CX3CL1 and its receptor CX3CR1 interact with RhoA signaling to induce paclitaxel resistance in gastric cancer.

C-X3-C motif chemokine ligand 1 (CX3CL1) is a transmembrane protein, and the membranal and soluble forms of CX3CL1 exhibit different functions, although both bind to the CX3CR1 chemokine receptor. The CX3CL1/CX3CR1 axis induces many cellular responses relevant to cancer, such as proliferation, migration, invasion, and apoptosis resistance. Here we attempt to elucidate whether CX3CL1/CX3CR1 is associated with paclitaxel (PTX) resistance in gastric cancer (GC). The Gene Expression Omnibus database was queried to screen for differentially expressed genes in GC cells caused by drug resistance, and CX3CL1 was selected as a candidate. CX3CL1 was overexpressed in PTX-resistant cells and tissues. CX3CL1 loss sensitized GC cells to PTX, promoted apoptosis and DNA damage, and inhibited cell proliferation, migration, and invasion. CX3CR1 reversed the ameliorative effect of CX3CL1 silencing on PTX sensitivity in GC cells. The promotion of PTX resistance by CX3CL1/CX3CR1 was inhibited by impairment of the small GTPase Ras homolog gene family member A (RhoA) pathway in vitro and in vivo. These findings indicate that the CX3CL1/CX3CR1 expedites PTX resistance through the RhoA signaling in GC cells.

Constructing a novel type-â ¡ ZnO/BiOCOOH heterojunction microspheres for the degradation of tetracycline and bacterial inactivation.

A novel ZnO/BiOCOOH microsphere photocatalyst with a type-Ⅱ mechanism was developed for the first time. This strategy was accomplished by immobilizing ZnO onto 3D BiOCOOH microspheres via a single-step hydrothermal synthesis method. The ability to degrade tetracycline (TC) in water under visible light and inactivate bacteria of as-catalyst were analyzed. Among the prepared samples, the ZnO/BiOCOOH composite, with a mass ratio of 40%(Zn/Bi), exhibited the highest photocatalytic activity, which was able to degrade 98.22% of TC in just 90 min and completely eradicated Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in 48 h, and had potential application in solving water resource environmental pollution. The photoelectric characteristics of the photocatalysts were examined by means of electrochemical impedance spectroscopy (EIS) and photoluminescence (PL) spectroscopy. The findings indicated that the superior photocatalytic performance could be credited to the dissociation of electrons (e-) and holes (h+) in heterojunction composites. Finally, electron paramagnetic resonance (EPR) and capture experiments were conducted to confirm the photocatalytic mechanism of the type-Ⅱ heterojunction. This work provides a new Bi-base photocatalyst for aqueous environmental control.

Bioactive Phytochemicals and Molecular Mechanisms of Artemisiae capillariae against Drug Induced Liver Injury based on Network Pharmacology.

BACKGROUND: Artemisiae capillariae (Yinchen, YC) is a well-known herbal medicine used to treat drug-induced liver diseases, while the bioactive phytochemicals and pharmacological targets of YC remain unclear. OBJECTIVE: The study aimed to probe the key active components in YC and determine the potential molecular mechanisms of YC protect against DILI. METHODS: In this study, we first delved into the active chemicals and targets of YC, identified potential anti-AILI targets for YC, mapped the components-targets network, performed proteinprotein interaction (PPI) analysis, gene ontology (GO) enrichment, and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analyses of the action targets. This led to figure out the liver protective mechanism of YC against AILI. Analyzing the molecular docking of key targets, binding domain of ingredients and targets reveals the effective interaction, and the binding energy explains the efficiency and stability of the interactions. RESULTS: Network analysis identified 53 components in YC; by systematic screening 13 compounds were selected, which were associated with 123 AILI-related genes. The core ingredients were quercetin, capillarisin and Skrofulein, and the identified crucial genes were AKT1, TNF, and IL6. The GO and KEGG pathway enrichment analysis results indicated that the anti-AILI targets of YC mainly take a part in the regulation of oxidative stress and immune, with related signaling pathways including PI3K/AKT and IL17. Furthermore, the binding pockets of YC bioactive ingredients and key targets were revealed, and the binding ability was proved by molecular docking analysis. CONCLUSION: This study has revealed the potential bioactive molecules and mechanism of YC in AILI and provided a possible strategy for the identification of active phytochemicals against druginduced liver injury.