Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early mar...Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.展开更多
Background: The absence of a safe and effective therapy for recurrent spontaneous abortion due to a maternofetal failure in immunological tolerance remains an intractable clinical obstacle for surgeons. Recently, trad...Background: The absence of a safe and effective therapy for recurrent spontaneous abortion due to a maternofetal failure in immunological tolerance remains an intractable clinical obstacle for surgeons. Recently, traditional Chinese medicine has become a feasible alternative for certain diseases, including recurrent spontaneous abortion. However, because of the complex composition of the traditional Chinese medicine formula, its action mechanism remains unclear. Methods: We selected two isolated active ingredients (RAMP and baicalin) from the traditional Chinese medicine formula and used an abortion-prone CBA/J × DBA/2 model to simulate human RSA and compared the changes in fetal resorption rate, Treg cell percentage, and relevant cytokines before and after combination therapy. In addition, The mechanisms were preliminarily discussed using in vitro differentiation models. Results: In CBA/J × DBA/2 abortion-prone mice, the combination therapy resulted in a lower embryo resorption rate compared to that obtained with individual delivery of either RAMP or baicalin, thereby playing an embryo-protective role through the increase in Treg cells for the maintenance of maternal-fetal immune tolerance. In in vitro primary cell differentiation experiments, the concentration of Treg cells significantly increased from 11% to 17.9% after the combination therapy compared to that of the single administration group. Conclusion: the synergistic effects of RAMP and baicalin were responsible for Treg differentiation. The present study provides a solid basis for improving the applicability of traditional Chinese herbs in the treatment of recurrent spontaneous abortion.展开更多
Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Per...Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.展开更多
Methylprednisolone pulse treatment is currently used fo r optic neuritis.It can speed visual recovery,but does not improve the ultimate visual outcomes.Recent studies have repo rted that miR-125 a-5 p has immunomodula...Methylprednisolone pulse treatment is currently used fo r optic neuritis.It can speed visual recovery,but does not improve the ultimate visual outcomes.Recent studies have repo rted that miR-125 a-5 p has immunomodulatory effects on autoimmune diseases.However,it remains unclear whether miR-125 a-5 p has effects on optic neuritis.In this study,we used adeno-associated virus to overexpress or silence miR-125 a-5 p in mice.We found that silencing miR-125 a-5 p increased the latency of visual evoked potential and aggravated inflammation of the optic nerve.Ove rexpression of miR-125 a-5 p suppressed inflammation of the optic nerve,protected retinal ganglion cells,and increased the percentage of Treg cells.Our findings show that miR-125 a-5 p exhibits anti-inflammatory effects through promoting the diffe rentiation of Treg cells.展开更多
BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is an innovative surgical approach for the treatment of massive hepatocellular carcinoma(HCC),the key to successful planned ...BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is an innovative surgical approach for the treatment of massive hepatocellular carcinoma(HCC),the key to successful planned stage 2 ALPPS is future liver remnant(FLR)volume growth,but the exact mechanism has not been elucidated.The correlation between regulatory T cells(Tregs)and postoperative FLR regeneration has not been reported.AIM To investigate the effect of CD4^(+)CD25^(+)Tregs on FLR regeneration after ALPPS.METHODS Clinical data and specimens were collected from 37 patients who developed massive HCC treated with ALPPS.Flow cytometry was performed to detect changes in the proportion of CD4^(+)CD25^(+)Tregs to CD4^(+)T cells in peripheral blood before and after ALPPS.To analyze the relationship between peripheral blood CD4^(+)CD25^(+)Treg proportion and clinicopathological information and liver volume.RESULTS The postoperative CD4^(+)CD25^(+)Treg proportion in stage 1 ALPPS was negatively correlated with the amount of proliferation volume,proliferation rate,and kinetic growth rate(KGR)of the FLR after stage 1 ALPPS.Patients with low Treg proportion had significantly higher KGR than those with high Treg proportion(P=0.006);patients with high Treg proportion had more severe postoperative pathological liver fibrosis than those with low Treg proportion(P=0.043).The area under the receiver operating characteristic curve between the percentage of Tregs and proliferation volume,proliferation rate,and KGR were all greater than 0.70.CONCLUSION CD4^(+)CD25^(+)Tregs in the peripheral blood of patients with massive HCC at stage 1 ALPPS were negatively correlated with indicators of FLR regeneration after stage 1 ALPPS and may influence the degree of fibrosis in patients’livers.Treg percentage was highly accurate in predicting the FLR regeneration after stage 1 ALPPS.展开更多
BACKGROUND Traditional Chinese medicine has used the drug Pien Tze Huang(PTH),a classic prescription,to treat autoimmune hepatitis(AIH).However,the precise mode of action is still unknown.AIM To investigate the mechan...BACKGROUND Traditional Chinese medicine has used the drug Pien Tze Huang(PTH),a classic prescription,to treat autoimmune hepatitis(AIH).However,the precise mode of action is still unknown.AIM To investigate the mechanism of PTH in an AIH mouse model by determining the changes in gut microbiota structure and memory regulatory T(mTreg)cells functional levels.METHODS Following induction of the AIH mouse model induced by Concanavalin A(Con A),prophylactic administration of PTH was given for 10 d.The levels of mTreg cells were measured by flow cytometry,and intestinal microbiota was analyzed by 16S rRNA analysis,while western blotting was used to identify activation of the toll-like receptor(TLR)2,TLR4/nuclear factor-κB(NF-κB),and CXCL16/CXCR6 signaling pathways.RESULTS In the liver of mice with AIH,PTH relieved the pathological damage and reduced the numbers of T helper type 17 cells and interferon-γ,tumor necrosis factor-alpha,interleukin(IL)-1β,IL-2,IL-6,and IL-21 expression.Simultaneously,PTH stimulated the abundance of helpful bacteria,promoted activation of the TLR2 signal,which may enhance Treg/mTreg cells quantity to produce IL-10,and suppressed activation of the TLR4/NF-κB and CXCL16/CXCR6 signaling pathways.CONCLUSION PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH,which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway.展开更多
目的探讨骨外膜素(Periostin)、Notch跨膜受体-1(Notch1)m RNA、维生素D(VitD)与自身免疫性甲状腺炎(AIT)淋巴细胞浸润程度、调节性T细胞/辅助性T细胞17(Treg/Th17)的相关性。方法选取2021年7月至2023年12月郑州大学第一附属医院收治的9...目的探讨骨外膜素(Periostin)、Notch跨膜受体-1(Notch1)m RNA、维生素D(VitD)与自身免疫性甲状腺炎(AIT)淋巴细胞浸润程度、调节性T细胞/辅助性T细胞17(Treg/Th17)的相关性。方法选取2021年7月至2023年12月郑州大学第一附属医院收治的92例AIT患者纳入AIT组,另选取同期50例无甲状腺疾病的健康人群纳入对照组。比较两组受检者的淋巴细胞浸润程度及抗体水平,采用Spearman、Pearson相关系数分析淋巴细胞浸润程度、Treg/Th17与甲状腺功能、抗体水平的相关性,比较两组受检者的Periostin、Notch1 m RNA、VitD及Treg/Th17,采用Pearson相关系数分析Periostin、Notch1 mRNA、VitD与淋巴细胞浸润程度及Treg/Th17的相关性。结果AIT组患者的CD3~+、CD3~+CD4~+、CD4~+CD25~+CD127~-、TgAb、TPOAb、TRAb水平及甲亢/亚临床甲亢、甲减/亚临床甲减患者占比明显高于对照组,差异均有统计学意义(P<0.05);Pearson相关系数分析结果显示,CD3~+(r=0.579、0.602、0.563)、CD3+CD4+(r=0.612、0.637、0.606)、CD~4+CD25~+CD127~-(r=0.655、0.643、0.687)与TgAb、TPOAb、TRAb呈正相关(P<0.05);AIT组患者的Periostin、Notch1 m RNA分别为(4.27±1.40)μg/L、1.73±0.56,明显高于对照组的(2.86±0.49)μg/L、1.02±0.14,VitD、Treg/Th17分别为(17.82±5.09)ng/mL、2.82±0.97,明显低于对照组的(22.30±3.76)ng/mL、12.36±2.03,差异均有统计学意义(P<0.05);Pearson相关系数分析结果显示,Periostin(r=0.792、0.811、0.737)、Notch1 mRNA(r=0.812、0.775、0.792)与CD3+、CD3+CD4+、CD4+CD25+CD127-呈正相关(P<0.05),VitD(r=-0.687、-0.753、-0.799)与之呈负相关(P<0.05),且Periostin(r=-0.823)、Notch1 m RNA(r=-0.772)与Treg/Th17呈负相关(P<0.05),VitD(r=0.745)与之呈正相关(P<0.05)。结论Periostin、Notch1 mRNA在AIT患者血清中表达上调,VitD表达下调,各指标与AIT淋巴细胞浸润程度及Treg/Th17均具有一定相关性,可为临床判断病情提供参考,并对后续临床治疗具有一定指导价值。展开更多
目的探讨慢性阻塞性肺疾病急性加重期(acute exacerhation of chronic obstructive pulmonary disease,AECOPD)患者治疗前后Th17/Treg免疫平衡、呼出气一氧化氮(fraction of exhaled nitric oxide,FeNO)水平变化及对预后的影响。方法选...目的探讨慢性阻塞性肺疾病急性加重期(acute exacerhation of chronic obstructive pulmonary disease,AECOPD)患者治疗前后Th17/Treg免疫平衡、呼出气一氧化氮(fraction of exhaled nitric oxide,FeNO)水平变化及对预后的影响。方法选取AECOPD患者126例,采用肺功能检测仪测定第1秒用力呼气量(forced expiratory volume in one second,FEV1)、第1秒用力呼气量占预计值百分比(FEV1%)、用力肺活量(forced vital capacity,FVC)、用力肺活量占预计值百分比(FVC%)、第1秒用力呼气量占用力肺活量的百分比(FEV1/FVC)。并使用一氧化氮测定仪检测FeNO水平,采用全身炎性反应综合征(systemic inflammaton response syndrome,SIRS)评分进行评分,采用流式细胞仪检测血清辅助性T细胞17(T help 17cells,Th17)、调节性T细胞(T Regulatory cells,Treg)水平,比较治疗前后患者肺功能指标、FeNO水平、SIRS评分、Th17/Treg水平等指标变化情况。结果治疗3个月后,AECOPD患者FEV1%、FEV1/FVC、Th17、Th17/Treg水平显著高于治疗前,FeNO、血清Treg水平、SIRS评分显著低于治疗前(P<0.05)。126例AECOPD患者治疗3个月后存活94例(74.60%);死亡32例(25.40%)。存活组FEV1%、FEV1/FVC、Treg水平显著高于死亡组,FeNO、Th17、Th17/Treg及SIRS评分显著低于死亡组(P<0.05)。多因素Logistic回归分析结果显示,治疗前FEV1%、FEV1/FVC、Treg是AECOPD患者预后的危险因素(P<0.05);FeNO、Th17、Th17/Treg、SIRS评分是AECOPD患者预后的保护因素(P<0.05)。结论AECOPD患者治疗后肺功能提高,Th17/Treg、FeNO降低,肺功能、Th17/Treg免疫平衡、FeNO水平对AECOPD患者疗效评估及预后判断具有重要意义。展开更多
类风湿关节炎(rheumatoid arthritis,RA)是全身性、持续性、自身免疫性疾病,其病理机制涉及多种免疫细胞,尤其是T淋巴细胞。辅助性T细胞17(relper T cell 17,Th17)和调节性T细胞(regulatory T cell,Treg)是构成免疫系统的关键元素,在维...类风湿关节炎(rheumatoid arthritis,RA)是全身性、持续性、自身免疫性疾病,其病理机制涉及多种免疫细胞,尤其是T淋巴细胞。辅助性T细胞17(relper T cell 17,Th17)和调节性T细胞(regulatory T cell,Treg)是构成免疫系统的关键元素,在维持免疫稳态方面起着重要的作用。对单味中药及其有效成分、中药复方、中成药基于Th17/Treg平衡治疗RA的研究进展进行概括,为RA的临床治疗提供理论指导,为了解RA的发病机制提供新的思路。展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
基金funded by the Central Hessen Research Campus,Flexi Fund,Project No.20121_1_1.
文摘Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.
基金the National Natural Science Foundation of China(81973221)National Natural Science Foundation for Young Scientists of China(81603647)+2 种基金the Women and Children Health Talent Project of Jiangsu Province(FRC201785)the Chinese Clinical Medicine Innovation Center of Obstetrics,Gynecology,and Reproduction in Jiangsu Province(ZX202102)the Women and Children Health Science Foundation of Jiangsu Province(F202206).
文摘Background: The absence of a safe and effective therapy for recurrent spontaneous abortion due to a maternofetal failure in immunological tolerance remains an intractable clinical obstacle for surgeons. Recently, traditional Chinese medicine has become a feasible alternative for certain diseases, including recurrent spontaneous abortion. However, because of the complex composition of the traditional Chinese medicine formula, its action mechanism remains unclear. Methods: We selected two isolated active ingredients (RAMP and baicalin) from the traditional Chinese medicine formula and used an abortion-prone CBA/J × DBA/2 model to simulate human RSA and compared the changes in fetal resorption rate, Treg cell percentage, and relevant cytokines before and after combination therapy. In addition, The mechanisms were preliminarily discussed using in vitro differentiation models. Results: In CBA/J × DBA/2 abortion-prone mice, the combination therapy resulted in a lower embryo resorption rate compared to that obtained with individual delivery of either RAMP or baicalin, thereby playing an embryo-protective role through the increase in Treg cells for the maintenance of maternal-fetal immune tolerance. In in vitro primary cell differentiation experiments, the concentration of Treg cells significantly increased from 11% to 17.9% after the combination therapy compared to that of the single administration group. Conclusion: the synergistic effects of RAMP and baicalin were responsible for Treg differentiation. The present study provides a solid basis for improving the applicability of traditional Chinese herbs in the treatment of recurrent spontaneous abortion.
基金supported by grants from the National Natural Science Foundation of China(No.82271755,No.81871230)Peking University People's Hospital Scientific Research Development Funds(RZ 2022-06).
文摘Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.
基金supported by the National Natural Science Foundation of China,No.81560162the Guangxi Natural Science Foundation of China,No.2018GXNSFAA050052(both YD)。
文摘Methylprednisolone pulse treatment is currently used fo r optic neuritis.It can speed visual recovery,but does not improve the ultimate visual outcomes.Recent studies have repo rted that miR-125 a-5 p has immunomodulatory effects on autoimmune diseases.However,it remains unclear whether miR-125 a-5 p has effects on optic neuritis.In this study,we used adeno-associated virus to overexpress or silence miR-125 a-5 p in mice.We found that silencing miR-125 a-5 p increased the latency of visual evoked potential and aggravated inflammation of the optic nerve.Ove rexpression of miR-125 a-5 p suppressed inflammation of the optic nerve,protected retinal ganglion cells,and increased the percentage of Treg cells.Our findings show that miR-125 a-5 p exhibits anti-inflammatory effects through promoting the diffe rentiation of Treg cells.
基金the National Natural Science Foundation of China,No.8190111624Guangxi Natural Science Foundation of China,No.2018JJB140382Guangxi University Young and Middle-Aged Teachers’Basic Scientific Research Ability Improvement Project,No.2019KY0123.
文摘BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is an innovative surgical approach for the treatment of massive hepatocellular carcinoma(HCC),the key to successful planned stage 2 ALPPS is future liver remnant(FLR)volume growth,but the exact mechanism has not been elucidated.The correlation between regulatory T cells(Tregs)and postoperative FLR regeneration has not been reported.AIM To investigate the effect of CD4^(+)CD25^(+)Tregs on FLR regeneration after ALPPS.METHODS Clinical data and specimens were collected from 37 patients who developed massive HCC treated with ALPPS.Flow cytometry was performed to detect changes in the proportion of CD4^(+)CD25^(+)Tregs to CD4^(+)T cells in peripheral blood before and after ALPPS.To analyze the relationship between peripheral blood CD4^(+)CD25^(+)Treg proportion and clinicopathological information and liver volume.RESULTS The postoperative CD4^(+)CD25^(+)Treg proportion in stage 1 ALPPS was negatively correlated with the amount of proliferation volume,proliferation rate,and kinetic growth rate(KGR)of the FLR after stage 1 ALPPS.Patients with low Treg proportion had significantly higher KGR than those with high Treg proportion(P=0.006);patients with high Treg proportion had more severe postoperative pathological liver fibrosis than those with low Treg proportion(P=0.043).The area under the receiver operating characteristic curve between the percentage of Tregs and proliferation volume,proliferation rate,and KGR were all greater than 0.70.CONCLUSION CD4^(+)CD25^(+)Tregs in the peripheral blood of patients with massive HCC at stage 1 ALPPS were negatively correlated with indicators of FLR regeneration after stage 1 ALPPS and may influence the degree of fibrosis in patients’livers.Treg percentage was highly accurate in predicting the FLR regeneration after stage 1 ALPPS.
基金Supported by the National Natural Science Foundation of China,No.81603402,82060798,81860791the Special Fund Project for Graduate Innovation of Jiangxi University of Chinese Medicine,No.JZYC22S77+3 种基金a Special Fund Project for Graduate Innovation of Jiangxi Province,No.YC2022-s840,YC2022-B188Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program,No.CXTD22008the Young and Middle-aged Backbone Talent Project of Jiangxi Administration of Traditional Chinese Medicine,No.[2020]05Young Qhuang Scholars support Project of National Administration of Traditional Chinese Medicine,No.[2022]256.
文摘BACKGROUND Traditional Chinese medicine has used the drug Pien Tze Huang(PTH),a classic prescription,to treat autoimmune hepatitis(AIH).However,the precise mode of action is still unknown.AIM To investigate the mechanism of PTH in an AIH mouse model by determining the changes in gut microbiota structure and memory regulatory T(mTreg)cells functional levels.METHODS Following induction of the AIH mouse model induced by Concanavalin A(Con A),prophylactic administration of PTH was given for 10 d.The levels of mTreg cells were measured by flow cytometry,and intestinal microbiota was analyzed by 16S rRNA analysis,while western blotting was used to identify activation of the toll-like receptor(TLR)2,TLR4/nuclear factor-κB(NF-κB),and CXCL16/CXCR6 signaling pathways.RESULTS In the liver of mice with AIH,PTH relieved the pathological damage and reduced the numbers of T helper type 17 cells and interferon-γ,tumor necrosis factor-alpha,interleukin(IL)-1β,IL-2,IL-6,and IL-21 expression.Simultaneously,PTH stimulated the abundance of helpful bacteria,promoted activation of the TLR2 signal,which may enhance Treg/mTreg cells quantity to produce IL-10,and suppressed activation of the TLR4/NF-κB and CXCL16/CXCR6 signaling pathways.CONCLUSION PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH,which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway.
文摘目的探讨骨外膜素(Periostin)、Notch跨膜受体-1(Notch1)m RNA、维生素D(VitD)与自身免疫性甲状腺炎(AIT)淋巴细胞浸润程度、调节性T细胞/辅助性T细胞17(Treg/Th17)的相关性。方法选取2021年7月至2023年12月郑州大学第一附属医院收治的92例AIT患者纳入AIT组,另选取同期50例无甲状腺疾病的健康人群纳入对照组。比较两组受检者的淋巴细胞浸润程度及抗体水平,采用Spearman、Pearson相关系数分析淋巴细胞浸润程度、Treg/Th17与甲状腺功能、抗体水平的相关性,比较两组受检者的Periostin、Notch1 m RNA、VitD及Treg/Th17,采用Pearson相关系数分析Periostin、Notch1 mRNA、VitD与淋巴细胞浸润程度及Treg/Th17的相关性。结果AIT组患者的CD3~+、CD3~+CD4~+、CD4~+CD25~+CD127~-、TgAb、TPOAb、TRAb水平及甲亢/亚临床甲亢、甲减/亚临床甲减患者占比明显高于对照组,差异均有统计学意义(P<0.05);Pearson相关系数分析结果显示,CD3~+(r=0.579、0.602、0.563)、CD3+CD4+(r=0.612、0.637、0.606)、CD~4+CD25~+CD127~-(r=0.655、0.643、0.687)与TgAb、TPOAb、TRAb呈正相关(P<0.05);AIT组患者的Periostin、Notch1 m RNA分别为(4.27±1.40)μg/L、1.73±0.56,明显高于对照组的(2.86±0.49)μg/L、1.02±0.14,VitD、Treg/Th17分别为(17.82±5.09)ng/mL、2.82±0.97,明显低于对照组的(22.30±3.76)ng/mL、12.36±2.03,差异均有统计学意义(P<0.05);Pearson相关系数分析结果显示,Periostin(r=0.792、0.811、0.737)、Notch1 mRNA(r=0.812、0.775、0.792)与CD3+、CD3+CD4+、CD4+CD25+CD127-呈正相关(P<0.05),VitD(r=-0.687、-0.753、-0.799)与之呈负相关(P<0.05),且Periostin(r=-0.823)、Notch1 m RNA(r=-0.772)与Treg/Th17呈负相关(P<0.05),VitD(r=0.745)与之呈正相关(P<0.05)。结论Periostin、Notch1 mRNA在AIT患者血清中表达上调,VitD表达下调,各指标与AIT淋巴细胞浸润程度及Treg/Th17均具有一定相关性,可为临床判断病情提供参考,并对后续临床治疗具有一定指导价值。
文摘目的探讨慢性阻塞性肺疾病急性加重期(acute exacerhation of chronic obstructive pulmonary disease,AECOPD)患者治疗前后Th17/Treg免疫平衡、呼出气一氧化氮(fraction of exhaled nitric oxide,FeNO)水平变化及对预后的影响。方法选取AECOPD患者126例,采用肺功能检测仪测定第1秒用力呼气量(forced expiratory volume in one second,FEV1)、第1秒用力呼气量占预计值百分比(FEV1%)、用力肺活量(forced vital capacity,FVC)、用力肺活量占预计值百分比(FVC%)、第1秒用力呼气量占用力肺活量的百分比(FEV1/FVC)。并使用一氧化氮测定仪检测FeNO水平,采用全身炎性反应综合征(systemic inflammaton response syndrome,SIRS)评分进行评分,采用流式细胞仪检测血清辅助性T细胞17(T help 17cells,Th17)、调节性T细胞(T Regulatory cells,Treg)水平,比较治疗前后患者肺功能指标、FeNO水平、SIRS评分、Th17/Treg水平等指标变化情况。结果治疗3个月后,AECOPD患者FEV1%、FEV1/FVC、Th17、Th17/Treg水平显著高于治疗前,FeNO、血清Treg水平、SIRS评分显著低于治疗前(P<0.05)。126例AECOPD患者治疗3个月后存活94例(74.60%);死亡32例(25.40%)。存活组FEV1%、FEV1/FVC、Treg水平显著高于死亡组,FeNO、Th17、Th17/Treg及SIRS评分显著低于死亡组(P<0.05)。多因素Logistic回归分析结果显示,治疗前FEV1%、FEV1/FVC、Treg是AECOPD患者预后的危险因素(P<0.05);FeNO、Th17、Th17/Treg、SIRS评分是AECOPD患者预后的保护因素(P<0.05)。结论AECOPD患者治疗后肺功能提高,Th17/Treg、FeNO降低,肺功能、Th17/Treg免疫平衡、FeNO水平对AECOPD患者疗效评估及预后判断具有重要意义。
文摘类风湿关节炎(rheumatoid arthritis,RA)是全身性、持续性、自身免疫性疾病,其病理机制涉及多种免疫细胞,尤其是T淋巴细胞。辅助性T细胞17(relper T cell 17,Th17)和调节性T细胞(regulatory T cell,Treg)是构成免疫系统的关键元素,在维持免疫稳态方面起着重要的作用。对单味中药及其有效成分、中药复方、中成药基于Th17/Treg平衡治疗RA的研究进展进行概括,为RA的临床治疗提供理论指导,为了解RA的发病机制提供新的思路。