(NK) cells are at the first line of defence against tumours, but their anti-tumour mechanisms are not fully understood. We aimed to investigate the mechanism by which NK cells can mediate immunotherapy against head and neck squamous cell carcinoma (HNSCC). We collected fifty-two pairs of HNSCC tissues and corresponding adjacent normal tissues; analysis by RT-qPCR showed underexpression of CXCL14 in HNSCC tissues. Primary NK cells were then isolated from the peripheral blood of HNSCC patients and healthy donors. CXCL14 was found to be consistently under-expressed in the primary NK cells from the HNSCC patients. However, CXCL14 expression was increased in IL2-activated primary NK cells and NK-92 cells. We next evaluated NK cell migration, IFN-γ and TNF-α expression, cytotoxicity and infiltration in response to CXCL14 overexpression or knockdown using gain- and loss-of-function approach. The results exhibited that CXCL14 overexpression promoted NK cell migration, cytotoxicity and infiltration. Subsequent in vivo experiments revealed that CXCL14 suppressed the growth of HNSCC cells via activation of NK cells. ChIP was applied to study the enrichment of H3K27ac, p300, H3K4me1 and CDX2 in the enhancer region of CXCL14, which showed that CDX2/p300 activated the enhancer of CXCL14 to up-regulate its expression. Rescue experiments demonstrated that CDX2 stimulated NK cell migration, cytotoxicity and infiltration through up-regulating CXCL14. In vivo data further revealed that CDX2 suppressed tumorigenicity of HNSCC cells through enhancement of CXCL14. To conclude, CDX2 promotes CXCL14 expression by activating its enhancer, which promotes NK cell–mediated immunotherapy against HNSCC. 相似文献
Thrombocytopenia is independently related with increased mortality in severe septic patients. Renin-angiotensin system (RAS) is elevated in septic subjects; accumulating studies show that angiotensin II (Ang II) stimulate the intrinsic apoptosis pathway by promoting reactive oxygen species (ROS) production. However, the mechanisms underlying the relationship of platelet apoptosis and RAS system in sepsis have not been fully elucidated. The present study aimed to elucidate whether the RAS was involved in the pathogenesis of sepsis-associated thrombocytopenia and explore the underlying mechanisms. We found that elevated plasma Ang II was associated with decreased platelet count in both patients with sepsis and experimental animals exposed to lipopolysaccharide (LPS). Besides, Ang II treatment induced platelet apoptosis in a concentration-dependent manner in primary isolated platelets, which was blocked by angiotensin II type 1 receptor (AT1R) antagonist losartan, but not by angiotensin II type 2 receptor (AT2R) antagonist PD123319. Moreover, inhibiting AT1R by losartan attenuated LPS-induced platelet apoptosis and alleviated sepsis-associated thrombocytopenia. Furthermore, Ang II treatment induced oxidative stress level in a concentration-dependent manner in primary isolated platelets, which was partially reversed by the AT1R antagonist losartan. The present study demonstrated that elevated Ang II directly stimulated platelet apoptosis through promoting oxidative stress in an AT1R-dependent manner in sepsis-associated thrombocytopenia. The results would helpful for understanding the role of RAS system in sepsis-associated thrombocytopenia. 相似文献
Molecular Breeding - The stem color of young mung bean is a very useful tool in germplasm identification. Flowering time and plant height (PH) are known to be strongly correlated with crop adaption... 相似文献
In the paper, resonances of different waveguide structures with various vertical indirect coupled cavities were investigated by FDTD (finite difference-time domain). In the silicon cavity, Fano resonance could be observed at about 1430 nm. The coupling distance for the gold cavity/air cavity had less effect on the transmittance of the main waveguide but had a great influence on the transmission for water cavity in the visible region, which showed that water cavity could adjust resonance of waveguide structures. In addition, with the increment of refractive index n, the resonance peak at about 850 nm moved to the long wavelength (redshift). Dispersion rate about 2 × 10–3/nm indicated that the transparent dielectric selectively absorbed the surface plasmon polariton wave and the sensitivity of the waveguide structure designed in this paper has high stability for the refractive index of the main waveguide cavity. Obvious Fano resonance could be observed with the increase of refractive index for silicon cavity. Among the four dielectrics, silicon and water are suitable for studying Fano resonance and filter dielectrics.
There is increasing evidence suggesting that dysregulation of certain microRNAs (miRNAs) may contribute to tumor progression and metastasis. Previous studies have shown that miR-409-3p is dysregulated in some malignancies, but its role in bladder cancer is still unknown. Here, we find that miR-409-3p is down-regulated in human bladder cancer tissues and cell lines. Enforced expression of miR-409-3p in bladder cancer cells significantly reduced their migration and invasion without affecting cell viability. Bioinformatics analysis identified the pro-metastatic gene c-Met as a potential miR-409-3p target. Further studies indicated that miR-409-3p suppressed the expression of c-Met by binding to its 3′-untranslated region. Silencing of c-Met by small interfering RNAs phenocopied the effects of miR-409-3p overexpression, whereas restoration of c-Met in bladder cancer cells bladder cancer cells overexpressing miR-409-3p, partially reversed the suppressive effects of miR-409-3p. We further showed that MMP2 and MMP9 may be downstream effector proteins of miR-409-3p. These findings indicate that miR-409-3p could be a potential tumor suppressor in bladder cancer. 相似文献