Pseudomonas aeruginosa is one of the most important foodborne pathogens that can persist in leafy green vegetables and subsequently produce biofilms. In this study, the synergistic effect of thymoquinone and nisin in reducing biofilm formation of P. aeruginosa on lettuce was evaluated, and their anti-virulence and anti-biofilm mechanisms were also investigated. At concentrations ranging from 0.5 to 2 mg/ml, thymoquinone inhibited the production of autoinducers and virulence factors, and enhanced the susceptibility of P. aeruginosa biofilms to nisin as evidenced by the scanning electron microscopy and confocal laser scanning microscopy. Integrated transcriptomics, metabolomics, and docking analyses indicated that thymoquinone treatment disrupted the quorum sensing (QS) system, altered cell membrane component, and down-regulated the expressions of genes related to virulence, efflux pump, and antioxidation. The changed membrane component and repressed efflux pump system enhanced membrane permeability and facilitated the entrance of nisin into cells, thus improving the susceptibility of biofilms to nisin. The dysfunctional QS and repressed antioxidant enzymes lead to the enhancement of oxidative stress. The enhanced oxidative stress disrupted energy metabolism and protein metabolism and ultimately attenuated the virulence and pathogenicity of P. aeruginosa PAO1. Our study indicated that thymoquinone has the potential to function as a QS-based agent to defend against foodborne pathogens in combination with nisin.
Hydrogen sulfide releasing agents (or H2S
donors) have
been recognized gasotransmitters with potent cytoprotective and anticancer
properties. However, the clinical application of H2S donors
has been hampered by their fast H2S-release, instability,
and lack of tumor targeting, despite the unclear molecular mechanism
of H2S action. Here we rationally designed an amphiphilic
pentapeptide (RGDFF) to coassemble with the de novo designed thiol-activated H2S donors (CL2/3) into nanocarriers
for targeted therapy of non-small-cell lung cancer, which has been
proved as a one-stone-three-birds strategy. The coassembly approach
simply solved the solubility issue of CL2/3 by the introduction of
electron-donating groups (phenyl rings) to slow down the H2S release while dramatically improving their biocompatible interface,
circulation time, slow release of H2S, and tumor targeting.
Experimental results confirmed that as-prepared coassembled nanocarriers
can significantly induce the intrinsic apoptotic, effectively arrest
cell cycle at the G2/M phase, inhibit H2S-producing enzymes,
and lead to mitochondrial dysfunction by increasing intracellular
ROS production in H1299 cells. The mouse tumorigenesis experiments
further confirmed the in vivo anticancer effects
of the coassembled nanocarriers, and such treatment made tumors more
sensitive to radiotherapy then improved the prognosis of tumor-bearing
mice, which holds great promise for developing a new combined approach
for NSCLC.
There
are two important topics in the field of cancer research:
one is targeted molecular therapy and the other is tumor molecular
imaging. Focal adhesion kinase (FAK) is considered as an attractive
target for oncologic diagnosis and therapy. A series of 2,4-diaminopyrimidine
derivatives were labeled with 18F to study their biological
properties and their potential as positron emission tomography tumor
imaging agents. They inhibited the activity of FAK with IC50 values in the wide range of 0.6–2164 nM, among which the
IC50 of Q6 was 3.2 nM. For the biodistribution
in S180-bearing mice, the corresponding [
18
F]Q6 was relatively good, with the highest uptake
of 3.35 ± 0.32 % ID/g at 30 min postinjection, with a tumor/muscle
ratio of 2.08 and a tumor/bone ratio of 2.48. Accordingly, [
18
F]Q6 was considered as a potential
PET imaging agent for tumor diagnosis.
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