The effects of dietary zinc on the immune organs and cellular immunity were investigated in the rats of zinc-deficient(ZD), zinc-excessive(ZE), paired feeding(PF) and ad libitus(AL) groups. The findings were as follow...The effects of dietary zinc on the immune organs and cellular immunity were investigated in the rats of zinc-deficient(ZD), zinc-excessive(ZE), paired feeding(PF) and ad libitus(AL) groups. The findings were as follows: (1) The weight of the thymus and spleen and the ratio with the body weight, the size of the cells,the production of thymic peptides and thymin activity were significantly lower in ZD and ZE groups than in PF and AL groups. (2) The total number of the cells in G_0/G_1 phase of T-and B-cells and bone marrow cells were significantly higher in ZD and ZF groups than in PF and AL groups while that of the cells in S and G_2/M phases were significantly lower in ZD and ZE groups than in PF and AL groups. (3) The cellular DNA, RNA and protein content in the thymus, spleen and bone marrow were significantly lower in ZD and ZE groups than in PF and AL groups.(4) The ￣3H-TdR incorporation rate of splenic T-and B-cells , IL-2 activity, plasma level of TNF and nitrogen oxide(NO) were significantly lower in ZD group than in PF group. (5) The leucocyte count of the perpheral blood,the percentage of lymphocytes, the bacteriocidal activity of phagocytes, and the phagocytic rate and index of abdominal phagocytes were significantly lower in ZD and ZE groups than in PF and AL groups. These findings indicate that an adequate amount of dietary zinc is essential for the development of immune organs and the promotion of cellular immunity while deficiency or excess of zinc is able to damage the immune function.展开更多
Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)re...Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.展开更多
Studied features of cellular and humoral factors of immune system and activation markers of lymphocytes at breast cancer patients.Analyzed biophysical parameters of lymphocyte superficial membranes of periphery blood ...Studied features of cellular and humoral factors of immune system and activation markers of lymphocytes at breast cancer patients.Analyzed biophysical parameters of lymphocyte superficial membranes of periphery blood of breast cancer patients.Features of immune system reaction were:expressed Т - cellular immunodeficiency,deficiency of CD4+Т-helpers/inducers against raised expression of СD8+Т-lymphocyte,suppression of immunoregulatory index,imbalance of immunity humoral link,activity of expression CD16 + and CD56 + on natural killers and rising of expression CD38 + and CD95 + on lymphocytes.Studying of biophysical parameters of lymphocytes superficial membranes has allowed to reveal statistically significant changes characterized by intensifying of electric field and rising ofmicroviscosity,obviously leading to disappearance or weakening of intercellular interactions.展开更多
Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one ...Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.展开更多
Cancer immunotherapy using immune-checkpoint inhibitors(ICIs)has revolutionized the field of cancer treatment;however,ICI efficacy is constrained by progressive dysfunction of CD8+tumor-infiltrating lymphocytes(TILs),...Cancer immunotherapy using immune-checkpoint inhibitors(ICIs)has revolutionized the field of cancer treatment;however,ICI efficacy is constrained by progressive dysfunction of CD8+tumor-infiltrating lymphocytes(TILs),which is termed T cell exhaustion.This process is driven by diverse extrinsic factors across heterogeneous tumor immune microenvironment(TIME).Simultaneously,tumorigenesis entails robust reshaping of the epigenetic landscape,potentially instigating T cell exhaustion.In this review,we summarize the epigenetic mechanisms governing tumor microenvironmental cues leading to T cell exhaustion,and discuss therapeutic potential of targeting epigenetic regulators for immunotherapies.Finally,we outline conceptual and technical advances in developing potential treatment paradigms involving immunostimulatory agents and epigenetic therapies.展开更多
Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSC...Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSCLC)and its molecular mechanism using mice bearing Lewis lung carcinoma cells.LRC significantly suppressed the growth of NSCLC.Besides,RNA sequencing of mice tumors and hematoxylin&eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes,specifically GZMB~+CD8~+T lymphocytes,in tumor tissues.The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways,suggesting that LRC exerted its effects through the PDL1/PD-1 pathway.Further experiments revealed that LRC interacted with PD-L1,blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells.Together,these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.展开更多
目的 使用孟德尔随机化(MR)分析方法探究近视与特定免疫细胞之间的因果关系。方法 对OPEN-GWAS数据库进行数据挖掘和分析,选取731种免疫细胞特征作为暴露因素,近视作为结局因素。设置显著阈值,筛选与免疫细胞及近视显著相关的单核苷酸...目的 使用孟德尔随机化(MR)分析方法探究近视与特定免疫细胞之间的因果关系。方法 对OPEN-GWAS数据库进行数据挖掘和分析,选取731种免疫细胞特征作为暴露因素,近视作为结局因素。设置显著阈值,筛选与免疫细胞及近视显著相关的单核苷酸多态性(SNP),并排除弱工具变量偏倚的影响。主要的分析方法是采用逆方差加权法(IVW),同时使用简单模式法、加权中位数法、加权模式法和MR-Egger回归进行数据分析。通过比值比和95%置信区间评估循环免疫细胞与近视的因果关系。对于符合假设的免疫细胞SNP,采用Cochran Q检验来评估异质性,并使用MR-Egger回归和MR-PRESSO法来排除SNP的水平多效性,利用留一法分析来评估显著结果是否由单个SNP影响。为了避免反向因果关系,本研究将近视作为暴露变量,免疫细胞表型为结果变量进行反向MR分析。此外,采用多变量MR分析(MVMR)评估这些免疫细胞对近视的因果和独立效应。结果 (1)两样本MR IVW法结果显示,Memory B cell AC(B细胞)和CD24+CD27+AC(B细胞)是近视发生的保护因素。Naive CD8br%CD8br(T细胞)、CD39+CD8br AC(T细胞)、CD25 on CD39+activated Treg(T细胞)、PDL-1 on CD14+CD16+monocyte(单核细胞)以及CD80 on myeloid DC(髓系树突状细胞)是近视发生的风险因素,且其余MR-Egger等方法结果与IVW方向一致。MR-Egger回归和MR-PRESSO分析表明,不存在水平多效性(P>0.05)。(2)双样本反向MR分析结果显示,近视与上述7种免疫细胞之间均无双向因果关系(均为P>0.05)。(3)在MVMR分析中,CD80 on myeloid DC与近视之间的显著因果关系在调整了潜在的混杂变量后依然稳健。结论 本研究通过遗传学手段,揭示了多种免疫表型与近视之间的复杂因果关系,展示了免疫系统与近视之间相互作用的复杂调控模式。展开更多
文摘The effects of dietary zinc on the immune organs and cellular immunity were investigated in the rats of zinc-deficient(ZD), zinc-excessive(ZE), paired feeding(PF) and ad libitus(AL) groups. The findings were as follows: (1) The weight of the thymus and spleen and the ratio with the body weight, the size of the cells,the production of thymic peptides and thymin activity were significantly lower in ZD and ZE groups than in PF and AL groups. (2) The total number of the cells in G_0/G_1 phase of T-and B-cells and bone marrow cells were significantly higher in ZD and ZF groups than in PF and AL groups while that of the cells in S and G_2/M phases were significantly lower in ZD and ZE groups than in PF and AL groups. (3) The cellular DNA, RNA and protein content in the thymus, spleen and bone marrow were significantly lower in ZD and ZE groups than in PF and AL groups.(4) The ￣3H-TdR incorporation rate of splenic T-and B-cells , IL-2 activity, plasma level of TNF and nitrogen oxide(NO) were significantly lower in ZD group than in PF group. (5) The leucocyte count of the perpheral blood,the percentage of lymphocytes, the bacteriocidal activity of phagocytes, and the phagocytic rate and index of abdominal phagocytes were significantly lower in ZD and ZE groups than in PF and AL groups. These findings indicate that an adequate amount of dietary zinc is essential for the development of immune organs and the promotion of cellular immunity while deficiency or excess of zinc is able to damage the immune function.
基金supported by the National Natural Science Foundation of China(82204634,82174047,81622051)the Zhejiang Provincial Natural Science Foundation of China(LQ22H280010)the Foundation of Zhejiang Chinese Medical University(2021ZR03).
文摘Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.
文摘Studied features of cellular and humoral factors of immune system and activation markers of lymphocytes at breast cancer patients.Analyzed biophysical parameters of lymphocyte superficial membranes of periphery blood of breast cancer patients.Features of immune system reaction were:expressed Т - cellular immunodeficiency,deficiency of CD4+Т-helpers/inducers against raised expression of СD8+Т-lymphocyte,suppression of immunoregulatory index,imbalance of immunity humoral link,activity of expression CD16 + and CD56 + on natural killers and rising of expression CD38 + and CD95 + on lymphocytes.Studying of biophysical parameters of lymphocytes superficial membranes has allowed to reveal statistically significant changes characterized by intensifying of electric field and rising ofmicroviscosity,obviously leading to disappearance or weakening of intercellular interactions.
基金This work was supported by the National Natural Science Foundation of China(82172511)the Natural Science Foundation of Jiangsu Province(BK20210068)+4 种基金the Sanming Project of Medicine in Shenzhen(SZSM201612078)the Health Shanghai Initiative Special Fund[Medical-Sports Integration(JKSHZX-2022-02)]the Top Talent Support Program for Young-and Middle-aged People of Wuxi Municipal Health Commission(HB2020003)the Mega-project of Wuxi Commission of Health(Z202216)the High-end Medical Expert Team of the 2019 Taihu Talent Plan(2019-THRCTD-1)
文摘Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.
基金supported by the National Natural Science Foundation of China(82273202,82370948,82072996,82170941)the Fundamental Research Funds for the Central Universities(2042022dx0003)+1 种基金the Hubei Province International Science and Technology Cooperation Project(2021EHB027)the National Key Research and Development Program(2022YFC2504200).
文摘Cancer immunotherapy using immune-checkpoint inhibitors(ICIs)has revolutionized the field of cancer treatment;however,ICI efficacy is constrained by progressive dysfunction of CD8+tumor-infiltrating lymphocytes(TILs),which is termed T cell exhaustion.This process is driven by diverse extrinsic factors across heterogeneous tumor immune microenvironment(TIME).Simultaneously,tumorigenesis entails robust reshaping of the epigenetic landscape,potentially instigating T cell exhaustion.In this review,we summarize the epigenetic mechanisms governing tumor microenvironmental cues leading to T cell exhaustion,and discuss therapeutic potential of targeting epigenetic regulators for immunotherapies.Finally,we outline conceptual and technical advances in developing potential treatment paradigms involving immunostimulatory agents and epigenetic therapies.
基金supported by Natural Science Foundation of Guangdong Province,China(2022A1515011575)National Natural Science Foundation of China,China(81873154)President Foundation of Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,China(1202103010)。
文摘Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSCLC)and its molecular mechanism using mice bearing Lewis lung carcinoma cells.LRC significantly suppressed the growth of NSCLC.Besides,RNA sequencing of mice tumors and hematoxylin&eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes,specifically GZMB~+CD8~+T lymphocytes,in tumor tissues.The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways,suggesting that LRC exerted its effects through the PDL1/PD-1 pathway.Further experiments revealed that LRC interacted with PD-L1,blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells.Together,these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.
文摘目的 使用孟德尔随机化(MR)分析方法探究近视与特定免疫细胞之间的因果关系。方法 对OPEN-GWAS数据库进行数据挖掘和分析,选取731种免疫细胞特征作为暴露因素,近视作为结局因素。设置显著阈值,筛选与免疫细胞及近视显著相关的单核苷酸多态性(SNP),并排除弱工具变量偏倚的影响。主要的分析方法是采用逆方差加权法(IVW),同时使用简单模式法、加权中位数法、加权模式法和MR-Egger回归进行数据分析。通过比值比和95%置信区间评估循环免疫细胞与近视的因果关系。对于符合假设的免疫细胞SNP,采用Cochran Q检验来评估异质性,并使用MR-Egger回归和MR-PRESSO法来排除SNP的水平多效性,利用留一法分析来评估显著结果是否由单个SNP影响。为了避免反向因果关系,本研究将近视作为暴露变量,免疫细胞表型为结果变量进行反向MR分析。此外,采用多变量MR分析(MVMR)评估这些免疫细胞对近视的因果和独立效应。结果 (1)两样本MR IVW法结果显示,Memory B cell AC(B细胞)和CD24+CD27+AC(B细胞)是近视发生的保护因素。Naive CD8br%CD8br(T细胞)、CD39+CD8br AC(T细胞)、CD25 on CD39+activated Treg(T细胞)、PDL-1 on CD14+CD16+monocyte(单核细胞)以及CD80 on myeloid DC(髓系树突状细胞)是近视发生的风险因素,且其余MR-Egger等方法结果与IVW方向一致。MR-Egger回归和MR-PRESSO分析表明,不存在水平多效性(P>0.05)。(2)双样本反向MR分析结果显示,近视与上述7种免疫细胞之间均无双向因果关系(均为P>0.05)。(3)在MVMR分析中,CD80 on myeloid DC与近视之间的显著因果关系在调整了潜在的混杂变量后依然稳健。结论 本研究通过遗传学手段,揭示了多种免疫表型与近视之间的复杂因果关系,展示了免疫系统与近视之间相互作用的复杂调控模式。
