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Biomaterials Science May 2021Drug-resistant pathogens are less sensitive to traditional antibiotics in many stubborn infections. It is imminently desirable to have an effective alternative...
Drug-resistant pathogens are less sensitive to traditional antibiotics in many stubborn infections. It is imminently desirable to have an effective alternative therapeutic agent for combating drug-resistant pathogen infections. Herein, a photo-triggered multifunctional nanoplatform (TMOB/FLU@PCM NPs) with efflux pump and heat shock protein expression reversal activity is developed for the highly effective eradication of drug-resistant fungi. Upon 808 nm laser excitation, the hyperthermia originating from a BODIPY derivative (TMOB) can not only melt the phase-change material (PCM) vehicle consisting of hexadecanol and cis-2-dodecenoic acid (BDSF) to on-demand release the quorum sensing molecule BDSF and the antifungal drug fluconazole (FLU), but can also destroy the integrity of the C. albicans cell membrane. Thanks to the release of BDSF from TMOB/FLU@PCM NPs, the expression of drug efflux pumps (MDR1, CDR2, CDR4) and thermotolerant proteins (HSP12, HSP21, HSP60, HSP90) is inhibited, which further boosts the therapeutic effect of chemo/photothermal therapy. Moreover, the hyphal and biofilm formation of C. albicans can be blocked by TMOB/FLU@PCM NPs under 808 nm laser irradiation. In vitro and in vivo results indicate that TMOB/FLU@PCM NPs with good biosafety can efficiently eliminate clinical azole-resistant C. albicans. Thus, TMOB/FLU@PCM NPs exhibits a promising future in the treatment of azole-resistant C. albicans infection.
Topics: Antifungal Agents; Candida albicans; Fluconazole; Heat-Shock Proteins
PubMed: 33861264
DOI: 10.1039/d1bm00457c -
Journal of Separation Science Oct 2020A simple, rapid, and cost-effective process for the separation of an active anticoagulant fraction from the aqueous fruit extract of Momordica charantia by using rice...
A simple, cost-effective, and rapid separation process for the isolation of anticoagulant active fraction from the fruit extract of Momordica charantia: Characterization of bioactive components and anticoagulant mechanism of active fraction in a mouse model.
A simple, rapid, and cost-effective process for the separation of an active anticoagulant fraction from the aqueous fruit extract of Momordica charantia by using rice husk as adsorbed is described. The in vitro anticoagulant activity of active anticoagulant fraction was comparable to commercial anticoagulants heparin and warfarin. Phytochemical analysis revealed the presence of alkaloids, flavonoids, and phytols in the active anticoagulant fraction, nevertheless; it was devoid of glycosides, triterpenoids, tannins, saponins, steroids, and carbohydrates. By gas chromatography with mass spectrometry analysis, decanoic acid, 1,2,3-propanetriyl ester (22.3%), dodecanoic acid, 1,2,3-propanetriyl ester-d5 (17.3%), dodecenoic acid, 1,2,3-propanetriyl ester (12.5%), and 4-B-methylandrostane 2,3-diol-1,17-dione (11.4%) were identified as the most abundant constituents of active anticoagulant fraction. Presence of αβ-fibrinogenase enzyme was identified by biochemical assay but not by liquid chromatography with tandem mass spectrometry analysis suggesting presence of a novel protease enzyme in this fraction. The active anticoagulant fraction demonstrated biding to fibrinogen but not to thrombin or Factor Xa, inhibited the collagen/ADP-induced mammalian platelet aggregation, showed in vitro thrombolytic activity, noncytotoxic to mammalian cells, showed in vivo plasma defibrinogenation and anticoagulant activities, and inhibited k-carrageen-induced thrombus formation in the tails of mice. Therefore, active anticoagulant fraction (an herbal drug) may find therapeutic application for the prevention and/or treatment of hyperfibrinogenemia/thrombosis-associated cardiovascular disorders.
Topics: Animals; Anticoagulants; Chondrus; Disease Models, Animal; Fruit; Humans; Mice; Momordica charantia; Plant Extracts; Thrombosis
PubMed: 32833304
DOI: 10.1002/jssc.202000452 -
Microbiological Research Nov 2019The in vitro inhibition of quorum sensing signal, xanthan gum secretion, biofilm formation in different Xanthomonas pathovars and biological control of bacterial blight...
The in vitro inhibition of quorum sensing signal, xanthan gum secretion, biofilm formation in different Xanthomonas pathovars and biological control of bacterial blight of rice by the two bioactive extrolites produced by Pseudomonas aeruginosa strain CGK-KS-1 were explored. These extrolites were extracted from Diaion HP-20 resin with methanol and purified by preparative-thin layer chromatography. Further, spectroscopic structural elucidation revealed the tentative identity of these extrolites to be (R,3E,5E,9Z,11E)-13-((3S,5R)-5-acetyl-2,6-dimethylheptan-3-yl)-10-hydroxy-4-methyl-1,8-diazabicyclo[9.3.1]pentadeca-3,5,9,11(15),13-pentaen-2-one and (R,3E,5E,8E,11E)-13-((3S,5R)-5-acetyl-2,6-dimethylheptan-3-yl)-4-methyl-1,8-diazabicyclo[9.3.1]pentadeca-3,5,8,11(15),13-pentaene-2,10-dione, named as Chumacin-1 and Chumacin-2, respectively. Antimicrobial assay showed Chumacin-1 and Chumacin-2 exhibited a strong in vitro growth inhibition against various Xanthomonas pathovars. Quorum sensing overlay assay using a reporter strain Chromobacterium violaceum strain CV026 showed that Chumacin-1 and Chumacin-2 inhibited quorum sensing signaling. The mechanistic studies revealed that these extrolites inhibited the production of quorum sensing signaling factor, cis-11-methyl-2-dodecenoic acid; suppressed the xanthan gum secretion and also inhibited the biofilms formed by various Xanthomonas pathovars. Both Chumacin-1 and Chumacin-2 showed ROS generation in the test Xanthomonas strains, resulting in in vitro cell membrane damage was revealed through CSLM and FE-SEM micrographs. Further, greenhouse experiments using Samba Mashuri (BPT-5204) revealed that seed treatment with Chumacin-1 and Chumacin-2 along with foliar spray groups showed up to ˜80% reduction in bacterial blight disease in rice. To the best of our knowledge, this is the first report on new quorum sensing inhibitors, Chumacin-1 and Chumacin-2 produced by Pseudomonas aeruginosa strain CGK-KS-1 exhibiting DSF inhibition activity in Xanthomonas oryzae pv. oryzae.
Topics: Anti-Infective Agents; Biofilms; Biological Control Agents; Chromobacterium; Microbial Sensitivity Tests; Molecular Docking Simulation; Oryza; Plant Diseases; Polysaccharides, Bacterial; Polystyrenes; Pseudomonas aeruginosa; Quorum Sensing; Signal Transduction; Xanthomonas
PubMed: 31422232
DOI: 10.1016/j.micres.2019.126301