Quorum sensing is one kind of cell-to-cell signalling system among microorganisms that works in response to their population density via autoinducers exemplified by AHL and oligopeptides. In this study, fourteen AHL d...Quorum sensing is one kind of cell-to-cell signalling system among microorganisms that works in response to their population density via autoinducers exemplified by AHL and oligopeptides. In this study, fourteen AHL derivatives were synthesised by a chemical synthesis method, and two types of AHL derivatives were measured and screened by crystal violet staining assay, which have more obvious inhibitory effects on A. ferrooxidans biofilms under arsenic environment. Their structures were verified through IR and NMR identification. The morphological changes of A. ferrooxidans under the influence of the AHL derivatives were compared. In addition, the effects of AHL derivatives(0.1 μg/mL and 1 μg/mL) on membrane formation of A. ferrooxidans under high concentration of arsenic resistance(1,600 mg/L) were explored. Solid experimental data firstly showed that a portion of logarithmic microorganisms were ruptured under the effect of high arsenic concentration. Secondly, the volume of the cell shrank and the number of extracellular polymeric substances decreased after the addition of the AHL derivatives at high concentrations. Therefore, we found here that two derivatives used at concentrations of 0.1 μg/mL and 1 μg/m L accompanied with high concentration of arsenic can both effectively restrict biofilms formation by A. ferrooxidans.展开更多
OBJECTIVE To investigate the pharmacological effect of a plant sesquiterpene lactone(designated D)and its semi-organically synthesized novel derivative(designated S)and the role of lipid mediators,viz.,oxylipins in at...OBJECTIVE To investigate the pharmacological effect of a plant sesquiterpene lactone(designated D)and its semi-organically synthesized novel derivative(designated S)and the role of lipid mediators,viz.,oxylipins in attenuating vemurafenib-induced cutaneous side effects.METHODS A DMBA/TPAinduced skin carcinogenesis mouse model mimicking cutaneous side effect caused by vemurafenib was established to evaluate the efficacy of compound D and S in reversal of vemurafenib side effect.Comparative oxylipin metabolomics platform using UPLC-TQD mass spectrometry coupled with partial least squares-discriminant analysis(PLS-DA)analysis,cell-based assays,and immunochemistry analysis were performed to elucidate the mechanism insights of DET and S compounds and the role of specific oxylipins in skin cancer carcinogenesis.RESULTS Vemurafenib treatment expedited the skin papillomas formation in DMBA-TPA treated mouse from week 6 to week 3.Both D and S compounds could suppress the vemurafenib side effect and also decrease total papillomas numbers(55% to 72%)and average sizes(66% to 89%).Oxylipins metabolome analysis shows that specific arachidonic acid metabolites may play a role in vemurafenib-induced squamous cell carcinoma or keratoacanthomas formation in mouse skin that can be deregulated by D or S compound treatment.Notably,S compound can inhibit vemurafenib-induced paradoxical activation of MAP kinases in mouse skin or in NRAS mutant melanoma cells.CONCLUSION Our results indicate that plant sesquiterpene lactone D and its novel analog can reduce cutaneous side effect of vemurafenib through novel modes of action by inhibiting paradoxical activation of MAP kinases and de-regulating pro-inflammation mediators COX-2 and specific ecosanoid-type of oxylipins.This study may suggest a novel adjuvant therapy approach in treatment of BRAFV600 Emutant melanoma.展开更多
基金Project(31660026)supported by the National Natural Science Foundation of ChinaProject(lzujbky-2016-152)supported by the National Basic Research Program of China
文摘Quorum sensing is one kind of cell-to-cell signalling system among microorganisms that works in response to their population density via autoinducers exemplified by AHL and oligopeptides. In this study, fourteen AHL derivatives were synthesised by a chemical synthesis method, and two types of AHL derivatives were measured and screened by crystal violet staining assay, which have more obvious inhibitory effects on A. ferrooxidans biofilms under arsenic environment. Their structures were verified through IR and NMR identification. The morphological changes of A. ferrooxidans under the influence of the AHL derivatives were compared. In addition, the effects of AHL derivatives(0.1 μg/mL and 1 μg/mL) on membrane formation of A. ferrooxidans under high concentration of arsenic resistance(1,600 mg/L) were explored. Solid experimental data firstly showed that a portion of logarithmic microorganisms were ruptured under the effect of high arsenic concentration. Secondly, the volume of the cell shrank and the number of extracellular polymeric substances decreased after the addition of the AHL derivatives at high concentrations. Therefore, we found here that two derivatives used at concentrations of 0.1 μg/mL and 1 μg/m L accompanied with high concentration of arsenic can both effectively restrict biofilms formation by A. ferrooxidans.
基金The project supported by a research grant from Ministry of Science and Technology(MOST 103-2320-B-001-008-MY3),Chinese Taipei
文摘OBJECTIVE To investigate the pharmacological effect of a plant sesquiterpene lactone(designated D)and its semi-organically synthesized novel derivative(designated S)and the role of lipid mediators,viz.,oxylipins in attenuating vemurafenib-induced cutaneous side effects.METHODS A DMBA/TPAinduced skin carcinogenesis mouse model mimicking cutaneous side effect caused by vemurafenib was established to evaluate the efficacy of compound D and S in reversal of vemurafenib side effect.Comparative oxylipin metabolomics platform using UPLC-TQD mass spectrometry coupled with partial least squares-discriminant analysis(PLS-DA)analysis,cell-based assays,and immunochemistry analysis were performed to elucidate the mechanism insights of DET and S compounds and the role of specific oxylipins in skin cancer carcinogenesis.RESULTS Vemurafenib treatment expedited the skin papillomas formation in DMBA-TPA treated mouse from week 6 to week 3.Both D and S compounds could suppress the vemurafenib side effect and also decrease total papillomas numbers(55% to 72%)and average sizes(66% to 89%).Oxylipins metabolome analysis shows that specific arachidonic acid metabolites may play a role in vemurafenib-induced squamous cell carcinoma or keratoacanthomas formation in mouse skin that can be deregulated by D or S compound treatment.Notably,S compound can inhibit vemurafenib-induced paradoxical activation of MAP kinases in mouse skin or in NRAS mutant melanoma cells.CONCLUSION Our results indicate that plant sesquiterpene lactone D and its novel analog can reduce cutaneous side effect of vemurafenib through novel modes of action by inhibiting paradoxical activation of MAP kinases and de-regulating pro-inflammation mediators COX-2 and specific ecosanoid-type of oxylipins.This study may suggest a novel adjuvant therapy approach in treatment of BRAFV600 Emutant melanoma.
