28 results on '"Hao, Yating"'
Search Results
2. Application of deep learning in analysing morphological parameters of cervical computed tomography scans
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Li, Yuan, Zhang, Enlong, Ouyang, Hanqiang, Liu, Xiaoming, Pang, Huacheng, Hao, Yating, Hu, Daole, Dong, Shuyu, Shi, Xiangjun, Tian, Shuai, Dong, Pei, Jiang, Liang, Lang, Ning, and Yuan, Huishu
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- 2024
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3. Exact solutions to the (3+1)-dimensional time-fractional KdV–Zakharov–Kuznetsov equation and modified KdV equation with variable coefficients
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Hao, Yating and Gao, Ben
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- 2024
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4. Long non-coding RNA HANR modulates the glucose metabolism of triple negative breast cancer via stabilizing hexokinase 2
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Han, Guohui, Bai, Xiangdong, Li, Feng, Huang, Li, Hao, Yating, Li, Weina, Bu, Peng, Zhang, Huanhu, Liu, Xinxin, and Xie, Jun
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- 2024
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5. Particle flow regime in a swirling pneumatic conveying system
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Ji, Yun, Hao, Yating, Yi, Ning, Guan, Tianyuan, and Gao, Dianrong
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- 2022
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6. Crystal structure of 6,6′-((1E,1′E)-((2-phenylpyrimidine-4,6-diyl)bis(hydrazin-2-yl-1-ylidene))bis(methaneylylidene))bis(2-methoxyphenol)monohydrate, C26H26N6O5.
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Hao, Yating, Pan, Pan, Lan, Hairong, Lu, Jiaxing, Wan, Yan, and Chu, Yixin
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CRYSTAL structure - Abstract
C26H26N6O5, monoclinic, P21/c (no. 14), a = 10.9393(1) Å, b = 16.8724(2) Å, c = 13.5836(2) Å, β = 102.843(1)°, V = 2444.43(5) Å3, Z = 4, Rgt(F) = 0.0318, wRref(F2) = 0.0827, T = 173 K. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Crystal structure of 6,6′-((1E,1′E)-((2-phenylpyrimidine-4,6-diyl)bis(hydrazin-2-yl-1-ylidene))bis(methaneylylidene))bis(2-methoxyphenol)monohydrate, C26H26N6O5.
- Author
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Hao, Yating, Pan, Pan, Lan, Hairong, Lu, Jiaxing, Wan, Yan, and Chu, Yixin
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CRYSTAL structure - Abstract
C
26 H26 N6 O5 , monoclinic, P21 /c (no. 14), a = 10.9393(1) Å, b = 16.8724(2) Å, c = 13.5836(2) Å, β = 102.843(1)°, V = 2444.43(5) Å3 , Z = 4, Rgt (F) = 0.0318, wRref (F2 ) = 0.0827, T = 173 K. [ABSTRACT FROM AUTHOR]- Published
- 2024
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8. Cancer cell‐derived exosomal miR‐20a‐5p inhibits CD8+ T‐cell function and confers anti‐programmed cell death 1 therapy resistance in triple‐negative breast cancer.
- Author
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Li, Weina, Han, Guohui, Li, Feng, Bu, Peng, Hao, Yating, Huang, Li, and Bai, Xiangdong
- Abstract
Circulating miRNAs (cirmiRNAs) can be packaged into the exosomes, participating in intercellular communication, which affects the malignant progression and therapy resistance of triple‐negative breast cancer (TNBC). Currently, immune checkpoint inhibitors that regulate T‐cell function, especially antibodies against programmed cell death 1 (PD‐1) or its ligand PD‐L1, are emerging as new promising therapy for TNBC patients. However, only very limited patients showed complete or partial response to anti‐PD‐1 treatment. Dysfunction of CD8+ T cells is one of the key reasons for the immune escape of TNBC. The regulation of exosome‐derived cirmiRNAs on CD8+ T cells in TNBC deserves more investigation. Here, the cirmiR‐20a‐5p level was significantly upregulated in the plasma of TNBC patients and culture supernatant of TNBC cells. High abundance of cirmiR‐20a‐5p was correlated with a worse prognosis of TNBC. cirmiR‐20a‐5p was secreted in the form of exosomes by TNBC cells. Exosomal cirmiR‐20a‐5p was internalized into CD8+ T cells and resulted into the dysfunction of CD8+ T. A mechanism study uncovered that cirmiR‐20a‐5p targeted the nuclear protein ataxia‐telangiectasia (NPAT) and decreased NPAT expression in CD8+ T cells. An in vivo xenograft mouse model showed that cirmiR‐20a‐5p conferred TNBC to anti‐PD‐1 treatment resistance. Collectively, these findings indicated that cirmiR‐20a‐5p released by TNBC cells via exosome promotes cancer cell growth and leads to the immunosuppression by inducing CD8+ T cell dysfunction. This study suggests that targeting cirmiR‐20a‐5p might be a novel strategy for overcoming the resistance of TNBC to anti‐PD‐1 immunotherapy. [ABSTRACT FROM AUTHOR]
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- 2024
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9. The Effect of a Three-Blade Tube on the Pneumatic Transport of Pebble Particles.
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Hao, Yating, Chen, Hongyu, and Ji, Yun
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SWIRLING flow , *CENTRIFUGAL force , *PEBBLES , *FLOW velocity , *PARTICLE spin , *FLUIDIZATION , *ROTATIONAL motion , *PARTICLE motion - Abstract
In this paper, the Computational Fluid Dynamics–Discrete Element Method (CFD-DEM) coupling method was used to simulate the pneumatic transport of pebble particles in a three-blade spiral tube. The results showed that the flow field distribution rotated along the circumference after loading. The maximum velocity of the flow field after loading was manifested as rotation along the circumference. In addition, the swirl intensity decreased exponentially with the increase in conveying distance, and the maximum swirl intensity had a saturation value. After reaching the saturation value, it is not evident that increasing the initial air velocity significantly affected swirl variation. The smaller the pitch, the greater the initial swirl intensity. The swirling flow was conducive to the fluidization of particles, but it would bring a significant energy loss. Increasing the swirl can increase the degree of particle dispersion. There is an optimal tangential airflow velocity, which allows the particles to fully spin and stay in the suspension zone without being thrown onto the pipe wall by excessive centrifugal force. At this time, the energy efficiency reaches the highest level. A 5.87 m/s velocity was deemed the optimal tangential airflow velocity for conveying 3 mm particles. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Reduced PTEN involved in primary immune thrombocytopenia via contributing to B cell hyper-responsiveness
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Wang, Shixuan, Guan, Yue, Wang, Yunlong, Li, Huiyuan, Zhang, Donglei, Ju, Mankai, Hao, Yating, Song, Xuewen, Sun, Boyang, Dou, Xueqing, and Yang, Renchi
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- 2018
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11. Increased plasma sCXCL16 levels may have a relationship with Th1/Th2 imbalance in primary immune thrombocytopenia
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Hao, Yating, Li, Yang, Li, Huiyuan, Lyu, Mingen, Zhang, Donglei, Fu, Rongfeng, Guan, Yue, Wang, Shixuan, Sun, Boyang, Dou, Xueqing, Zhang, Lei, and Yang, Renchi
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- 2017
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12. Synthesis, Biological Evaluation, DNA Binding, and Molecular Docking of Hybrid 4,6-Dihydrazone Pyrimidine Derivatives as Antitumor Agents.
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Lan, Hairong, Song, Junying, Yuan, Juan, Xing, Aiping, Zeng, Dai, Hao, Yating, Zhang, Zhenqiang, and Feng, Shuying
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HYDRAZONE derivatives ,MOLECULAR docking ,PYRIMIDINE derivatives ,ANTINEOPLASTIC agents ,DNA ,MOLECULAR hybridization - Abstract
In the present paper, on the basis of molecular hybridization, a series of 4,6-dihydrazone pyrimidine derivatives containing the pyridine moiety were synthesized, structurally characterized, and evaluated in vitro for their antitumor activity. According to the results, all the tested compounds demonstrated broad-spectrum antitumor activity against selected tumor cell lines (MCF-7, BGC-823, A549, and BEL-7402) and no obvious toxicity toward normal cells HL-7702. In particular, compounds 10a and 10f were found to be the most promising antitumor agents among the tested compounds against BGC-823 cells (IC
50 = 9.00 μM and 7.89 μM) and BEL-7402 cells (IC50 = 6.70 μM and 7.66 μM), respectively. Compounds 10a and 10f exhibited higher potency against BGC-823 and BEL-7402 than the positive control 5-FU (IC50 = 15.18 μM and 15.81 μM). Further mechanism investigations demonstrated that compounds 10a and 10f could significantly increase the level of cellular ROS and induce early apoptosis of BGC-823 cells in a dose-dependent manner. Moreover, the DNA binding results from UV/Vis, CD spectroscopy, and molecular docking studies indicated that 10a and 10f bind with DNA via groove binding and partial intercalation. These results demonstrated that 10a and 10f may serve as novel lead compounds for the discovery of more dihydrazone pyrimidine derivatives with improved antitumor potency and selectivity. [ABSTRACT FROM AUTHOR]- Published
- 2023
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13. Comparison of Axial Flow and Swirling Flow on Particle Pickup in Horizontal Pneumatic Conveying.
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Ji, Yun, Hao, Yating, Yi, Ning, Guan, Tianyuan, Gao, Dianrong, and Liang, Yingna
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AXIAL flow , *GRANULAR flow , *PNEUMATIC-tube transportation , *SWIRLING flow , *PRESSURE drop (Fluid dynamics) , *TWO-phase flow - Abstract
Pneumatic conveying is widely used in coal mining. As the lowest conveying velocity of materials, the pickup velocity is the key to the study of gas–solid two-phase flow. In this study, the pickup velocity of pebble particles was experimentally investigated. When the particle size is 3–9 mm, the airflow velocity was found to suitably describe the results as a function of the pickup velocity and have a high correlation. When the swirl number is 0.2, the optimal swirl number was found for which the highest particle pickup ratio was observed. Based on four different methods, namely, visual observation, mass weighing, coefficient of difference analysis, and determination of the peak-average ratio of the pressure drop in the flow field to measure the pickup velocity of the spraying material, the results showed that the accuracy of the particle pickup velocity obtained through visual observation was the lowest, and when the mass–loss rate of the particle was selected as the measurement index of the pickup velocity, the accuracy was the highest. The results will help to realize the long-distance transportation of spraying materials in inclined roadway under the shaft. [ABSTRACT FROM AUTHOR]
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- 2022
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14. Decreased TLR4 expression on monocytes may cause regulatory T cells abnormality in patients with primary immune thrombocytopenia.
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Hao, Yating, Li, Huiyuan, Li, Yang, Lyu, Mingen, Zhang, Donglei, Fu, Rongfeng, Guan, Yue, Wang, Shixuan, Sun, Boyang, Dou, Xueqing, and Yang, Renchi
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AUTOIMMUNE diseases , *TOLL-like receptors , *T cells , *THROMBOCYTOPENIA , *CYTOKINES - Abstract
Primary immune thrombocytopenia (ITP) is an autoimmune disease with many immune dysfunctions including T helper type 1 cell (Th1) polarization and regulatory T cells (Tregs) deficiency. This study aimed to determine the effects of TLR4 on Treg differentiation and the cytokine production of peripheral blood mononuclear cells (PBMCs) from patients with ITP. We found that expression of TLR4 on monocytes was significantly decreased in patients with active ITP than that in healthy controls and it had positive correlation with platelet count. However, there was no expression of TLR4 on CD4+ T cells. The result of further experimentsin vitroshowed that lipopolysaccharide (LPS) stimulation could enhance TLR4 expression on monocytes. Additionally, activation of TLR4 with LPS could promote differentiation of Treg cells and anti-TLR4 attenuated this effect. There was no significant difference about Th17 cells among three subgroups. However, the Th17/Treg cell ratio was decreased after stimulation with LPS and increased with anti-TLR4. Moreover, activation of TLR4 with LPS could significantly promote the secretion of interleukin-10 (IL-10) and transforming growth factor-β1 (TGFB1), while anti-TLR4 significantly suppressed the secretion of them. Nevertheless, the secretion of IL-17A did not reach the statistical difference among three subgroups. In summary, decreased TLR4 appears to cause Tregs abnormality in ITP by modulating Tregs differentiation and immunoregulatory cytokines. [ABSTRACT FROM AUTHOR]
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- 2017
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15. Numerical and functional defects in CD8+CD28− T-suppressor lymphocytes from patients with primary immune thrombocytopenia.
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Li, Huiyuan, Hao, Yating, Zhang, Donglei, Liu, Wenjie, Li, Yang, Lyu, Mingen, Fu, Rongfeng, Xue, Feng, Liu, Xiaofan, and Yang, Renchi
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IDIOPATHIC thrombocytopenic purpura , *AUTOIMMUNE diseases , *IMMUNOLOGICAL tolerance , *SUPPRESSOR cells , *FLOW cytometry , *T cells - Abstract
Primary immune thrombocytopenia ( ITP) is an acquired autoimmune disorder, and loss of immune tolerance has been implicated in ITP pathogenesis. CD8+CD28− suppressor (Ts) cells have an immunosuppression function and are involved in several autoimmune disorders. However, the role of Ts cells in ITP is currently not clear. Here, flow cytometry was used to detect the CD8+CD28−CD127− proportion, which was decreased in active ITP patients compared with that of controls. Function analysis showed that immunosuppression of CD8+CD28− Ts cells in ITP patients was impaired. Mechanistic studies have shown that CD8+CD28− Ts cells from controls can downregulate CD80 and upregulate LILRB4 (ITL3) and LILRB2 (ILT4) expression on CD14+ monocytes, whereas these abilities were not found in Ts cells from ITP patients. Furthermore, Inducible T-cell costimulatory ( ICOS) expression on the Ts cell surface after activation was decreased whereas programmed death 1 and interleukin 10 expression was not changed in ITP patients compared with those of controls. In summary, the down-regulated quantity and function of Ts cells in active patients indicated that a Ts defect was involved in ITP. Moreover, decreased ICOS expression and the loss of the ability to regulate co-stimulator expression on antigen-presenting cells partly explained the defective Ts-mediated suppression. [ABSTRACT FROM AUTHOR]
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- 2017
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16. Upregulation of CD72 expression on CD19+CD27+ memory B cells by CD40L in primary immune thrombocytopenia.
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Lyu, Mingen, Hao, Yating, Li, Yang, Lyu, Cuicui, Liu, Wenjie, Li, Huiyuan, Xue, Feng, Liu, Xiaofan, and Yang, Renchi
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CD antigens , *B cells , *IDIOPATHIC thrombocytopenic purpura , *DISEASE remission , *INTERLEUKINS , *INTERLEUKIN-10 - Abstract
CD72 is a co-receptor of B cells and regulates B cell activation. Although aberrant expression of CD72 has been reported in primary immune thrombocytopenia ( ITP), it is uncertain whether this aberrant expression is restricted to specific B cell subsets. Furthermore, the mechanisms that regulate CD72 expression are unknown. In this study, we found higher frequency of CD19+ B cells, CD19+CD27+ memory B cells and lower frequency of CD19+CD27− naive B cells in active ITP patients compared with controls and patients in remission. CD72 expression on CD19+CD27+ cells was upregulated in active ITP patients and correlated with platelet count and anti-platelet autoantibodies. In vitro, CD40L could specifically induce CD72 upregulation on CD19+CD27+ B cells. In combination with CD40L, interleukin ( IL) 10 and BAFF (also termed TNFSF13B) further enhanced CD72 expression on CD19+CD27+ B cells, whereas IL21 reduced CD72 upregulation. CD72 mRNA expression after CD40L stimulation was increased in ITP patients and controls. Significant increase of CD40L on CD4+ T cells was correlated with CD72 expression on CD19+CD27+ B cells in ITP patients. In conclusion, upregulation of CD72 expression on CD27+memory B cells might take part in the pathogenesis of ITP. Elevated CD40L on CD4+ cells combined with cytokines might contribute to the upregulation of CD72 expression on CD27+memory B cells. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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17. Aberrant expression of long noncoding RNA TMEVPG1 in patients with primary immune thrombocytopenia.
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Li, Huiyuan, Hao, Yating, Zhang, Donglei, Fu, Rongfeng, Liu, Wenjie, Zhang, Xian, Xue, Feng, and Yang, Renchi
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THROMBOCYTOPENIA , *MESSENGER RNA , *INTERFERON gamma , *T helper cells , *AUTOIMMUNITY - Abstract
TMEVPG1 is a long noncoding RNA, which can promote Interferon gamma (IFNG) transcript as an enhancer. It has been reported that plasma IFNG concentration was elevated and partly due to dysregulation of micro RNAs in patients with primary immune thrombocytopenia (ITP). However, the effect of long noncoding RNA on IFNG expression in ITP is currently not well understood. To explore whether TMEVPG1 is involved in ITP, this study examined the TMEVPG1 expression and analyzed the association between TMEVPG1 transcript and IFNG expression in patients with ITP and healthy controls. The result showed that TMEVPG1 expression in peripheral blood mononuclear cells (PBMCs) from active ITP patients were lower than in that of healthy controls. Further activation for 24 hin vitroresulted in decreased TMEVPG1 while elevated IFNG mRNA and protein expressions in activated PBMCs compared with un-activated PBMCs both in ITP patients and healthy controls. However, TMEVPG1 and IFNG mRNA had same up-regulated tendency after short-time activation (1, 2 and 4 h) in healthy controls. In addition, we detected T helper 1 (Th1) cell associated transcription factors T-bet, STAT1 and STAT4 mRNA levels, and found T-bet mRNA expression was lower in PBMCs from ITP patient in remission compared with healthy controls. In conclusion, we speculated that TMEVPG1 could promote IFNG transcription, and IFNG over-expression negative feedback regulated on TMEVPG1 expression, which resulted in decreased TMEVPG1 in ITP patients. [ABSTRACT FROM PUBLISHER]
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- 2016
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18. Effects of the multidrug resistance-1 gene on drug resistance in primary immune thrombocytopenia.
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Liu, Wenjie, Li, Huiyuan, Zhang, Donglei, Lv, Mingen, Li, Yang, Hao, Yating, Chen, Yunfei, Liu, Xiaofan, Xue, Feng, Zhang, Lei, and Yang, Renchi
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THROMBOCYTOPENIA ,GENE expression ,MULTIDRUG resistance ,LYMPHOCYTES ,MESSENGER RNA ,GENETICS - Abstract
Primary immune thrombocytopenia (ITP) is an autoimmune disorder that is characterized by low platelet count. Glucocorticoids (GCs) resistance is a great challenge in the treatment of ITP. P-glycoprotein (P-gp) is a widely studied protein, which is associated with drug resistance. However, in ITP, the functional activity and immune regulation mechanism of P-gp remain uncertain. In this study, we evaluated the expression and functional activity of P-gp in different lymphocyte subsets, explored the correlation between P-gp function and GCs resistance and investigated the role of P-gp in ITP pathogenesis. Results indicated that the functional activity and mRNA level of P-gp were significantly higher in GCs-nonresponsive patients than in GCs-responsive patients with ITP. However, these differences in P-gp were only significant in CD8
+ T cells. P-gp function was related to disease activity rather than GCs therapy. P-gp was involved in secreting granzyme B and perforin, maintaining autoreactive lymphocytes survival and enhancing autologous platelets lysis in ITP. In conclusion, over-functional P-gp might play an important role in the pathogenesis of ITP and induce GCs resistance in nonresponsive ITP patients. The blockage of P-gp could be a promising therapeutic approach for GCs-resistant patients with ITP. [ABSTRACT FROM AUTHOR]- Published
- 2016
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19. Stromal cell-derived factor-1 rs2297630 polymorphism associated with platelet production and treatment response in Chinese patients with chronic immune thrombocytopenia.
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Lyu, Mingen, Li, Yang, Hao, Yating, Sun, Tiantian, Liu, Wenjie, Lyu, Cuicui, Fu, Rongfeng, Li, Huiyuan, Xue, Feng, Liu, Xiaofan, Zhang, Lei, and Yang, Renchi
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STROMAL cells ,GENETIC polymorphisms ,BLOOD platelet examination ,IDIOPATHIC thrombocytopenic purpura ,MEDICAL research ,PATIENTS ,THERAPEUTICS - Abstract
Stromal cell-derived factor-1 (SDF-1), signaling through CXCR4, is implicated in megakaryopoiesis and platelet production. SDF-1 rs2297630 is a functional polymorphism in linkage disequilibrium with other functional variants in SDF-1. This study aimed to investigate the role of SDF-1 rs2297630 in chronic ITP. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing. Immature platelet fraction (IPF) was performed using Sysmex XE-2100. Anti-platelet autoantibodies were assayed by enzyme-linked immunosorbent assay. The main characteristics at diagnosis and the outcome of chronic ITP in 201 Chinese patients were retrospectively reviewed. There was no significant difference in either genotype or allelic distribution between ITP patients and the controls (p= 0.114;p= 0.787). However, both heterozygote (GA) and homozygote minor allele (AA) patients had significantly increased megakaryocyte quantity compared to homozygote genotype (GG) patients at diagnosis (p =0.011). The mean IPF values of GA and AA genotype patients were higher than those observed in the GG genotype patients when platelet counts ≤50 × 109/L at diagnosis (p= 0.007). Patients with GA and AA genotype showed a higher response rate to standard treatments than patients with GG genotype (p< 0.001). In particular, GA and AA genotype patients had a significantly increased chance of responding to steroids, intravenous immunoglobulin (IVIG), and thrombopoietin analogs (p= 0.007;p= 0.029;p= 0.034, respectively). No significant difference was found between anti-platelet antibodies and genotypes (p= 0.296). In summary, the SDF-1 rs2297630 was associated with platelet production and treatment response in Chinese patients with chronic ITP. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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20. The risk assessment method oriented to mechanical safety design.
- Author
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Wang, Qing, Hao, Yating, and Wang, Chaoqun
- Abstract
The most fundamental means of maintaining mechanical safety is to systematically carry out safety design and analysis in the mechanical design process. The fuzzy comprehensive evaluation method is to take the advantages of the level analytic hierarchy process and fuzzy comprehensive evaluation method. Firstly, the evaluation index system is divided into ladder level structure, calculated the index weight using AHP. Secondly, the single factor is evaluated using fuzzy evaluation matrix. Lastly, the mechanical risk is comprehensively evaluated through this method. [ABSTRACT FROM PUBLISHER]
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- 2012
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21. Decreased immunosuppressive actions of 1α, 25-dihydroxyvitamin D3 in patients with immune thrombocytopenia.
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Liu, Wenjie, Li, Huiyuan, Hao, Yating, Li, Yang, Lv, Mingen, Xue, Feng, Liu, Xiaofan, Zhang, Lei, and Yang, Renchi
- Subjects
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T cells , *IMMUNOSUPPRESSION , *THROMBOCYTOPENIA , *AUTOIMMUNE diseases , *IMMUNE system - Abstract
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease. 1α, 25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] and vitamin D receptor (VDR) play important immune-suppressive roles in immune system. It has been reported that serum 1,25(OH) 2 D 3 were lower in ITP patients. In this study, we evaluated local 1,25(OH) 2 D 3 level and VDR mRNA expression further, and determined whether 1,25(OH) 2 D 3 /VDR were correlated with T cell dysfunction in ITP patients. We found that 1,25(OH) 2 D 3 /VDR levels were decreased in active ITP patients, and 1,25(OH) 2 D 3 had significant anti-inflammatory effects on ITP patients, including both anti-proliferation of peripheral blood mononuclear cells (PBMCs) and reversing the abnormal T cells polarization. 1,25(OH) 2 D 3 inhibited the differentiation of T helper (Th)1 and Tc1 cells but induced the differentiation of Th2, Tc2 and T regulatory (Treg) cells in ITP patients. However, the percentage of Th17 cells were not affected obviously with 1,25(OH) 2 D 3 . In addition, 1,25(OH) 2 D 3 also suppressed pro-inflammatory cytokines (INF-γ and IL-17A) but promoted anti-inflammatory cytokine (IL-10) secretion in ITP patients. In conclusion, decreased 1,25(OH) 2 D 3 /VDR might participate in the pathogenesis of ITP, and appropriate supplement of 1,25(OH) 2 D 3 may be a promising treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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22. Elevated Semaphorin 5A correlated with Th1 polarization in patients with chronic immune thrombocytopenia.
- Author
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Lyu, Mingen, Li, Yang, Hao, Yating, Sun, Tiantian, Liu, Wenjie, Lyu, Cuicui, Fu, Rongfeng, Li, Huiyuan, Xue, Feng, Liu, Xiaofan, Zhang, Lei, and Yang, Renchi
- Subjects
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SEMAPHORINS , *CELLULAR immunity , *IDIOPATHIC thrombocytopenic purpura , *IMMUNODEFICIENCY , *STATISTICAL correlation , *CYTOKINES , *PATIENTS , *THERAPEUTICS - Abstract
Background Primary immune thrombocytopenia (ITP) is an immune-mediated disorder in which cellular immunity deficiency and disturbed cytokine profiles have been found. Semaphorin 5A (Sema5A) has been showed to be implicated in cellular immune response. We aimed to evaluate the role of Sema5A in patients with chronic ITP. Methods Plasma levels of Sema5A, T helper (Th) cytokines (interferon [IFN] -γ,interleukin [IL]-4,IL-17A) were determined by enzyme-linked immunosorbent assay (ELISA) in ITP patients and healthy controls. Using real-time quantitative polymerase chain reaction (RT-PCR), mRNA levels of Sema5A and its receptor plexin-B3, plexin-A1 in peripheral blood mononuclear cells(PBMCs)were studied in all subjects. Specific anti-platelet autoantibodies were measured by the Pak Auto method. The dynamic change of plasma Sema5A and mRNA levels of its receptors was measured in 9 patients after effective therapy. Results Plasma Sema5A levels were significantly increased in active patients with chronic ITP compared to patients in remission and healthy controls. Elevated levels of Sema5A were found positively correlated with higher levels of plasma IFN-γ, IFN-γ/IL-4 ratio and negatively correlated with lower levels of plasma IL-4, platelet counts in ITP patients. The mRNA plexin-B3 was decreased in active ITP patients and inversely correlated with plasma Sema5A levels. Additionally, plasma levels of Sema5A and IFN-γ were reduced with up-regulation of plexin-B3 expression after effective treatment. Conclusions Our data demonstrated elevated plasma Sema5A in chronic ITP patients might be involved in Th1 polarization by down-regulating receptor plexin-B3 expression and correlated with disease activity. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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23. Cancer cell-derived exosomal miR-20a-5p inhibits CD8 + T-cell function and confers anti-programmed cell death 1 therapy resistance in triple-negative breast cancer.
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Li W, Han G, Li F, Bu P, Hao Y, Huang L, and Bai X
- Subjects
- Humans, Animals, Mice, CD8-Positive T-Lymphocytes metabolism, Cell Line, Tumor, Cell Proliferation physiology, B7-H1 Antigen genetics, MicroRNAs genetics, MicroRNAs metabolism, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms metabolism
- Abstract
Circulating miRNAs (cirmiRNAs) can be packaged into the exosomes, participating in intercellular communication, which affects the malignant progression and therapy resistance of triple-negative breast cancer (TNBC). Currently, immune checkpoint inhibitors that regulate T-cell function, especially antibodies against programmed cell death 1 (PD-1) or its ligand PD-L1, are emerging as new promising therapy for TNBC patients. However, only very limited patients showed complete or partial response to anti-PD-1 treatment. Dysfunction of CD8
+ T cells is one of the key reasons for the immune escape of TNBC. The regulation of exosome-derived cirmiRNAs on CD8+ T cells in TNBC deserves more investigation. Here, the cirmiR-20a-5p level was significantly upregulated in the plasma of TNBC patients and culture supernatant of TNBC cells. High abundance of cirmiR-20a-5p was correlated with a worse prognosis of TNBC. cirmiR-20a-5p was secreted in the form of exosomes by TNBC cells. Exosomal cirmiR-20a-5p was internalized into CD8+ T cells and resulted into the dysfunction of CD8+ T. A mechanism study uncovered that cirmiR-20a-5p targeted the nuclear protein ataxia-telangiectasia (NPAT) and decreased NPAT expression in CD8+ T cells. An in vivo xenograft mouse model showed that cirmiR-20a-5p conferred TNBC to anti-PD-1 treatment resistance. Collectively, these findings indicated that cirmiR-20a-5p released by TNBC cells via exosome promotes cancer cell growth and leads to the immunosuppression by inducing CD8+ T cell dysfunction. This study suggests that targeting cirmiR-20a-5p might be a novel strategy for overcoming the resistance of TNBC to anti-PD-1 immunotherapy., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)- Published
- 2024
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24. Long non-coding RNA HANR modulates the glucose metabolism of triple negative breast cancer via stabilizing hexokinase 2.
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Han G, Bai X, Li F, Huang L, Hao Y, Li W, Bu P, Zhang H, Liu X, and Xie J
- Abstract
Increasing evidence has demonstrated the oncogenic roles of long non-coding RNA (lncRNA) hepatocellular carcinoma (HCC)-associated long non-coding RNA (HANR) in the development of HCC and lung cancer; however, the involvement of HANR in triple-negative breast cancer (TNBC) remains largely unknown. Our results demonstrated the significant overexpression of HANR in TNBC tissues and cells. Higher HANR levels significantly correlated with the poorer phenotypes in patients with TNBC. HANR down-regulation inhibited the proliferation and cell cycle progression and increased the apoptosis of TNBC cells. Mechanistically, immunoprecipitation-mass spectrometry revealed hexokinase II (HK2) as a direct binding target of HANR. HANR binds to and stabilizes HK2 through the proteasomal pathway. Consistent with the important role of HK2 in cancer cells, HANR depletion represses the glucose absorbance and lactate secretion, thus reprogramming the metabolism of TNBC cells. An in vivo xenograft model also demonstrated that HANR promoted tumor growth and aerobic glycolysis. This study reveals the role of HANR in modulating the glycolysis in TNBC cells by regulating HK2 stability, suggesting that HANR is a potential drug target for TNBC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
- Published
- 2023
- Full Text
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25. Synthesis, Biological Evaluation, DNA Binding, and Molecular Docking of Hybrid 4,6-Dihydrazone Pyrimidine Derivatives as Antitumor Agents.
- Author
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Lan H, Song J, Yuan J, Xing A, Zeng D, Hao Y, Zhang Z, and Feng S
- Subjects
- Structure-Activity Relationship, Molecular Docking Simulation, Cell Line, Tumor, Pyrimidines chemistry, DNA pharmacology, Drug Screening Assays, Antitumor, Molecular Structure, Cell Proliferation, Drug Design, Antineoplastic Agents chemistry
- Abstract
In the present paper, on the basis of molecular hybridization, a series of 4,6-dihydrazone pyrimidine derivatives containing the pyridine moiety were synthesized, structurally characterized, and evaluated in vitro for their antitumor activity. According to the results, all the tested compounds demonstrated broad-spectrum antitumor activity against selected tumor cell lines (MCF-7, BGC-823, A549, and BEL-7402) and no obvious toxicity toward normal cells HL-7702. In particular, compounds 10a and 10f were found to be the most promising antitumor agents among the tested compounds against BGC-823 cells (IC
50 = 9.00 μM and 7.89 μM) and BEL-7402 cells (IC50 = 6.70 μM and 7.66 μM), respectively. Compounds 10a and 10f exhibited higher potency against BGC-823 and BEL-7402 than the positive control 5-FU (IC50 = 15.18 μM and 15.81 μM). Further mechanism investigations demonstrated that compounds 10a and 10f could significantly increase the level of cellular ROS and induce early apoptosis of BGC-823 cells in a dose-dependent manner. Moreover, the DNA binding results from UV/Vis, CD spectroscopy, and molecular docking studies indicated that 10a and 10f bind with DNA via groove binding and partial intercalation. These results demonstrated that 10a and 10f may serve as novel lead compounds for the discovery of more dihydrazone pyrimidine derivatives with improved antitumor potency and selectivity.- Published
- 2022
- Full Text
- View/download PDF
26. MiR-133 Targets YES1 and Inhibits the Growth of Triple-Negative Breast Cancer Cells.
- Author
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Zhang G, Wang J, Zheng R, Song B, Huang L, Liu Y, Hao Y, and Bai X
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Apoptosis, Biomarkers, Tumor genetics, Cell Movement, Cell Proliferation, Female, Humans, Middle Aged, Phosphorylation, Prognosis, Proto-Oncogene Mas, Proto-Oncogene Proteins c-yes genetics, Transcription Factors genetics, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms surgery, Tumor Cells, Cultured, YAP-Signaling Proteins, Adaptor Proteins, Signal Transducing metabolism, Biomarkers, Tumor metabolism, Gene Expression Regulation, Neoplastic, MicroRNAs genetics, Proto-Oncogene Proteins c-yes metabolism, Transcription Factors metabolism, Triple Negative Breast Neoplasms pathology
- Abstract
Triple-negative breast cancer shows worse outcome compared with other subtypes of breast cancer. The discovery of dysregulated microRNAs and their roles in the progression of triple-negative breast cancer provide novel strategies for the treatment of patients with triple-negative breast cancer. In this study, we identified the significant reduction of miR-133 in triple-negative breast cancer tissues and cell lines. Ectopic overexpression of miR-133 suppressed the proliferation, colony formation, and upregulated the apoptosis of triple-negative breast cancer cells. Mechanism study revealed that the YES Proto-Oncogene 1 was a target of miR-133. miR-133 bound the 3'-untranslated region of YES Proto-Oncogene 1 and decreased the level of YES Proto-Oncogene 1 in triple-negative breast cancer cells. Consistent with miR-133 downregulation, YES1 was significantly increased in triple-negative breast cancer, which was inversely correlated with the level of miR-133. Restoration of YES Proto-Oncogene 1 attenuated the inhibitory effects of miR-133 on the proliferation and colony formation of triple-negative breast cancer cells. Consistent with the decreased expression of YES Proto-Oncogene 1, overexpression of miR-133 suppressed the phosphorylation of YAP1 in triple-negative breast cancer cells. Our results provided novel evidence for the role of miR-133/YES1 axis in the development of triple-negative breast cancer, which indicated miR-133 might be a potential therapeutic strategy for triple-negative breast cancer.
- Published
- 2020
- Full Text
- View/download PDF
27. Numerical and functional defects in CD8 + CD28 - T-suppressor lymphocytes from patients with primary immune thrombocytopenia.
- Author
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Li H, Hao Y, Zhang D, Liu W, Li Y, Lyu M, Fu R, Xue F, Liu X, and Yang R
- Subjects
- Adolescent, Adult, Aged, Cytokines metabolism, Female, Humans, Immune Tolerance physiology, Inducible T-Cell Co-Stimulator Protein metabolism, Interferon-gamma biosynthesis, Interleukin-10 physiology, Lymphocyte Subsets physiology, Male, Middle Aged, Programmed Cell Death 1 Receptor metabolism, Transforming Growth Factor beta1 metabolism, Young Adult, CD28 Antigens metabolism, CD8-Positive T-Lymphocytes physiology, Purpura, Thrombocytopenic, Idiopathic immunology, T-Lymphocytes, Regulatory physiology
- Abstract
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder, and loss of immune tolerance has been implicated in ITP pathogenesis. CD8
+ CD28- suppressor (Ts) cells have an immunosuppression function and are involved in several autoimmune disorders. However, the role of Ts cells in ITP is currently not clear. Here, flow cytometry was used to detect the CD8+ CD28- CD127- proportion, which was decreased in active ITP patients compared with that of controls. Function analysis showed that immunosuppression of CD8+ CD28- Ts cells in ITP patients was impaired. Mechanistic studies have shown that CD8+ CD28- Ts cells from controls can downregulate CD80 and upregulate LILRB4 (ITL3) and LILRB2 (ILT4) expression on CD14+ monocytes, whereas these abilities were not found in Ts cells from ITP patients. Furthermore, Inducible T-cell costimulatory (ICOS) expression on the Ts cell surface after activation was decreased whereas programmed death 1 and interleukin 10 expression was not changed in ITP patients compared with those of controls. In summary, the down-regulated quantity and function of Ts cells in active patients indicated that a Ts defect was involved in ITP. Moreover, decreased ICOS expression and the loss of the ability to regulate co-stimulator expression on antigen-presenting cells partly explained the defective Ts-mediated suppression., (© 2017 John Wiley & Sons Ltd.)- Published
- 2017
- Full Text
- View/download PDF
28. Upregulation of CD72 expression on CD19 + CD27 + memory B cells by CD40L in primary immune thrombocytopenia.
- Author
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Lyu M, Hao Y, Li Y, Lyu C, Liu W, Li H, Xue F, Liu X, and Yang R
- Subjects
- Adult, B-Cell Activating Factor pharmacology, B-Lymphocyte Subsets immunology, CD40 Ligand pharmacology, Case-Control Studies, Cells, Cultured, Female, Humans, Immunologic Memory physiology, Interleukin-10 pharmacology, Interleukins pharmacology, Male, Middle Aged, Up-Regulation immunology, Young Adult, Antigens, CD metabolism, Antigens, CD19 metabolism, Antigens, Differentiation, B-Lymphocyte metabolism, B-Lymphocytes immunology, CD40 Ligand metabolism, Purpura, Thrombocytopenic, Idiopathic immunology, Tumor Necrosis Factor Receptor Superfamily, Member 7 metabolism
- Abstract
CD72 is a co-receptor of B cells and regulates B cell activation. Although aberrant expression of CD72 has been reported in primary immune thrombocytopenia (ITP), it is uncertain whether this aberrant expression is restricted to specific B cell subsets. Furthermore, the mechanisms that regulate CD72 expression are unknown. In this study, we found higher frequency of CD19
+ B cells, CD19+ CD27+ memory B cells and lower frequency of CD19+ CD27- naive B cells in active ITP patients compared with controls and patients in remission. CD72 expression on CD19+ CD27+ cells was upregulated in active ITP patients and correlated with platelet count and anti-platelet autoantibodies. In vitro, CD40L could specifically induce CD72 upregulation on CD19+ CD27+ B cells. In combination with CD40L, interleukin (IL) 10 and BAFF (also termed TNFSF13B) further enhanced CD72 expression on CD19+ CD27+ B cells, whereas IL21 reduced CD72 upregulation. CD72mRNA expression after CD40L stimulation was increased in ITP patients and controls. Significant increase of CD40L on CD4+ T cells was correlated with CD72 expression on CD19+ CD27+ B cells in ITP patients. In conclusion, upregulation of CD72 expression on CD27+ memory B cells might take part in the pathogenesis of ITP. Elevated CD40L on CD4+ cells combined with cytokines might contribute to the upregulation of CD72 expression on CD27+ memory B cells., (© 2017 John Wiley & Sons Ltd.)- Published
- 2017
- Full Text
- View/download PDF
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