Targeting TRAF6/IRF3 axis to inhibit NF-κB-p65 nuclear translocation enhances the chemosensitivity of 5-FU and reverses the proliferation of gastric cancer.

Chemoresistance poses a significant clinical challenge in the treatment of gastric cancer (GC), while its underlying molecular mechanisms are still not fully understood. Post-translational protein modification and abnormal activation of nuclear factor-kappa B (NF-κB) are critical regulators of tumor chemoresistance. This study investigates the role of TNF receptors-associated factors 6 (TRAF6) in 5-Fluorouracil (5-FU) resistant GC.

Load bearing characteristics of a new support structure for rapid repair of damaged tunnels and related field tests.

To address the need for rapid repair and emergency support of traffic capacity in damaged tunnels, this study proposed a new structure combining arches assembled from steel plates and shotcrete with high early strength and performance (hereinafter referred to as the steel-shotcreting structure) based on the concept of "modular assembly, rapid formation, and temporary-permanent combination". It is designed to replace the traditional cast-in-place concrete arch repair technique. Based on the principle of equivalent stiffness, the load borne by the steel arches in the new support structure was analyzed.

The forecasting of surface displacement for tunnel slopes utilizing the WD-IPSO-GRU model.

To quickly assess slope stability based on field displacement monitoring data, this paper constructs a hybrid optimization model that predicts surface displacement during tunnel excavation in base-overburden slopes. The model combines Wavelet Decomposition (WD) with a Gated Recurrent Unit (GRU), and the GRU's hyperparameters are optimized using an Improved Particle Swarm Optimization algorithm (IPSO). The specific steps are as follows: First, the Wavelet Decomposition (WD) technique is applied to decompose the raw displacement data, extracting features at different time-frequency scales.

The long noncoding RNA HNF1A-AS1 with dual functions in the regulation of cytochrome P450 3A4.

Cytochrome P450 3A4 (CYP3A4) is the most important and abundant drug-metabolizing enzyme in the human liver. Inter-individual differences in the expression and activity of CYP3A4 affect clinical and precision medicine. Increasing evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in the regulation of CYP3A4 expression.

PRMT1 promotes the proliferation and metastasis of gastric cancer cells by recruiting MLXIP for the transcriptional activation of the β-catenin pathway.

Protein arginine methyltransferase 1 (PRMT1), a type I PRMT, is overexpressed in gastric cancer (GC) cells. To elucidate the function of PRMT1 in GC, PRMT1 expression in HGC-27 and MKN-45 cells was knocked down by short hairpin RNA (shRNA) or inhibited by PRMT1 inhibitors (AMI-1 or DCLX069), which resulted in inhibition of GC cell proliferation, migration, invasion, and tumorigenesis and . MLX-interacting protein (MLXIP) and Kinectin 1 (KTN1) were identified as PRMT1-binding proteins.

Effects of ABCB1 DNA methylation in donors on tacrolimus blood concentrations in recipients following liver transplantation.

Aims: To investigate the effects of ABCB1 DNA methylation in donors on individual differences in tacrolimus blood concentrations following liver transplantation.

Methods: Twenty-three donor liver samples carrying the CYP3A5*3/*3 genotype were classified into 2 groups based on their initial tacrolimus blood concentrations (C  >10 μg/L or <5 μg/L) following liver transplantation. ABCB1 mRNA levels in liver tissues and HepG2 cells were determined by quantitative reverse transcriptase polymerase chain reaction.

Nup54-induced CARM1 nuclear importation promotes gastric cancer cell proliferation and tumorigenesis through transcriptional activation and methylation of Notch2.

Gastric cancer (GC) has the fifth highest incidence globally, but its molecular mechanisms are not well understood. Here, we report that coactivator-associated arginine methyltransferase 1 (CARM1) is specifically highly expressed in gastric cancer and that its overexpression correlates with poor prognosis in patients with gastric cancer. Nucleoporin 54 (Nup54) was identified as a CARM1-interacting protein that promoted CARM1 nuclear importation.

The Long Noncoding RNA Hepatocyte Nuclear Factor 4 Antisense RNA 1 Negatively Regulates Cytochrome P450 Enzymes in Huh7 Cells via Histone Modifications.

The maintenance of homeostasis of cytochromes P450 enzymes (P450s) under both physiologic and xenobiotic exposure conditions is ensured by the action of positive and negative regulators. In the current study, the hepatocyte nuclear factor 4 (HNF4A) antisense RNA 1 (HNF4A-AS1), an antisense long noncoding RNA of , was found to be a negative regulator of the basal and rifampicin (RIF)-induced expression of nuclear receptors and downstream P450s. In Huh7 cells, knockdown of HNF4A-AS1 resulted in elevated expression of HNF4A, pregnane X receptor (PXR), and P450s (including CYP3A4) under both basal and RIF-induced conditions.

Rapalogues as hCES2A Inhibitors: In Vitro and In Silico Investigations.

Background And Objective: Rapamycin and its semi-synthetic analogues (rapalogues) are frequently used in combination with other prescribed medications in clinical settings. Although the inhibitory effects of rapalogues on cytochrome P450 enzymes (CYPs) have been well examined, the inhibition potentials of rapalogues on human esterases have not been investigated. Herein, the inhibition potentials and inhibitory mechanisms of six marketed rapalogues on human esterases are investigated.

DNA methylation determines the regulation of pregnane X receptor on CYP3A4 expression.

The expression and activity of CYP3A4 vary among individuals. With the development of epigenetics, it is now possible to elucidate interindividual differences in drug-metabolizing enzymes. Here, we aimed to explore the potential relationship between DNA methylation and CYP3A4 expression.

A Unidirectional Soft Dielectric Elastomer Actuator Enabled by Built-In Honeycomb Metastructures.

Dielectric elastomer actuators (DEAs) are able to undergo large deformation in response to external electric stimuli and have been widely used to drive soft robotic systems, due to their advantageous attributes comparable to biological muscles. However, due to their isotropic material properties, it has been challenging to generate programmable actuation, e.g.

The HNF1-Regulated LncRNA HNF1-AS1 Is Involved in the Regulation of Cytochrome P450 Expression in Human Liver Tissues and Huh7 Cells.

Expression of cytochrome P450s (P450s) is regulated by epigenetic factors, such as DNA methylation, histone modifications, and noncoding RNAs through different mechanisms. Among these factors, long noncoding RNAs (lncRNAs) have been shown to play important roles in the regulation of gene expression; however, little is known about the effects of lncRNAs on the regulation of P450 expression. The aim of this study was to explore the role of lncRNAs in the regulation of P450 expression by using human liver tissues and hepatoma Huh7 cells.

[Prey selection by tiger frog larvae (Hoplobatrachus chinensis) of two sympatric anuran species' tadpoles].

We examined the prey selection and behavioral responses of tiger frog Hoplobatrachus chinensis larvae exposed to unpalatable and palatable sympatric prey tadpoles, Bufo melanostictus and Pelophylax nigromaculatus. We found that after a short exposure to the toxic toad tadpoles B. melanostictus, predators may learn to decrease going after unpalatable prey, subsequently it seems they may express short-term behavioral memory in order to avoid the toxic prey.