Design, Synthesis, and Biological Evaluation of the Quorum-Sensing Inhibitors of PAO1.

Due to the resistance of Gram-negative bacteria PAO1 to most clinically relevant antimicrobials, the use of traditional antibiotic treatments in hospitals is challenging. The formation of biofilms, which is regulated by the quorum-sensing (QS) system of (PA), is an important cause of drug resistance. There are three main QS systems in : the system, the system, and the system.

Discovery of Novel STING Inhibitors Based on the Structure of the Mouse STING Agonist DMXAA.

The stimulator-of-interferon-gene (STING) protein is involved in innate immunity. The drug DMXAA (5,6-dimethylxanthenone-4-acetic acid) proved to be a potent murine-STING (mSTING) agonist but had little effect on human-STING (hSTING). In this paper, we draw upon the comparison of different crystal structures and protein-ligand interaction relationships analysis to venture the hypothesis that the drug design of DMXAA variants has the potential to convert STING agonists to inhibitors.

Design, synthesis and biological evaluation of acridone analogues as novel STING receptor agonists.

STING (Stimulator of Interferon Genes) has become a focal point in immunology research and a target in drug discovery. The discovery of a potent human-STING agonist is expected to revolutionize current anti-virus or cancer immunotherapy. Inspired by the structure and function of murine STING-specific agonists (DMXAA and CMA), we rationally designed and synthesized four series of novel compounds for the enhancement of human sensitivity.

Design, Synthesis and Biological Evaluation of 1-Phenyl-2-(phenylamino) Ethanone Derivatives as Novel MCR-1 Inhibitors.

Polymyxins are considered to be the last-line antibiotics that are used to treat infections caused by multidrug-resistant (MDR) gram-negative bacteria; however, the plasmid-mediated transferable colistin resistance gene () has rendered polymyxins ineffective. Therefore, the protein encoded by , MCR-1, could be a target for structure-based design of inhibitors to tackle polymyxins resistance. Here, we identified racemic compound as a potential MCR-1 inhibitor by virtual screening, and 26 compound derivatives were synthesized and evaluated in vitro.

Aggregation of Gold Nanoparticles Caused in Two Different Ways Involved in 4-Mercaptophenylboronic Acidand Hydrogen Peroxide.

The difference in gold nanoparticle (AuNPs) aggregation caused by different mixing orders of AuNPs, 4-mercaptophenylboronic acid (4-MPBA), and hydrogen peroxide (HO) has been scarcely reported. We have found that the color change of a ((4-MPBA + AuNPs) + HO) mixture caused by HO is more sensitive than that of a ((4-MPBA + HO) + AuNPs) mixture. For the former mixture, the color changes obviously with HO concentrations in the range of 0~0.

Structural Basis for the Inhibition of the Autophosphorylation Activity of HK853 by Luteolin.

The two-component system (TCS) is a significant signal transduction system for bacteria to adapt to complicated and variable environments, and thus has recently been regarded as a novel target for developing antibacterial agents. The natural product luteolin (Lut) can inhibit the autophosphorylation activity of the typical histidine kinase (HK) HK853 from , but the inhibition mechanism is not known. Herein, we report on the binding mechanism of a typical flavone with HK853 by using solution NMR spectroscopy, isothermal titration calorimetry (ITC), and molecular docking.

Expression patterns of members of the ethylene signaling-related gene families in response to dehydration stresses in cassava.

Drought is the one of the most important environment stresses that restricts crop yield worldwide. Cassava (Manihot esculenta Crantz) is an important food and energy crop that has many desirable traits such as drought, heat and low nutrients tolerance. However, the mechanisms underlying drought tolerance in cassava are unclear.

Salidroside-regulated lipid metabolism with down-regulation of miR-370 in type 2 diabetic mice.

Salidroside is known for its pharmacological properties and in particular its antioxidation effects. In recent years, it has been recognized that salidroside plays an important role in treating diabetes. Accumulated evidence suggests that microRNAs may be involved in diabetic lipid disorders.

Development of PLGA nanoparticles simultaneously loaded with vincristine and verapamil for treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor chemo-sensitivity to vincristine sulfate (VCR) due to multi-drug resistance (MDR). Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo-sensitizer) might be a potential strategy to improve HCC therapeutic efficacy of VCR. PLGA nanoparticles (PLGANPs) simultaneously loaded with VCR and VRP (CVn) were prepared.

Reversion of multidrug resistance by co-encapsulation of vincristine and verapamil in PLGA nanoparticles.

Multidrug resistant (MDR) cancer may be treated using combinations of encapsulated cytotoxic drugs and chemosensitizers. To optimize the effectiveness of this combinational approach, poly(d,l-lactide-co-glycolide acid) (PLGA) nanoparticles formulations capable of delivering a cytotoxic drug, vincristine, a chemosensitizer, verapamil, or their combination were prepared via combining O/W emulsion solvent evaporation and salting-out method. Moreover, this work evaluated a number of approaches for the administration of chemosensitizer-cytotoxic drug combinations in a systematic fashion.