目的探讨Rab40家族在肝癌中的表达及临床意义。方法收集TIMER2.0数据库和The Human Protein Atlas数据库中肝癌数据集,分析Rab40家族在肝癌患者中的表达水平,并分析其表达与患者临床病理资料、肿瘤微环境免疫细胞浸润的关系;收集Kaplan-...目的探讨Rab40家族在肝癌中的表达及临床意义。方法收集TIMER2.0数据库和The Human Protein Atlas数据库中肝癌数据集,分析Rab40家族在肝癌患者中的表达水平,并分析其表达与患者临床病理资料、肿瘤微环境免疫细胞浸润的关系;收集Kaplan-Meier Plotter数据库中肝癌数据集,分析Rab40b和Rab40c的表达水平与肝癌患者预后的关系。结果肝癌组织中的Rab40a、Rab40al、Rab40b和Rab40c表达水平显著高于癌旁组织,差异具有统计学意义(P<0.05)。Rab40c高表达与肝癌患者TNM分期可能存在相关性(P=0.064)。Rab40b、Rab40c高表达肝癌患者的总生存期(OS)、无复发生存期(RFS)短于Rab40b、Rab40c低表达肝癌患者,差异具有统计学意义(P<0.05)。肝癌组织中Rab40b的表达水平与肿瘤微环境的B细胞和CD8^(+)T细胞无关(P>0.05),而与CD4^(+)T细胞、巨噬细胞、中性粒细胞和树突状细胞密切相关,差异具有统计学意义(P<0.05)。肝癌组织中Rab40c的表达水平与肿瘤微环境的B细胞、CD8^(+)T细胞、CD4^(+)T细胞、巨噬细胞、中性粒细胞和树突状细胞密切相关,差异具有统计学意义(P<0.05)。结论Rab40家族在肝癌中高表达,尤其是Rab40b和Rab40c,通过影响肿瘤微环境中的免疫细胞促进肝癌的发生、发展,可作为肝癌治疗和预后的潜在生物标志物。展开更多
Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T...Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.展开更多
Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotro...Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotrophic factor(BDNF)are believed to be associated with the neurotoxic effects of Aβpeptide.To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ_(1-40)-induced retinal injury in Sprague-Dawley rats,we treated rats by intravitreal administration of phosphate-buffered saline(control),Aβ_(1-40)(5 nM),or Aβ_(1-40)(5 nM)combined with BDNF(1μg/mL).We found that intravitreal administration of Aβ_(1-40)induced retinal ganglion cell apoptosis.Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ_(1-40)group than in the control and BDNF groups.In the Aβ_(1-40)group,low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression.BDNF abolished Aβ_(1-40)-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression.These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ_(1-40)by activating the BDNF-TrkB signaling pathway in rats.展开更多
Soybean(Glycine max)is a major oil and feed crop worldwide.Soybean mosaic virus(SMV)is a globally occurring disease that severely reduces the yield and quality of soybean.Here,we characterized the role of the clock ge...Soybean(Glycine max)is a major oil and feed crop worldwide.Soybean mosaic virus(SMV)is a globally occurring disease that severely reduces the yield and quality of soybean.Here,we characterized the role of the clock gene TIMING OF CAB EXPRESSION 1b(GmTOC1b)in the resistance of soybean to SMV.Homozygous Gmtoc1b mutants exhibited increased tolerance to SMV strain SC3 due to the activation of programmed cell death triggered by a hypersensitive response.Transcriptome deep sequencing and RT-qPCR analysis suggested that GmTOC1b likely regulates the expression of target genes involved in the salicylic acid(SA)signaling pathway.GmTOC1b binds to the promoter of GmWRKY40,which encodes a protein that activates the expression of SA-mediated defense-related genes.Moreover,we revealed that the GmTOC1bH1 haplotype,which confers increased tolerance to SMV,was artificially selected in improved cultivars from the Northern and Huang-Huai regions of China.Our results therefore identify a previously unknown SMV resistance component that could be deployed in the molecular breeding of soybean to enhance SMV resistance.展开更多
文摘目的探讨Rab40家族在肝癌中的表达及临床意义。方法收集TIMER2.0数据库和The Human Protein Atlas数据库中肝癌数据集,分析Rab40家族在肝癌患者中的表达水平,并分析其表达与患者临床病理资料、肿瘤微环境免疫细胞浸润的关系;收集Kaplan-Meier Plotter数据库中肝癌数据集,分析Rab40b和Rab40c的表达水平与肝癌患者预后的关系。结果肝癌组织中的Rab40a、Rab40al、Rab40b和Rab40c表达水平显著高于癌旁组织,差异具有统计学意义(P<0.05)。Rab40c高表达与肝癌患者TNM分期可能存在相关性(P=0.064)。Rab40b、Rab40c高表达肝癌患者的总生存期(OS)、无复发生存期(RFS)短于Rab40b、Rab40c低表达肝癌患者,差异具有统计学意义(P<0.05)。肝癌组织中Rab40b的表达水平与肿瘤微环境的B细胞和CD8^(+)T细胞无关(P>0.05),而与CD4^(+)T细胞、巨噬细胞、中性粒细胞和树突状细胞密切相关,差异具有统计学意义(P<0.05)。肝癌组织中Rab40c的表达水平与肿瘤微环境的B细胞、CD8^(+)T细胞、CD4^(+)T细胞、巨噬细胞、中性粒细胞和树突状细胞密切相关,差异具有统计学意义(P<0.05)。结论Rab40家族在肝癌中高表达,尤其是Rab40b和Rab40c,通过影响肿瘤微环境中的免疫细胞促进肝癌的发生、发展,可作为肝癌治疗和预后的潜在生物标志物。
基金supported by National Major Science and Technology Projects of China 2017ZX10105015-001-002。
文摘Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.
基金supported by the Ministry of Higher Education,Government of Malaysia,No.FRGS/2/2014/SG03/UITM/02/2 UiTM IRMI file No.600-RMI/FRGS 5/3(111/2014),toⅡYayasan Penyelidikan Otak,Minda dan Neurosains Malaysia(YPOMNM),No.YPOMNM/2019-04(2)UiTM IRMI No.100-IRMI/PRI 16/6/2(010/2019),to MAML。
文摘Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotrophic factor(BDNF)are believed to be associated with the neurotoxic effects of Aβpeptide.To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ_(1-40)-induced retinal injury in Sprague-Dawley rats,we treated rats by intravitreal administration of phosphate-buffered saline(control),Aβ_(1-40)(5 nM),or Aβ_(1-40)(5 nM)combined with BDNF(1μg/mL).We found that intravitreal administration of Aβ_(1-40)induced retinal ganglion cell apoptosis.Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ_(1-40)group than in the control and BDNF groups.In the Aβ_(1-40)group,low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression.BDNF abolished Aβ_(1-40)-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression.These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ_(1-40)by activating the BDNF-TrkB signaling pathway in rats.
基金the National Natural Science Foundation of China(32001502,32001507)the China Postdoctoral Science Foundation(2020M682655)+3 种基金the top ten critical priorities of Agricultural Science and Technology Innovations for the 14th Five-Year Plan of Guangdong Province(2022SDZG05)Science and Technology Innovation Team of Soybean Modern Seed Industry In Hebei Province(21326313D-4)Innovation Research Project of Coarse Cereals Specialty in Guizhou Province[2019[4012]]the Regional First-class Discipline of Ecology in Guizhou Province(XKTJ[2020]22).
文摘Soybean(Glycine max)is a major oil and feed crop worldwide.Soybean mosaic virus(SMV)is a globally occurring disease that severely reduces the yield and quality of soybean.Here,we characterized the role of the clock gene TIMING OF CAB EXPRESSION 1b(GmTOC1b)in the resistance of soybean to SMV.Homozygous Gmtoc1b mutants exhibited increased tolerance to SMV strain SC3 due to the activation of programmed cell death triggered by a hypersensitive response.Transcriptome deep sequencing and RT-qPCR analysis suggested that GmTOC1b likely regulates the expression of target genes involved in the salicylic acid(SA)signaling pathway.GmTOC1b binds to the promoter of GmWRKY40,which encodes a protein that activates the expression of SA-mediated defense-related genes.Moreover,we revealed that the GmTOC1bH1 haplotype,which confers increased tolerance to SMV,was artificially selected in improved cultivars from the Northern and Huang-Huai regions of China.Our results therefore identify a previously unknown SMV resistance component that could be deployed in the molecular breeding of soybean to enhance SMV resistance.
