ABSTRACT
Hepatocellular carcinoma (HCC) is the most common type of primary liver malignancy, with increased mortality and morbidity. Accumulating evidence suggested that 40S ribosomal protein S24 (RPS24) is related to malignant outcomes and progression. However, the role of RPS24 remains unclear in HCC. The mRNA and protein expression pattern of RPS24 in HCC was explored and confirmed based on the bioinformatics analysis and histological examination. The correlation between RPS24 expression and clinicopathological features, diagnostic value, prognosis, methylation status, and survival were evaluated. Then, we divided the HCC cohort into two groups based on the expression of RPS24, and performed the functional enrichment and immune cells infiltration analysis of RPS24. Furthermore, in vivo and in vitro experiments were performed to investigate the effect of RPS24 on HCC cells. RPS24 was observed to be elevated in HCC samples. RPS24 overexpression or RPS24 promoter methylation contributed to an unfavorable prognosis for HCC patients. The genes in the high RPS24 expression group were mainly enriched in DNA replication, cell cycle E2F targets, and the G2M checkpoint pathway. Moreover, the expression level of RPS24 was significantly related to immune infiltration and immunotherapy response. Our experiments also demonstrated that RPS24 knockdown suppressed the growth of HCC cells and tumor proliferation of the xenograft model. Therefore, RPS24 can be a potential adverse biomarker of HCC prognosis acting through facilitating cell proliferation and the formation of an immunosuppressive microenvironment in HCC. Targeting RPS24 may offer a promising therapeutic option for HCC management.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Ribosomal Proteins/genetics , Cell Cycle , Cell Division , Tumor Microenvironment/geneticsABSTRACT
Interferon (IFN) regulates immune responses and antitumor activity. Arginine-glycine-aspartic acid (RGD) peptides can specifically bind to integrin αvß3, a transmembrane receptor that is highly expressed on the surface of various cancer cells. In this study, we expressed recombinant RGD-IFN-α2a-core fusion proteins and assessed their antitumor activity in vitro. Two RGD-IFN-α2a-core fusion proteins and a negative control protein were expressed in vitro. These two RGD-IFN-α2a-core fusion proteins could bind the tumor cell surface specifically and did not bind to normal cells. RGD-IFN-α2a-core fusion protein treatment of tumor cells significantly reduced cell viability and induced apoptosis in a dose-dependent manner. At the 'mRNA' level, both proteins could upregulate CASP3 expression. These data indicate that both laboratory-engineered RGD-IFN-α2a-core fusion proteins could bind the surface of tumor cells and induce apoptosis in vitro. Further studies will investigate the in-vivo antitumor activities of the RGD-IFN-α2a-core fusion proteins.
Subject(s)
Antineoplastic Agents/pharmacology , Interferon-alpha/pharmacology , Oligopeptides/pharmacology , Recombinant Fusion Proteins/pharmacology , A549 Cells , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Cell Line, Tumor , Cloning, Molecular , Colonic Neoplasms/drug therapy , Drug Screening Assays, Antitumor , Humans , Interferon-alpha/biosynthesis , Interferon-alpha/genetics , Lung Neoplasms/drug therapy , Oligopeptides/biosynthesis , Oligopeptides/genetics , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/geneticsABSTRACT
Elucidating the structural composition of a three-dimensional amorphous sodium-aluminosilicate-hydrate (Na2O-Al2O3-SiO2-H2O, N-A-S-H) gel in geopolymers is a prerequisite for its prevailing application in biomaterials, construction, waste management, and climate change mitigation. An unsolved challenge in geopolymer science is the clear structural understanding of amorphous N-A-S-H doped with desired metals. Here, we uncover the molecular structure of (Zn)-N-A-S-H, confirming the tetrahedral coordination of Zn with O and the presence of Si-O-Zn bonds. The Zn-Si distance of â¼3.0-3.1 Å proves the connection of the corners of ZnO42- tetrahedra and SiO4 tetrahedra by slight twisting. The stoichiometric formula of the ZnO-doped geopolymer is quantified as (Na0.19Zn0.02AlSi1.74O5.095)·0.19H2O. The remarkable antimicrobial efficacy of the Zn modified-geopolymer in inhibiting the formation of biofilms by the sulphur-oxidising bacteria Acidithiobacillus thiooxidans and inhibiting biogenic acidification is evidenced. The biodegradation process of the geopolymer featuring the rupture of the Si-O-Al and Si-O-Zn bonds of the networks leads to the expelling of tetrahedral AlO4- and ZnO42- from the aluminosilicate framework and the eventual formation of the siliceous structure. This work demonstrates that the (Zn)-N-A-S-H structure of our new geopolymer provides a solution to optimising geopolymer materials and provides further possibilities for designing novel geopolymer composites for use in construction materials, antibacterial biomaterials in dental or bone surgery, and management of hazardous and radioactive waste.
Subject(s)
Zinc Oxide , Zinc , Zinc/chemistry , Silicon Dioxide , Anti-Bacterial AgentsABSTRACT
The structural characteristics of raw coal and hydrogen peroxide (H(2)O(2))-oxidized coals were investigated using scanning electron microscopy, X-ray diffraction (XRD), Raman spectra, and Fourier transform infrared (FT-IR) spectroscopy. The results indicate that the derivative coals oxidized by H(2)O(2) are improved noticeably in aromaticity and show an increase first and then a decrease up to the highest aromaticity at 24 h. The stacking layer number of crystalline carbon decreases and the aspect ratio (width versus stacking height) increases with an increase in oxidation time. The content of crystalline carbon shows the same change tendency as the aromaticity measured by XRD. The hydroxyl bands of oxidized coals become much stronger due to an increase in soluble fatty acids and alcohols as a result of the oxidation of the aromatic and aliphatic C-H bonds. In addition, the derivative coals display a decrease first and then an increase in the intensity of aliphatic C-H bond and present a diametrically opposite tendency in the aromatic C-H bonds with an increase in oxidation time. There is good agreement with the changes of aromaticity and crystalline carbon content as measured by XRD and Raman spectra. The particle size of oxidized coals (<200 nm in width) shows a significant decrease compared with that of raw coal (1 µm). This study reveals that the optimal oxidation time is â¼24 h for improving the aromaticity and crystalline carbon content of H(2)O(2)-oxidized coals. This process can help us obtain superfine crystalline carbon materials similar to graphite in structure.
ABSTRACT
The structural characteristics of the raw coal (AY), the H2O2 oxidized coals (AY-H2O2) and the HF acidized AY-H2O2 (AY-H2O2-HF) were investigated by SEM, X-ray diffraction, Raman and FTIR spectroscopy. The results indicate that the derivative coals show an obvious increase in the aromaticity, crystalline carbon content and hydroxyl content, especially the AY-H2O2-HF. The stacking layer number of crystalline carbon decreases and the aspect ratio (La/Lc) remarkably increases for AY-H2O2 and AY-H2O2-HF. The crystalline layers become much thinner. The particle size of AY-H2O2-HF in width significantly decreases from 1 µm to less than 100 nm. The combination of H2O2 oxidization and HF acidification is effective to reduce the size of the aromatic layers and to increase the reactivity of derivative coals. The process can help us obtain the superfine crystalline carbon materials like graphite structure.