Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to ex...Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to examine the correlation of the mRNA levels between PD and BTLA in NSCLC.Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8^+T cells andγδ+T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals.We compared the expression of PD1 and BTLA on the surfaces ofγδ+T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid.The correlations of PD1 and BTLA,as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform.Results The frequency of PD1 on the surfaces of CD8^+T cells was significantly higher than that of theγδT cells in both healthy controls(t=2.324,P=0.024)and NSCLC patients(t=2.498,P=0.015).The frequency of PD1 on CD8^+T cells,rather than onγδ+T cells,was significantly upregulated in advanced NSCLC patients compared with that in healthy controls(t=4.829,P<0.001).The PD1+BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients(t=2.422,P=0.0185).No differences in percentage of PD1+γδ+and BTLA+γδ+T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment.PD1 was positively correlated with BTLA in both lung adenocarcinoma(r=0.54;P<0.05)and lung squamous cell carcinoma(r=0.78;P<0.05).Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8^+T cells andγδT cells in advanced NSCLC,suggesting that these molecules were involved in regulating the inactivation of CD8^+T cells andγδ+T cells,immune escape and tumor invasion.展开更多
乙型肝炎病毒(hepatitis B virus,HBV)X蛋白(HBx)对肝癌的发生发展具有十分重要的作用.我们前期研究发现,HBx突变体(HBxΔ127)与肝癌的增殖和迁移有密切的关系.钙蛋白酶小亚基1(calpain small subunit 1,Capn4)具有促进细胞迁移、增殖...乙型肝炎病毒(hepatitis B virus,HBV)X蛋白(HBx)对肝癌的发生发展具有十分重要的作用.我们前期研究发现,HBx突变体(HBxΔ127)与肝癌的增殖和迁移有密切的关系.钙蛋白酶小亚基1(calpain small subunit 1,Capn4)具有促进细胞迁移、增殖和分化的作用.本研究对HBx突变体(HBxΔ127)促进肝癌细胞迁移的分子机制进行了研究.实验结果显示,HBxΔ127可明显激活Capn4的启动子活性和上调Capn4蛋白表达.应用ERK抑制剂PD98059作用肝癌细胞后,可明显抑制HBxΔ127对Capn4的上调作用,提示HBxΔ127可通过磷酸化ERK1/2(p-ERK1/2)上调Capn4.应用伤口愈合实验进一步证实,HBxΔ127促进肝癌细胞迁移的作用与Capn4和p-ERK1/2有关.本研究结果表明,HBxΔ127促进肝癌细胞迁移的作用是通过p-ERK1/2上调Capn4实现的.这一发现对进一步揭示HBx突变体HBxΔ127促进肝癌细胞转移的分子机制具有重要意义.展开更多
The effect of the administration of large amounts of green tea polyphenols is a matter of controversy. We explored whether a polyphenol mixture from a concentrated green tea extract (Polyphenon 60) could alter the eff...The effect of the administration of large amounts of green tea polyphenols is a matter of controversy. We explored whether a polyphenol mixture from a concentrated green tea extract (Polyphenon 60) could alter the effects on mice of the type 2 (two chains) ribosome-inactivating protein nigrin b isolated from Sambucus nigra L. Nigrin b triggers specific reversible toxic effects on the mouse intestines featured by apoptosis of mice Lieberkühn crypt cells upon parenteral administration of sub-lethal amounts. Independent administration to mice of 30 mg/kg body weight of Polyphenon 60 by oral gavage or 10 mg/kg body weight of nigrin b administered via the intraperitoneal route (i.p.) did not affect survival. In contrast, the simultaneous treatment greatly enhanced nigrin b toxicity leading to the death of some animals. The histological analysis revealed that the most serious injury was inflicted on the small intestine crypts, which disappeared, and on the liver, which evidenced hepatotoxicity showing haemorrhagic areas. These findings raise concerns about the abuse of high concentrations of green tea polyphenols especially when the intestinal mucosa is damaged, for instance by toxins or therapeutic drugs.展开更多
基金Fund supported by the Healthcare Technology Plan of Zhejiang Provincial Health Bureau(No.2016KYB292)the Technology Plan of Science and Technology Bureau of Jiaxing,Zhejiang province(No.2016AY23054)~~
文摘Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to examine the correlation of the mRNA levels between PD and BTLA in NSCLC.Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8^+T cells andγδ+T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals.We compared the expression of PD1 and BTLA on the surfaces ofγδ+T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid.The correlations of PD1 and BTLA,as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform.Results The frequency of PD1 on the surfaces of CD8^+T cells was significantly higher than that of theγδT cells in both healthy controls(t=2.324,P=0.024)and NSCLC patients(t=2.498,P=0.015).The frequency of PD1 on CD8^+T cells,rather than onγδ+T cells,was significantly upregulated in advanced NSCLC patients compared with that in healthy controls(t=4.829,P<0.001).The PD1+BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients(t=2.422,P=0.0185).No differences in percentage of PD1+γδ+and BTLA+γδ+T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment.PD1 was positively correlated with BTLA in both lung adenocarcinoma(r=0.54;P<0.05)and lung squamous cell carcinoma(r=0.78;P<0.05).Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8^+T cells andγδT cells in advanced NSCLC,suggesting that these molecules were involved in regulating the inactivation of CD8^+T cells andγδ+T cells,immune escape and tumor invasion.
文摘乙型肝炎病毒(hepatitis B virus,HBV)X蛋白(HBx)对肝癌的发生发展具有十分重要的作用.我们前期研究发现,HBx突变体(HBxΔ127)与肝癌的增殖和迁移有密切的关系.钙蛋白酶小亚基1(calpain small subunit 1,Capn4)具有促进细胞迁移、增殖和分化的作用.本研究对HBx突变体(HBxΔ127)促进肝癌细胞迁移的分子机制进行了研究.实验结果显示,HBxΔ127可明显激活Capn4的启动子活性和上调Capn4蛋白表达.应用ERK抑制剂PD98059作用肝癌细胞后,可明显抑制HBxΔ127对Capn4的上调作用,提示HBxΔ127可通过磷酸化ERK1/2(p-ERK1/2)上调Capn4.应用伤口愈合实验进一步证实,HBxΔ127促进肝癌细胞迁移的作用与Capn4和p-ERK1/2有关.本研究结果表明,HBxΔ127促进肝癌细胞迁移的作用是通过p-ERK1/2上调Capn4实现的.这一发现对进一步揭示HBx突变体HBxΔ127促进肝癌细胞转移的分子机制具有重要意义.
文摘The effect of the administration of large amounts of green tea polyphenols is a matter of controversy. We explored whether a polyphenol mixture from a concentrated green tea extract (Polyphenon 60) could alter the effects on mice of the type 2 (two chains) ribosome-inactivating protein nigrin b isolated from Sambucus nigra L. Nigrin b triggers specific reversible toxic effects on the mouse intestines featured by apoptosis of mice Lieberkühn crypt cells upon parenteral administration of sub-lethal amounts. Independent administration to mice of 30 mg/kg body weight of Polyphenon 60 by oral gavage or 10 mg/kg body weight of nigrin b administered via the intraperitoneal route (i.p.) did not affect survival. In contrast, the simultaneous treatment greatly enhanced nigrin b toxicity leading to the death of some animals. The histological analysis revealed that the most serious injury was inflicted on the small intestine crypts, which disappeared, and on the liver, which evidenced hepatotoxicity showing haemorrhagic areas. These findings raise concerns about the abuse of high concentrations of green tea polyphenols especially when the intestinal mucosa is damaged, for instance by toxins or therapeutic drugs.
