosome in C. elegans.
