ABSTRACT
Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assay, glucose uptake assay, Oil Red O staining, cell viability assay, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mammalian target of rapamycin (mTOR) signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, and glucose uptake, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.NEW & NOTEWORTHY Transcription factor forkhead box M1 (FOXM1) regulates glycolysis, fatty acid biosynthesis, and cellular energy consumption, which, together, controls cell growth and patient prognosis in colorectal cancer (CRC).
Subject(s)
Colorectal Neoplasms , Forkhead Box Protein M1 , Humans , Forkhead Box Protein M1/metabolism , Forkhead Box Protein M1/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , HT29 Cells , HCT116 Cells , Glycolysis , Gene Expression Regulation, Neoplastic , Warburg Effect, Oncologic , Signal Transduction , Cell Proliferation , Cellular Reprogramming/physiology , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins c-akt/metabolism , Metabolic ReprogrammingABSTRACT
Three groups of zirconia abutments (n = 5) consisting of different connection designs or manufacturers were investigated (All-Zr, ASC-Zr, and AM-Zr groups). All-electric dynamic test instruments were used to place static loading on a specimen with a crosshead speed set at 1 mm/min. A Kruskal-Wallis test and a post hoc Mann-Whitney U test were used for statistical evaluation. The mean fracture resistance was 252.37 ± 82.79 N for the All-Zr group, 384.62 ± 45.24 N for ASC-Zr group, and 361.83 ± 90.31 N for the AM-Zr group. The difference of fracture resistance between the three groups was marginally significant (Kruskal-Wallis test, p = 0.054), with the ASC zirconia abutment tending to have higher fracture resistance than the full zirconia abutment. The modes of failure among the three types of abutments are different. The All-Zr group showed an oblique fracture line starting from the buccal aspect at the region of the implant platform. While the ASC-Zr and AM-Zr groups showed a relatively horizontal fracture line with a greater distance from the implant platform. The titanium inserts cannot significantly improve the fracture resistance of the zirconia abutment. However, they may alter the modes of failure, allowing buccal fracture surfaces of the zirconia abutments to be placed away from the implant platform, thereby protecting the implant-abutment connection.
ABSTRACT
The use of aftermarket computer-aided design/computer-assisted manufacturing (CAD/CAM) prosthesis components in dental implants has become popular. This study aimed to (1) compare the accuracy of aftermarket CAD/CAM screws with that of original equipment manufacturer (OEM) abutment screws and (2) examine the biomechanical effects of different abutment screws used with zirconia abutment in an implant fixture by using three-dimensional finite element analysis (FEA). Significantly different measurements were obtained for the aftermarket CAD/CAM and OEM screws. The FEA results indicated that under the same loading condition, the maximum stress of the aftermarket CAD/CAM screws was 15.9% higher than that of the OEM screws. Moreover, the maximum stress position occurred in a wide section of the OEM screws but in the narrowest section of the aftermarket screws. The stress of the OEM zirconia abutment was 14.9% higher when using the aftermarket screws than when using the OEM screws. The effect of the manufacturing differences between aftermarket and OEM screws on the clinical effect of aftermarket screws is unpredictable. Therefore, aftermarket screws should be cautiously used clinically.