Search

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, R gt(F) = 0.0318, wRref (F 2) = 0.0827, T = 173 K.

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]

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]

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]

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]

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 (IC50 = 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]

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.)

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.)