Heart failure （HF） is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide. Numerous studies have demonstrated that frequencies of CD4＋CD25＋Foxp3＋ regulatory T cells ...Heart failure （HF） is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide. Numerous studies have demonstrated that frequencies of CD4＋CD25＋Foxp3＋ regulatory T cells （Tregs） are reduced in HF patients and properly expanding Tregs attenuates HF progression. Histone deacetylase （HDAC） 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases. Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs. Thus, we aim to investigate the expression of HDAC 9 in patients with chronic heart failure （CHF） and the relationship among HDAC9, Tregs and CHF. Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients. Patients with CHF were divided into two groups by heart function grade of New York Heart Association （NYHA）, we found that the HDAC9 mRNA expression level in NYHA grade Ⅱ -Ⅲ group were lower than that in NYHA grade IV group. More importantly, the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction （LVEF）, whereas positively correlated to larger left ventricular end-diastolic dimension （LVEDD） and B-type natriuretic peptide （BNP） in patients with CHF. The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF. Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.展开更多
Objective: To determine the effect of cis-9, trans-1 1-conjugated linoleic acid on the cell cycle of mammary cancer cells (MCF-7) and the possible mechanism of the inhibitory effect of c9,t11-CLA. Methods: Using cell ...Objective: To determine the effect of cis-9, trans-1 1-conjugated linoleic acid on the cell cycle of mammary cancer cells (MCF-7) and the possible mechanism of the inhibitory effect of c9,t11-CLA. Methods: Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B1, D1, p16ink4a and p21cip/waf1 of MCF-7 cells at various c9,t11-CLA concentrations (25μM, 50μM, 100μM and 200μM), at 24h and 48h. 96% ethand was used as negative control. Results: The cell growth and DNA synthesis of MCF-7 cells were inhibited by c9,t11-CLA. After treatment with various doses of c9,t11-CLA mentioned above for 8 days, the inhibition frequency was 27.18%, 35.43%, 91.05%, and 92.86%, respectively. Inhibitory effect of c9,t11-CLA on DNA synthesis (except for 25μM, 24h) was demonstrated by significantly less incorporation of 3H-TdR than the negative control (P<0.05 and P<0.01). To further investigate the influence of the cell cycle progression, we found that c9,t11-CLA may arrest the cell cycle of MCF-7 cells. Immunocytochemical staining demonstrated that incubation with different concentration of c9,t11-CLA at various times significantly decreased the expression of PCNA, Cyclin A, B1, D1 in MCF-7 cells compared to the negative control (P<0.01), whereas the expression of p16ink4a and p21cip/waf1, cyclin-dependent kinases inhibitors (CDKI), were increased. Conclusions: The cell growth and proliferation of MCF-7 cells is inhibited by c9,t11-CLA via blocking cell cycle, accompanying reduced expression of cyclin A, B1, D1 and enhanced expression of CDKI (p16ink4a and p21cip/waf1).展开更多
Chimeric antigen receptor T(CAR-T)cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia(ALL),lymphoma and multiple myeloma.However,treatment-related toxicitie...Chimeric antigen receptor T(CAR-T)cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia(ALL),lymphoma and multiple myeloma.However,treatment-related toxicities such as cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)have become significant hurdles to CAR-T treatment.Multiple strategies were established to alter the CAR structure on the genomic level to improve efficacy and reduce toxicities.Recently,the innovative gene-editing technology-clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease9(Cas9)system,which particularly exhibits preponderance in knock-in and knockout at specific sites,is widely utilized to manufacture CAR-T products.The application of CRISPR/Cas9 to CAR-T cell therapy has shown promising clinical results with minimal toxicity.In this review,we summarized the past achievements of CRISPR/Cas9 in CAR-T therapy and focused on the potential CAR-T targets.展开更多
The interaction between some chemokines with tumoral and stromal cells can influence tumor progression. CXCL9, a monokine induced by interferon gamma (MIG), targets lymphocytes.The aim of our study was to identify and...The interaction between some chemokines with tumoral and stromal cells can influence tumor progression. CXCL9, a monokine induced by interferon gamma (MIG), targets lymphocytes.The aim of our study was to identify and quantify CD4+ and CD8+ T cells in the stroma of human breast cancer and correlate them with the presence of MIG/CXCL9. In 58 specimens of human breast carcinoma and 10 normal breast tissue from mammoplasty surgery, immunohistochemistry and ELISA methods were performed. The number of CD4+ and CD8+ T cells in breast cancer tissue was significantly increased compared with normal breast tissue with a clear predominance of CD8+ T cells. MIG/CXCL9 levels were significantly elevated respect normal breast tissue. This chemokine correlated with the number of CD8+ T cells only in non-metastatic tumors. These data suggest that MIG targets cytotoxic T cells. Their recruitment into breast carcinoma can play a critical role in malignant progression, inhibiting the production of metastasis.展开更多
Due to continuous scaling of CMOS, stability is a prime concerned for CMOS SRAM memory cells. As scaling will increase the packing density but at the same time it is affecting the stability which leads to write failur...Due to continuous scaling of CMOS, stability is a prime concerned for CMOS SRAM memory cells. As scaling will increase the packing density but at the same time it is affecting the stability which leads to write failures and read disturbs of the conventional 6T SRAM cell. To increase the stability of the cell various SRAM cell topologies has been introduced, 8T SRAM is one of them but it has its limitation like read disturbance. In this paper we have analyzed a novel PP based 9T SRAM at 45 nm technology. Cell which has 33% increased SVNM (Static Voltage Noise Margin) from 6T and also 22%.reduced leakage power. N curve analysis has been done to find the various stability factors. As compared to the 10T SRAM cell it is more area efficient.展开更多
目的:探究chemerin对银屑病患者外周血辅助性T淋巴细胞9(helper T cells 9,Th9)/调节性T淋巴细胞(regulatory T cells,Treg)免疫平衡的调节作用及其潜在的机制。方法:选取25例银屑病患者和20例健康志愿者,采用磁珠分离法分离出受试者外...目的:探究chemerin对银屑病患者外周血辅助性T淋巴细胞9(helper T cells 9,Th9)/调节性T淋巴细胞(regulatory T cells,Treg)免疫平衡的调节作用及其潜在的机制。方法:选取25例银屑病患者和20例健康志愿者,采用磁珠分离法分离出受试者外周血中CD4+T细胞,行实时RT-PCR和ELISA检测细胞中chemerin和其受体chemR23的表达;用不同浓度的chemerin(50,100,150,200 ng/mL)分别处理从健康志愿者外周血分离得到的CD4+T细胞,行MT T比色法检测细胞活力以筛选最适浓度;采用ELISA检测炎性细胞因子水平;行流式细胞术检测Th9和Treg细胞数。结果:与对照相比,银屑病患者外周血中chemerin和chemR23的表达均显著增加,T h 9/Treg比例明显上升(均P<0.05);选取最适浓度150 ng/mL的chemerin处理CD4+T细胞后,细胞中白细胞介素(IL)-6,IL-9和IL-17的水平均显著增加,Th9/Treg比例明显上升(均P<0.05),而chemR23沉默可反转chemerin对CD4+T细胞的上述作用(均P<0.05)。结论:Chemerin通过chemR23调节银屑病患者外周血CD4+T淋巴细胞中的T h 9/Treg细胞免疫平衡。展开更多
文摘Heart failure （HF） is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide. Numerous studies have demonstrated that frequencies of CD4＋CD25＋Foxp3＋ regulatory T cells （Tregs） are reduced in HF patients and properly expanding Tregs attenuates HF progression. Histone deacetylase （HDAC） 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases. Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs. Thus, we aim to investigate the expression of HDAC 9 in patients with chronic heart failure （CHF） and the relationship among HDAC9, Tregs and CHF. Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients. Patients with CHF were divided into two groups by heart function grade of New York Heart Association （NYHA）, we found that the HDAC9 mRNA expression level in NYHA grade Ⅱ -Ⅲ group were lower than that in NYHA grade IV group. More importantly, the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction （LVEF）, whereas positively correlated to larger left ventricular end-diastolic dimension （LVEDD） and B-type natriuretic peptide （BNP） in patients with CHF. The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF. Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.
基金This work was supported by the National Natural Science Foundation of China(No.39870661). Phone: (0086-451)-3641309 Fax: (0086-451)-3641253
文摘Objective: To determine the effect of cis-9, trans-1 1-conjugated linoleic acid on the cell cycle of mammary cancer cells (MCF-7) and the possible mechanism of the inhibitory effect of c9,t11-CLA. Methods: Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B1, D1, p16ink4a and p21cip/waf1 of MCF-7 cells at various c9,t11-CLA concentrations (25μM, 50μM, 100μM and 200μM), at 24h and 48h. 96% ethand was used as negative control. Results: The cell growth and DNA synthesis of MCF-7 cells were inhibited by c9,t11-CLA. After treatment with various doses of c9,t11-CLA mentioned above for 8 days, the inhibition frequency was 27.18%, 35.43%, 91.05%, and 92.86%, respectively. Inhibitory effect of c9,t11-CLA on DNA synthesis (except for 25μM, 24h) was demonstrated by significantly less incorporation of 3H-TdR than the negative control (P<0.05 and P<0.01). To further investigate the influence of the cell cycle progression, we found that c9,t11-CLA may arrest the cell cycle of MCF-7 cells. Immunocytochemical staining demonstrated that incubation with different concentration of c9,t11-CLA at various times significantly decreased the expression of PCNA, Cyclin A, B1, D1 in MCF-7 cells compared to the negative control (P<0.01), whereas the expression of p16ink4a and p21cip/waf1, cyclin-dependent kinases inhibitors (CDKI), were increased. Conclusions: The cell growth and proliferation of MCF-7 cells is inhibited by c9,t11-CLA via blocking cell cycle, accompanying reduced expression of cyclin A, B1, D1 and enhanced expression of CDKI (p16ink4a and p21cip/waf1).
基金the National Natural Science Foundation of China(No.81230014,No.81470341,No.81520108002 and No.81500157)the Key Project of Science and Technology Department of Zhejiang Province(No.2018C03016-2)the Key Research and Development Program of Zhejiang Province(No.2019C03016).
文摘Chimeric antigen receptor T(CAR-T)cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia(ALL),lymphoma and multiple myeloma.However,treatment-related toxicities such as cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)have become significant hurdles to CAR-T treatment.Multiple strategies were established to alter the CAR structure on the genomic level to improve efficacy and reduce toxicities.Recently,the innovative gene-editing technology-clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease9(Cas9)system,which particularly exhibits preponderance in knock-in and knockout at specific sites,is widely utilized to manufacture CAR-T products.The application of CRISPR/Cas9 to CAR-T cell therapy has shown promising clinical results with minimal toxicity.In this review,we summarized the past achievements of CRISPR/Cas9 in CAR-T therapy and focused on the potential CAR-T targets.
文摘The interaction between some chemokines with tumoral and stromal cells can influence tumor progression. CXCL9, a monokine induced by interferon gamma (MIG), targets lymphocytes.The aim of our study was to identify and quantify CD4+ and CD8+ T cells in the stroma of human breast cancer and correlate them with the presence of MIG/CXCL9. In 58 specimens of human breast carcinoma and 10 normal breast tissue from mammoplasty surgery, immunohistochemistry and ELISA methods were performed. The number of CD4+ and CD8+ T cells in breast cancer tissue was significantly increased compared with normal breast tissue with a clear predominance of CD8+ T cells. MIG/CXCL9 levels were significantly elevated respect normal breast tissue. This chemokine correlated with the number of CD8+ T cells only in non-metastatic tumors. These data suggest that MIG targets cytotoxic T cells. Their recruitment into breast carcinoma can play a critical role in malignant progression, inhibiting the production of metastasis.
文摘Due to continuous scaling of CMOS, stability is a prime concerned for CMOS SRAM memory cells. As scaling will increase the packing density but at the same time it is affecting the stability which leads to write failures and read disturbs of the conventional 6T SRAM cell. To increase the stability of the cell various SRAM cell topologies has been introduced, 8T SRAM is one of them but it has its limitation like read disturbance. In this paper we have analyzed a novel PP based 9T SRAM at 45 nm technology. Cell which has 33% increased SVNM (Static Voltage Noise Margin) from 6T and also 22%.reduced leakage power. N curve analysis has been done to find the various stability factors. As compared to the 10T SRAM cell it is more area efficient.
文摘目的:探究chemerin对银屑病患者外周血辅助性T淋巴细胞9(helper T cells 9,Th9)/调节性T淋巴细胞(regulatory T cells,Treg)免疫平衡的调节作用及其潜在的机制。方法:选取25例银屑病患者和20例健康志愿者,采用磁珠分离法分离出受试者外周血中CD4+T细胞,行实时RT-PCR和ELISA检测细胞中chemerin和其受体chemR23的表达;用不同浓度的chemerin(50,100,150,200 ng/mL)分别处理从健康志愿者外周血分离得到的CD4+T细胞,行MT T比色法检测细胞活力以筛选最适浓度;采用ELISA检测炎性细胞因子水平;行流式细胞术检测Th9和Treg细胞数。结果:与对照相比,银屑病患者外周血中chemerin和chemR23的表达均显著增加,T h 9/Treg比例明显上升(均P<0.05);选取最适浓度150 ng/mL的chemerin处理CD4+T细胞后,细胞中白细胞介素(IL)-6,IL-9和IL-17的水平均显著增加,Th9/Treg比例明显上升(均P<0.05),而chemR23沉默可反转chemerin对CD4+T细胞的上述作用(均P<0.05)。结论:Chemerin通过chemR23调节银屑病患者外周血CD4+T淋巴细胞中的T h 9/Treg细胞免疫平衡。
