DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine

Colorectal cancer (CRC) is a multifaceted disease influenced by the interplay of genetic and environmental factors. The clinical heterogeneity of CRC cannot be attributed exclusively to genetic diversity and environmental exposures, and epigenetic markers, especially DNA methylation, play a critical role as key molecular markers of cancer. This review compiles a comprehensive body of evidence underscoring the significant involvement of DNA methylation modifications in the pathogenesis of CRC. Moreover, this review explores the potential utility of DNA methylation in cancer diagnosis, prognostics, assessment of disease activity, and prediction of drug responses. Recognizing the impact of DNA methylation will enhance the ability to identify distinct CRC subtypes, paving the way for personalized treatment strategies and advancing precision medicine in the management of CRC

Compact Bandwidth-Enhanced 180-Degree Phase Shifter Using Edge-Coupled Multi-Microstrip and Artificial Transmission Line

Compactness has obtained sufficient importance in wideband phase shifter design considerations, as it is directly related to fabrication cost. In this paper, a novel structure was presented to create compact broadband 180-degree phase shifter, which has the advantages of enhanced bandwidth and significantly reduced chip area. The proposed configuration consists of edge-coupled multi-microstrip lines (ECMML) and an artificial transmission line (ATL) with dual-shorted inductors, both of which have the periodic shunt load of capacitors. The ECMML can provide a high coupling coefficient, leading to an increase in the bandwidth, while the introduced capacitors can greatly reduce the line length (35.8% of the conventional method). To verify the relevant mechanisms, a wideband switched network with compact dimensions of 0.67 × 0.46 mm2 was designed via 0.15-micrometer GaAs pHEMT technology. Combined with the measured switch transistor, it was shown that the proposed phase shifter exhibits an insertion loss of less than 2 dB, a return loss of greater than 12 dB, a maximum phase error of less than 0.6° and a channel amplitude difference of less than 0.1 dB in the range of 10 to 20 GHz

A Facile Strategy for Fabrication Lysozyme-Loaded Mesoporous Silica Nanotubes from Electrospun Silk Fibroin Nanofiber Templates

This paper presents a facile and low-cost strategy for fabrication lysozyme-loaded mesoporous silica nanotubes (MSNTs) by using silk fibroin (SF) nanofiber templates. The “top-down method” was adopted to dissolve degummed silk in CaCl2/ formic acid (FA) solvent, and the solution containing SF nanofibrils was used for electrospinning to prepare SF nanofiber templates. As SF contains a large number of -OH, -NH2 and -COOH groups, the silica layer could be easily formed on its surface by the Söber sol-gel method without adding any surfactant or coupling agent. After calcination, the MSNTs were obtained with inner diameters about 200 nm, the wall thickness ranges from 37 ± 2 nm to 66 ± 3 nm and the Brunauer–Emmett–Teller (BET) specific surface area was up to 200.48 m2/g, the pore volume was 1.109 cm3/g. By loading lysozyme, the MSNTs exhibited relatively high drug encapsulation efficiency up to 31.82% and an excellent long-term sustained release in 360 h (15 days). These results suggest that the MSNTs with the hierarchical structure of mesoporous and macroporous will be a promising carrier for applications in biomacromolecular drug delivery systems

Leukamenin E Induces K8/18 Phosphorylation and Blocks the Assembly of Keratin Filament Networks Through ERK Activation

Leukamenin E is a natural ent-kaurane diterpenoid isolated from Isodon racemosa (Hemsl) Hara that has been found to be a novel and potential keratin filament inhibitor, but its underlying mechanisms remain largely unknown. Here, we show that leukamenin E induces keratin filaments (KFs) depolymerization, largely independently of microfilament (MFs) and microtubules (MTs) in well-spread cells and inhibition of KFs assembly in spreading cells. These effects are accompanied by keratin phosphorylation at K8-Ser73/Ser431 and K18-Ser52 via the by extracellular signal-regulated kinases (ERK) pathway in primary liver carcinoma cells (PLC) and human umbilical vein endothelial cells (HUVECs). Moreover, leukamenin E increases soluble pK8-Ser73/Ser431, pK18-Ser52, and pan-keratin in the cytoplasmic supernatant by immunofluorescence imaging and Western blotting assay. Accordingly, leukamenin E inhibits the spreading and migration of cells. We propose that leukamenin E-induced keratin phosphorylation may interfere with the initiation of KFs assembly and block the formation of a new KFs network, leading to the inhibition of cell spreading. Leukamenin E is a potential target drug for inhibition of KFs assembly