Search

A growing amount of evidence has indicated immune genes perform a crucial position in the development and progression of breast cancer microenvironment. The purpose of our study was to identify immunogenic prognostic marker and explore potential regulatory mechanisms for breast cancer. We identified the genes related to ImmuneScore using ESTIMATE algorithm and WGCNA analysis, and we identified the differentially expressed gene (DEGs). Then, Glia maturation factor γ (GMFG) was determined as a predictive factor by intersecting immune-related genes with DEGs and survival analysis. We found the expression of GMFG was lower in breast cancer tissues compared with normal breast tissues, which was further verified by immunohistochemical (IHC). Moreover, the decreased expression of GMFG was significantly related to the poor prognosis. Besides, the expression of GMFG was related to the age, ER status, PR status, HER2 status and tumor size, which further suggested that the expression of GMFG was correlated with the subtype and the growth of tumor. The univariate and multivariate Cox regression analyses revealed that age, stage, the expression level of GMFG and radiotherapy were independent factors for predicting the prognosis of breast cancer patients. Subsequently, a prognostic model to predict the 3-year, 5-year and 10-year overall survival rate was developed based on the above four variables, and visualized as a nomogram. The values of area under the curve of the nomogram at 3-year, 5-year and 10-year were 0.897, 0.873 and 0.922, respectively, which was higher than stage in prognostic accuracy. In addition, we also found that GMFG expression level was correlated with sensitivity of some breast cancer chemotherapy drugs. Furthermore, the results of GSEA indicated immune-related pathways were mainly enriched in GMFG-high-expression group. CIBERSORT analysis for the proportion of tumor-infiltrating immune cells (TIICs) suggested that expression of GMFG was positively association with multiple kinds T-cell in BC. Among them, CD8+ T cells had the strongest correlation with GMFG expression, which revealed that GMFG might has an antitumor effect by increasing the infiltration of CD8+ T cells in breast cancer. Accordingly, GMFG has the potential to become a novel immune biomarker for the diagnosis and treatment of breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, He, Tang, Shao, Song, Gong, Zeng, Huang, Zhou, Wan, Wei and Zhang.)

Gastric cancer (GC) is one of the most common malignant neoplasms of the digestive system, with China leading in terms of morbidity and mortality rates. Betulinic acid (BA) is a widely-occurring pentacyclic triterpenoid that has been reported to exhibit potent anti-inflammatory, antioxidant, and antitumor activities. BA can combat tumors by inducing apoptosis, regulating cell cycle, and inhibiting autophagy, but its mechanism of action in the context of GC is unclear. A preliminary study found that higher expression of vasodilator-stimulated phosphoprotein (VASP) was correlated with migration in the GC cell line. In this study, BGC-823 cells and MNK45 cells were treated with BA for investigating its effect on the proliferation and migration of cells. Moreover, the expression of VASP and upstream signal molecules were also investigated in this background. The results showed BA could inhibit the proliferation and migration the GC cells. Furthermore, NF-κB acted as a transcription factor to upregulate VASP expression. Moreover, BA could downregulate the expression of VASP at the protein and mRNA level by inhibiting NF-κB activity. In conclusion, these results suggest that BA could inhibit the expression of VASP by negatively regulating NF-κB, thereby inhibiting the proliferation and migration of the GC cells. Our study provides a theoretical basis for exploring the molecular mechanism underlying BA-induced inhibition of proliferation and migration in GC cells., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Recently, an increasing number of studies have revealed that N6-methyladenosine (m6A) functions as a significant post-transcriptional modification which plays a critical role in the occurrence and progression of enriched tumors by regulating coding and non-coding RNA biogenesis. However, the biological function of m6A in breast cancer remains largely unclear., Materials and Methods: In this study, we used a series of bioinformatic databases and tools to jointly analyze the expression of m6A methylation transferases (METTL3, METTL14, WTAP, RBM15, RBM15B and ZC3H13) and investigate the prognostic value of METTL14 and ZC3H13 in breast cancer. Besides, we analyzed the downstream carcinogenic molecular mechanisms related to METTL14 and ZC3H13 and their relationship with immune infiltration in breast tumor tissues., Results: The results showed that METTL14 and ZC3H13 were the down-regulated m6A methylation transferases in breast cancer. Survival outcome analysis suggested that abnormally low expression of METTL14 and ZC3H13 could predict unfavorable prognosis in four breast cancer subtypes. Moreover, their down-regulation was associated with ER-, PR- and triple-negative breast cancer patients, as well as tumor progression (increased Scarff, Bloom and Richardson grade status and Nottingham Prognostic Index classification). Co-expression analysis revealed that METTL14 and ZC3H13 had a strong positive correlation with APC, an antagonist of the Wnt signaling pathway, indicating they might cooperate in regulating proliferation, invasion, and metastasis of tumor cells. METTL14, ZC3H13, and APC expression levels had significant positive correlation with infiltrating levels of CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, and negative correlation with Treg cells in breast cancer., Conclusions: This study demonstrated that down-regulation of METTL14 and ZC3H13 which act as two tumor suppressor genes was found in breast cancer and predicted poor prognosis. Their abnormal expression promoted breast cancer invasion by affecting pathways related to tumor progression and mediating immunosuppression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Gong, Shao, Yang, Song, He, Zeng, Huang, Wei and Zhang.)

Objective: Many primary tumors have insufficient supply of molecular oxygen, called hypoxia. Hypoxia is one of the leading characteristics of solid tumors resulting in a higher risk of local failure and distant metastasis. It is quite necessary to investigate the hypoxia associated molecular hallmarks in breast cancer., Materials and Methods: According to the published studies, we selected 13 hypoxia related gene expression signature to define the hypoxia status of breast cancer using ConsensusClusterPlus package based on the data from The Cancer Genome Atlas (TCGA). Subsequently, we characterized the infiltration of 24 immune cell types under different hypoxic conditions. Furthermore, the differentially expressed hypoxia associated microRNAs, mRNAs and related signaling pathways were analyzed and depicted. On this basis, a series of prognostic markers related to hypoxia were identified and ceRNA co-expression networks were constructed., Results: Two subgroups (cluster1 and cluster2) were identified and the 13 hypoxia related gene signature were all up-regulated in cluster1. Thus, we defined the cluster1 as "hypoxic subgroup" compared with cluster2. The infiltration of CD8+ T cell and CD4+ T cell were lower in cluster1 while the nTreg cell and iTreg cell were higher, indicating that there was immunosuppressive status in cluster1. We observed widespread hypoxia-associated dysregulation of microRNAs and mRNAs. Next, a risk signature for predicting prognosis of breast cancer patients was established based on 12 dysregulated hypoxia associated prognostic genes. Two microRNAs, hsa-miR-210-3p and hsa-miR-190b, with the most significant absolute logFC value were related to unfavorable and better prognosis, respectively. Several long non-coding RNAs were predicted to be microRNA targets and positively correlated with two selected mRNAs, CPEB2 and BCL11A. Predictions based on the SNHG16-hsa-miR-210-3p-CPEB2 and LINC00899/PSMG3-AS1/PAXIP-AS1-hsa-miR-190b-BCL11A ceRNA regulation networks indicated that the two genes might act as tumor suppressor and oncogene, respectively., Conclusion: Hypoxia plays an important role in the initiation and progression of breast cancer. Our research provides potential mechanisms into molecular-level understanding of tumor hypoxia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Gong, Shao, Huang, Zeng, Yuan, Xu, Yin, Wei and Zhang.)

By virtue of combining an in-situ assembly process with a stepwise synthesis in conventional aqueous solution, two series of unique organic-inorganic hybrid heteropolyoxomolybdates were constructed from plenary Keggin germanomolybdates and Cu-Ln heterometallic units and fully characterized: [H 2 INA] 2 H 8 [LnCu(INA) 4 (H 2 O) 6 ] 2 [α-GeMo 12 O 40 ] 3 ⋅52 H 2 O (Ln=La 3+ (1), Ce 3+ (2), Pr 3+ (3), Nd 3+ (4), Sm 3+ (5), Eu 3+ (6); HINA=isonicotinic acid) and (NH 4 )[Cu(PA) 2 ][Cu(PA) 2 Ln(H 2 O) 8 ][α-GeMo 12 O 40 ]⋅10 H 2 O (Ln=Nd 3+ (7), Sm 3+ (8), Eu 3+ (9); HPA=picolinic acid). The most remarkable structural characteristic of compounds 1-6 was that their molecular units were defined by three discrete plenary Keggin [α-GeMo 12 O 40 ] 4- polyoxoanions and two organic-inorganic hybrid heterometallic [LnCu(INA) 4 (H 2 O) 6 ] + moieties, whereas compounds 7-9 exhibited a nice-looking 1D chain-like structure that was built from plenary [α-GeMo 12 O 40 ] 4- polyoxoanions, pendent [Cu(PA) 2 ] complexes, and bridging {[Cu(PA) 2 ][Ln(H 2 O) 8 ]} 3+ heterometallic groups. Notably, two different pyridine carboxylic acid ligands led to the discrepancy between the two structure types. To the best of our knowledge, compounds 1-9 constitute the first examples of plenary Keggin heterometallic germanomolybdates that include Cu-Ln-organic subunits. Further studies revealed that compounds 3 and 8 exhibited fast adsorption capacity for cationic dyes methylene blue (MB) and rhodamine B (RhB) in water. Moreover, compounds 3 and 8 could quickly and selectively adsorb MB from a mixture of MB/methyl orange (MO) or MB/azophloxine (Apo)., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Polyethyleneimine nanogels (named as M-PEIs) with different sizes were prepared by photo-Fenton reaction in aqueous solution from which samples of 38, 75, 87, 121, 132 and 167nm were selected for in vitro transfection. The homogeneous structure and the same component made it possible to study the size effect of M-PEIs nanogels on gene transfection efficiency when loading the same quantity of plasmid DNA (pLEGFP-C1) into A549, Bel7402, BGC-823 and Hela cells. M-PEIs and its DNA complexes were characterized by photo correlation spectroscopy and atomic force microscopy. The protein expression was observed by flow cytometry and fluorescence microscopy. All of the DNA complexes had no obvious cytotoxicity and the surface charges were positive charged at the optimum weight ratio. Therefore, the expressed protein was affected by the size of M-PEIs when the same quantity of DNA was used to transfect cells. In addition, the samples of 75 and 87nm yielded the highest transfection efficiency about 30% in all of the four cell lines which were also cell line independent.

53 subjects with normal binocular single vision and normal stereoacuity (SA) were performed the Titmus Stereo Test while degrading the visual acuity (VA) monocularly and binocularly with graded hazy films. The results showed that SA impairment with monocular decrement was more than with binocular symmetrical decrement at each VA level. The authors inferred that imbalance of VA between the two eyes in infants and children was harmful to the development of binocular vision, and that partial occlusion therapy would be more favorable for the binocular visual development of amblyopic children. Also, it was suggested to include SA in the criteria for cure of amblyopia.

Analogues of yeast alanyl tRNA with I34 replaced by A34 or G34 were synthesized. Synthetic analogues of yeast alanyl tRNT occupy the same position as the natural yeast alanyl tRNA on polyacrylamide gel electrophoresis, and their purity is about 95% after electrophoresis on a 10% or 20% polyacrylamide gel. The two terminal and nearest neighbour nucleotides of the analogues are all correct. The accepting activity of the synthetic analogues is similar to that of the reconstituted natural yeast alanyl tRNA. The incorporation activity of alanine into proteins of the synthetic analogues is about 30% of that of the natural of reconstituted natural yeast alanyl tRNA when I34 is replaced by A, and is 90% when I34 is replaced by G. The reason of the variation in biological function of the analogues of yeast alanyl tRNA after I34 replaced by A or G was discussed.

Three analogs of yeast alanyl tRNA with anticodon loops of different sizes, tRNA75 (no G35 and 5'-terminal phosphate), tRNA77 (one more C between G35 and C36, no 5'-terminal phosphate), and ptRNA79 (with Cm1I psi between G35 and C36), were synthesized. In comparison with the reconstituted natural yeast tRNA, the charging activities of the three analogs were 90% (tRNA75), 94.7% (tRNA77), and 104% (ptRNA79). These results supported the conclusion (Yang De-ping and Wang De-bao (T. P. Wang) (1983) Acta Biochim. Biophys. Sin. 15, 83-90) that the anticodon loop of yeast alanyl tRNA was not involved in the interaction between alanyl-tRNA synthetase from rat liver and yeast alanyl tRNA. In contrast, in the rabbit reticulocyte lysate system, the incorporation of alanine in the charged analogs was 0% (tRNA75 and ptRNA79) and 100% (tRNA77). There were significant differences between the incorporation activities of analogs and those of the reconstituted molecule. The reason for these differences is discussed.