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1.
Sci Rep ; 11(1): 16858, 2021 08 19.
Article in English | MEDLINE | ID: mdl-34413439

ABSTRACT

The effect of nanobubbles on anaerobic growth and metabolism of Pseudomonas aeruginosa was investigated. P. aeruginosa grew earlier in the culture medium containing nanobubbles and the bacterial cell concentration in that culture medium was increased a few times higher compared to the medium without nanobubbles under anaerobic condition. Both gas and protein, which are the metabolites of P. aeruginosa, were remarkably produced in the culture medium containing nanobubbles whereas those metabolites were little detected in the medium without nanobubbles, indicating nanobubbles activated anaerobic growth and metabolism of P. aeruginosa. The carbon dioxide nanobubbles came to be positively charged by adsorbing cations and delivered ferrous ions, one of the trace essential elements for bacterial growth, to the microbial cells, which activated the growth and metabolism of P. aeruginosa. The oxygen nanobubbles activated the activities of P. aeruginosa as an oxygen source.


Subject(s)
Nanoparticles/chemistry , Pseudomonas aeruginosa/growth & development , Pseudomonas aeruginosa/metabolism , Anaerobiosis/drug effects , Culture Media/pharmacology , Sterilization
2.
Bioorg Chem ; 107: 104627, 2021 02.
Article in English | MEDLINE | ID: mdl-33476868

ABSTRACT

One compound sometimes shows two biological functions, becoming important aspect of recent drug discovery. This study began with an attempt to confirm the previously reported molecular mechanism of the anti-human immunodeficiency virus (HIV) heterocyclic compound BMMP [2-(benzothiazol-2-ylmethylthio)-4-methylpyrimidine], i.e., induction of abnormal uncoating of the viral core at the post-entry step. Our mechanistic study gave results consistent with this mechanism. We further attempted to find out the molecular target of BMMP by a pulldown approach using previously synthesized biotinylated BMMP (Biotin-BMMP) and successfully identified heterogenous nuclear ribonucleoprotein M (hnRNP M) as a BMMP-binding protein. This protein was found not to be accountable for the anti-HIV activity of BMMP. As hnRNP M has been reported to promote cancer metastasis, we tested this mechanism and found that BMMP suppressed migration of the human lung carcinoma cell line A549 stimulated with transforming growth factor-ß (TGF-ß). Mechanistic study showed that BMMP suppressed the expression of CD44 mRNA via the regulation of hnRNP M. Furthermore, six new derivatives of BMMP were synthesized, and the patterns of their activities against HIV-1 and cell migration were not uniform, suggesting that the anti-HIV mechanism and the anti-cell migration mechanism of BMMP are independent. Taken together, the anti-cell migration activity of the anti-HIV heterocyclic compound BMMP was newly discovered by identification of its binding protein hnRNP M using a chemical biology approach.


Subject(s)
Anti-HIV Agents/chemistry , Heterocyclic Compounds/chemistry , Heterogeneous-Nuclear Ribonucleoprotein Group M/metabolism , Anti-HIV Agents/metabolism , Anti-HIV Agents/pharmacology , Cell Line , Cell Movement/drug effects , Down-Regulation/drug effects , Drug Evaluation, Preclinical , Heterocyclic Compounds/metabolism , Heterocyclic Compounds/pharmacology , Heterogeneous-Nuclear Ribonucleoprotein Group M/antagonists & inhibitors , Heterogeneous-Nuclear Ribonucleoprotein Group M/genetics , Humans , Hyaluronan Receptors/genetics , Hyaluronan Receptors/metabolism , Protein Binding , Pyrimidines/chemistry , Pyrimidines/metabolism , Pyrimidines/pharmacology , RNA Interference , RNA, Small Interfering/chemistry , RNA, Small Interfering/metabolism
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