OBJECTIVES: Resistance to antibiotics among bacteria of clinical importance, including Staphylococcus aureus, is a serious problem worldwide and the search for alternatives is needed. Some metal complexes have antibacterial properties and when combined with antibiotics, they may increase bacterial sensitivity to antimicrobials. In this study, we synthesized the iron complex and tested it in combination with ampicillin (Fe16 + AMP) against S. aureus. METHODS: An iron complex (Fe16) was synthesized and characterized using spectroscopy methods. Confirmation of the synergistic effect between the iron complex (Fe16) and ampicillin (AMP) was performed using ζ-potential, infrared spectra and FICI index calculated from the minimum inhibitory concentration (MIC) from the checkerboard assay. Cytotoxic properties of combination Fe16 + AMP was evaluated on eukaryotic cell line. Impact of combination Fe16 + AMP on chosen genes of S. aureus were performed by Quantitative Real-Time PCR. RESULTS: The MIC of Fe16 + AMP was significantly lower than that of AMP and Fe16 alone. Furthermore, the infrared spectroscopy revealed the change in the ζ-potential of Fe16 + AMP. We demonstrated the ability of Fe16 + AMP to disrupt the bacterial membrane of S. aureus and that likely allowed for better absorption of AMP. In addition, the change in gene expression of bacterial efflux pumps at the sub-inhibitory concentration of AMP suggests an insufficient import of iron into the bacterial cell. At the same time, Fe16 + AMP did not have any cytotoxic effects on keratinocytes. CONCLUSIONS: Combined Fe16 + AMP therapy demonstrated significant synergistic and antimicrobial effects against S. aureus. This study supports the potential of combination therapy and further research.
- MeSH
- ampicilin farmakologie MeSH
- antibakteriální látky farmakologie MeSH
- lidé MeSH
- methicilin rezistentní Staphylococcus aureus * MeSH
- mikrobiální testy citlivosti MeSH
- stafylokokové infekce * farmakoterapie MeSH
- Staphylococcus aureus MeSH
- synergismus léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The emergence of antibiotic resistance in pathogenic bacteria has become a global threat, encouraging the adoption of efficient and effective alternatives to conventional antibiotics and promoting their use as replacements. Titanium dioxide nanoparticles (TiO2 NPs) have been reported to exhibit antibacterial properties. In this study, we synthesized and characterized TiO2 NPs in anatase and rutile forms with surface modification by geraniol (GER). RESULTS: The crystallinity and morphology of modified TiO2 NPs were analyzed by UV/Vis spectrophotometry, X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) with elemental mapping (EDS). The antimicrobial activity of TiO2 NPs with geraniol was assessed against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli. The minimum inhibitory concentration (MIC) values of modified NPs ranged from 0.25 to 1.0 mg/ml against all bacterial strains, and the live dead assay and fractional inhibitory concentration (FIC) supported the antibacterial properties of TiO2 NPs with GER. Moreover, TiO2 NPs with GER also showed a significant decrease in the biofilm thickness of MRSA. CONCLUSIONS: Our results suggest that TiO2 NPs with GER offer a promising alternative to antibiotics, particularly for controlling antibiotic-resistant strains. The surface modification of TiO2 NPs by geraniol resulted in enhanced antibacterial properties against multiple bacterial strains, including antibiotic-resistant MRSA. The potential applications of modified TiO2 NPs in the biomedical and environmental fields warrant further investigation.
Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST); that is, they form phase-separated aggregates when heated above a threshold temperature. Such polymers found many promising (bio)medical applications, including in situ thermogelling with controlled drug release, polymer-supported radiotherapy (brachytherapy), immunotherapy, and wound dressing, among others. Yet, despite the extensive research on medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remained unknown. Thus, herein, they studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots that subsequently dissolved with a two-phase kinetics (depot maturation, slow redissolution) with half-lives 2 weeks to 5 months, as depot vitrification prolonged their half-lives. Additionally, the decrease of TCP of a polymer solution increased the density of the intramuscular depot. Moreover, they detected secondary polymer depots in the kidneys and liver; these secondary depots also followed two-phase kinetics (depot maturation and slow dissolution), with half-lives 8 to 38 days (kidneys) and 15 to 22 days (liver). Overall, these findings may be used to tailor the properties of thermoresponsive polymers to meet the demands of their medicinal applications. Their methods may become a benchmark for future studies of polymer biodistribution.
- MeSH
- myši MeSH
- polymery * MeSH
- teplota MeSH
- tkáňová distribuce MeSH
- uvolňování léčiv MeSH
- voda * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Strains P8930T and 478 were isolated from Antarctic glaciers located on James Ross Island and King George Island, respectively. They comprised Gram-stain-negative short rod-shaped cells forming pink pigmented colonies and exhibited identical 16S rRNA gene sequences and highly similar MALDI TOF mass spectra, and hence were assigned as representatives of the same species. Phylogenetic analysis based on 16S rRNA gene sequences assigned both isolates to the genus Pedobacter and showed Pedobacter frigidisoli and Pedobacter terrae to be their closest phylogenetic neighbours, with 97.4 and 97.2 % 16S rRNA gene sequence similarities, respectively. These low similarity values were below the threshold similarity value of 98.7%, confirming the delineation of a new bacterial species. Further genomic characterization included whole-genome sequencing accompanied by average nucleotide identity (ANI) and digital DNA-DNA hybridization calculations, and characterization of the genome features. The ANI values between P8930T and P. frigidisoli RP-3-11T and P. terrae DSM 17933T were 79.7 and 77.6 %, respectively, and the value between P. frigidisoli RP-3-11T and P. terrae DSM 17933T was 77.7 %, clearly demonstrating the phylogenetic distance and the novelty of strain P8930T. Further characterization included analysis of cellular fatty acids, quinones and polar lipids, and comprehensive biotyping. All the obtained results proved the separation of strains P8930T and 478 from the other validly named Pedobacter species, and confirmed that they represent a new species for which the name Pedobacter fastidiosus sp. nov. is proposed. The type strain is P8930T (=CCM 8938T=LMG 32098T).
- MeSH
- DNA bakterií genetika MeSH
- ekosystém MeSH
- fylogeneze MeSH
- mastné kyseliny chemie MeSH
- Pedobacter * MeSH
- RNA ribozomální 16S genetika MeSH
- sekvenční analýza DNA MeSH
- techniky typizace bakterií MeSH
- zastoupení bazí MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Antarktida MeSH
Purpose: The present study deals with the in vitro evaluation of the potential use of coordination compound-based zinc oxide (ZnO) nanoparticles (NPs) for the treatment of triple negative breast cancer cells (TNBrCa). As BrCa is one of the most prevalent cancer types and TNBrCa treatment is difficult due to poor prognosis and a high metastasis rate, finding a more reliable treatment option should be of the utmost interest. Methods: Prepared by reacting zinc carboxylates (formate, acetate, propionate, butyrate, isobutyrate, valerate) and hexamethylenetetramine, 4 distinct coordination compounds were further subjected to two modes of conversion into ZnO NPs - ultrasonication with oleic acid or heating of pure precursors in an air atmosphere. After detailed characterization, the resulting ZnO NPs were subjected to in vitro testing of cytotoxicity toward TNBrCa and normal breast epithelial cells. Further, their biocompatibility was evaluated. Results: The resulting ZnO NPs provide distinct morphological features, size, biocompatibility, and selective cytotoxicity toward TNBrCa cells. They internalize into two types of TNBrCa cells and imbalance their redox homeostasis, influencing their metabolism, morphology, and ultimately leading to their death via apoptosis or necrosis. Conclusion: The crucial properties of ZnO NPs seem to be their morphology, size, and zinc content. The ZnO NPs with the most preferential values of all three properties show great promise for a future potential use in the therapy of TNBrCa.
- MeSH
- antitumorózní látky chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nanočástice chemie MeSH
- oxid zinečnatý chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- triple-negativní karcinom prsu patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
We present a novel series of radioiodinated tracers and potential theranostics for diseases accompanied by pathological function of proteins involved in choline transport. Unlike choline analogues labeled with 11C or 18F that are currently used in the clinic, the iodinated compounds described herein are applicable in positron emission tomography, single-photon emission computed tomography, and potentially in therapy, depending on the iodine isotope selection. Moreover, favorable half-lives of iodine isotopes result in much less challenging synthesis by isotope exchange reaction. Six of the described compounds were nanomolar ligands, and the best compound possessed an affinity 100-fold greater than that of choline. Biodistribution data of 125I-labeled ligands in human prostate carcinoma bearing (PC-3) mice revealed two compounds with a biodistribution profile superior to that of [18F]fluorocholine.
- MeSH
- apoptóza MeSH
- cholin analogy a deriváty farmakokinetika MeSH
- lidé MeSH
- myši SCID MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- nádory prostaty diagnostické zobrazování metabolismus patologie MeSH
- pozitronová emisní tomografie MeSH
- proliferace buněk MeSH
- radioaktivní indikátory * MeSH
- radiofarmaka farmakokinetika MeSH
- radioizotopy fluoru farmakokinetika MeSH
- radioizotopy jodu farmakokinetika MeSH
- tkáňová distribuce MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hemochromatosis (iron overload) encompasses a group of diseases that are characterized by a toxic hyperaccumulation of iron in parenchymal organs. Currently, only few treatments for this disease have been approved; however, all these treatments possess severe side effects. In this study, a paradigm for hemochromatosis maintenance/preventive therapy is investigated: polymers with negligible systemic biological availability form stable complexes with iron ions in the gastrointestinal tract, which reduces the biological availability of iron. Macroporous polymer beads are synthesized with three different iron-chelating moieties (benzene-1,2-diol, benzene-1,2,3-triol, and 1,10-phenanthroline). The polymers rapidly chelate iron ions from aqueous solutions in vitro in the course of minutes, and are noncytotoxic and nonprooxidant. Moreover, the in vivo biodistribution and pharmacokinetics show a negligible uptake from the gastrointestinal tract (using 125 I-labeled polymer and single photon emission computed tomography/computed tomography), which generally prevents them from having systemic side effects. The therapeutic efficacy of the prepared polymers is successfully tested in vivo, and exhibits a significant inhibition of iron uptake from the gastrointestinal tract without any noticeable signs of toxicity. Furthermore, an in silico method is developed for the prediction of chelator selectivity. Therefore, this paradigm can be applied to the next-generation maintenance/preventive treatment for hemochromatosis and/or other diseases of similar pathophysiology.
- MeSH
- benzen chemie farmakologie MeSH
- chelátory železa chemie farmakologie MeSH
- fenantroliny chemie farmakologie MeSH
- gastrointestinální trakt účinky léků MeSH
- hemochromatóza diagnostické zobrazování farmakoterapie patologie MeSH
- lidé MeSH
- polymery chemie farmakologie MeSH
- teoretické modely * MeSH
- tomografie emisní počítačová MeSH
- železo metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Magnetic resonance imaging (MRI) using 19F-based tracers has emerged as a promising multi-purpose noninvasive diagnostic tool and its application requires the use of various 19F-based tracers for the intended diagnostic purpose. In this study, we report a series of double-stimuli-responsive polymers for use as injectable implants, which were designed to form implants under physiological conditions, and to subsequently dissolve with different dissolution rates (t1/2 ranges from 30 to more than 250 days). Our polymers contain a high concentration of fluorine atoms, providing remarkable signal detectability, and both a hydrophilic monomer and a pH-responsive monomer that alter the biodistribution properties of the implant. The implant location and dissolution were observed using 19F MRI, which allows the anatomic extent of the implant to be monitored. The dissolution kinetics and biocompatibility of these materials were thoroughly analyzed. No sign of toxicity in vitro or in vivo or pathology in vivo was observed, even in chronic administration. The clinical applicability of our polymers was further confirmed via imaging of a rat model by employing an instrument currently used in human medicine.
Bacteria of the genus Massilia often colonize extreme ecosystems, however, a detailed study of the massilias from the Antarctic environment has not yet been performed. Here, sixty-four Gram-stain-negative, aerobic, motile rods isolated from different environmental samples on James Ross Island (Antarctica) were subjected to a polyphasic taxonomic study. The psychrophilic isolates exhibited slowly growing, moderately slimy colonies revealing bold pink-red pigmentation on R2A agar. The set of strains exhibited the highest 16S rRNA gene sequence similarities (99.5-99.9%) to Massilia violaceinigra B2T and Massilia atriviolacea SODT and formed several phylogenetic groups based on the analysis of gyrB and lepA genes. Phenotypic characteristics allowed four of them to be distinguished from each other and from their closest relatives. Compared to the nearest phylogenetic neighbours the set of six genome-sequenced representatives exhibited considerable phylogenetic distance at the whole-genome level. Bioinformatic analysis of the genomic sequences revealed a high number of putative genes involved in oxidative stress response, heavy-metal resistance, bacteriocin production, the presence of putative genes involved in nitrogen metabolism and auxin biosynthesis. The identification of putative genes encoding aromatic dioxygenases suggests the biotechnology potential of the strains. Based on these results four novel species and one genomospecies of the genus Massilia are described and named Massilia rubra sp. nov. (P3094T=CCM 8692T=LMG 31213T), Massilia aquatica sp. nov. (P3165T=CCM 8693T=LMG 31211T), Massilia mucilaginosa sp. nov. (P5902T=CCM 8733T=LMG 31210T), and Massilia frigida sp. nov. (P5534T=CCM 8695T=LMG 31212T).
- MeSH
- bakteriální geny MeSH
- DNA bakterií genetika MeSH
- fenotyp MeSH
- fylogeneze MeSH
- genom bakteriální MeSH
- geny rRNA MeSH
- geologické sedimenty mikrobiologie MeSH
- jezera mikrobiologie MeSH
- Oxalobacteraceae klasifikace genetika izolace a purifikace fyziologie MeSH
- řeky mikrobiologie MeSH
- RNA ribozomální 16S genetika MeSH
- sekvenční analýza DNA MeSH
- techniky typizace bakterií MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Antarktida MeSH
A taxonomic study was carried out on four Gram-stain-negative strains P5773T, P6169, P4708 and P6245, isolated from anus or mouth samples of Weddell seals at James Ross Island, Antarctica. The results of initial 16S rRNA gene sequence analysis showed that all four strains formed a group placed in the genus Pseudomonas and found Pseudomonas guineae and Pseudomonas peli to be their closest neighbours with 99.9 and 99.2 % sequence similarity, respectively. Sequence analysis of rpoD, rpoB and gyrB housekeeping genes confirmed the highest similarity of isolates to P. peli (rpoD) and to P. guineae (rpoB and gyrB). The average nucleotide identity value below 86 %, as calculated from the whole-genome sequence data, showed the low genomic relatedness of P5773T to its phylogenetic neighbours. The complete genome of strain P5773T was 4.4 Mb long and contained genes encoding proteins with biotechnological potential. The major fatty acids of the seal isolates were summed feature 8 (C18 : 1ω7c), summed feature 3 (C16 : 1ω7c/C16 : 1ω6c) and C16:0. The major respiratory quinone was Q9. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Putrescine and spermidine are predominant in the polyamine pattern. Further characterization performed using repetitive sequence-based PCR fingerprinting and MALDI-TOF MS analysis showed that the studied isolates formed a coherent cluster separated from the remaining Pseudomonas species and confirmed that they represent a novel species within the genus Pseudomonas, for which the name Pseudomonasleptonychotis sp. nov. is suggested. The type strain is P5773T (=CCM 8849T=LMG 30618T).
- MeSH
- bakteriální geny MeSH
- DNA bakterií genetika MeSH
- fosfolipidy chemie MeSH
- fylogeneze * MeSH
- mastné kyseliny chemie MeSH
- Pseudomonas klasifikace MeSH
- RNA ribozomální 16S genetika MeSH
- sekvenční analýza DNA MeSH
- techniky typizace bakterií MeSH
- tuleňovití mikrobiologie MeSH
- ubichinon chemie MeSH
- zastoupení bazí MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Antarktida MeSH
