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ChemMedChem Jun 2024Intending to homogenize the biological activities of both quinoxaline and imidazole moieties, the proligand, 1-methyl-3-quinoxaline-imidazolium hexaflurophosphate...
Design, Synthesis and Bioactivity Evaluation of Ag(I)-, Au(I)- and Au(III)-Quinoxaline-Wingtip N-Heterocyclic Carbene Complexes Against Antibiotic Resistant Bacterial Pathogens.
Intending to homogenize the biological activities of both quinoxaline and imidazole moieties, the proligand, 1-methyl-3-quinoxaline-imidazolium hexaflurophosphate (1.HPF6), and [Ag(1)2][PF6], (2); [Au(1)2][PF6], (3); and [Au(1)Cl3], (4) NHC complexes were synthesized. All the synthesized compounds were characterized by elemental analysis, NMR, and UV-Vis spectroscopy. Finally, single crystal X-ray structures revealed a linear geometry for complex 2 whereas a square planar geometry for complex 4. The formation of complex 3 was confirmed and supported by its MS spectra. The antibacterial activities of all the synthesized complexes were investigated against gram-positive bacteria and gram-negative bacteria. The Au(III)-NHC complex, 4 showed the highest antibacterial activity with extremely low MIC values against both the bacterial strains (0.24 µg.mL-1). Monitoring of zeta potential supports the higher activity of complex 4 compared to 2 and 3. ROS production by complex 4 has also been measured in vitro in the CT26 cancer cell lines, which is directly responsible for targetting and killing the bacterial pathogens. Cell cytotoxicity assay using 293T cell lines has been performed to investigate the biocompatibility nature of complex 4. Also, an excellent hemocompatibility was assigned to it from its hemolytic studies, which provide valuable insights into the design of novel antibacterial agents.
PubMed: 38934210
DOI: 10.1002/cmdc.202400236 -
Heliyon Jun 2024Current biofilm modelling of the opportunistic pathogen, (PA) in people with cystic fibrosis (PwCF) is limited in its ability to mimic the complexities of the cystic...
Current biofilm modelling of the opportunistic pathogen, (PA) in people with cystic fibrosis (PwCF) is limited in its ability to mimic the complexities of the cystic fibrosis (CF) lung environment. Recent adaptations of the Microbial Identification after Passive CLARITY Technique (MiPACT) in CF research have allowed for the direct imaging of PA biofilm spatial organization and structure in expectorated sputum. Here, we performed a comparative analysis of and within patient () measures of PA biofilms using sputa from new onset infected children with CF. MiPACT-fluorescent hybridization (FISH) and fluorescent anti-Psl monoclonal antibody (mAb) staining was performed to directly visualize PA and Psl (exopolysaccharide in PA biofilm matrix) in 11 CF sputum specimens. Corresponding PA isolates, recovered from the same sputum samples, were grown as biofilms in a glass slide chamber model, then visualized by fluorescent live-cell and anti-Psl mAb staining. We observed that PA biovolume, aggregation and Psl antibody binding (normalized per PA biovolume) in CF sputum did not correlate with the model, although a trend towards significance in the biovolume relationship was observed with the addition of sputum supernatant to the model.
PubMed: 38933957
DOI: 10.1016/j.heliyon.2024.e32424 -
Open Forum Infectious Diseases Jun 2024
PubMed: 38933740
DOI: 10.1093/ofid/ofae258 -
Materials Today. Bio Jun 2024Burns represent a prevalent global health concern and are particularly susceptible to bacterial infections. Severe infections may lead to serious complications, posing a...
Burns represent a prevalent global health concern and are particularly susceptible to bacterial infections. Severe infections may lead to serious complications, posing a life-threatening risk. Near-infrared (NIR)-assisted photothermal antibacterial combined with antioxidant hydrogel has shown significant potential in the healing of infected wounds. However, existing photothermal agents are typically metal-based, complicated to synthesize, or pose biosafety hazards. In this study, we utilized plant-derived blackcurrant extract (B) as a natural source for both photothermal and antioxidant properties. By incorporating B into a G-O hydrogel crosslinked through Schiff base reaction between gelatin (G) and oxidized pullulan (O), the resulting G--B hydrogel exhibited good injectability and biocompatibility along with robust photothermal and antioxidant activities. Upon NIR irradiation, the controlled temperature (around 45-50 °C) generated by the G--B hydrogel resulted in rapid (10 min) and efficient killing of (99 %), (98 %), and (82 %). Furthermore, the G--B hydrogel containing 0.5 % blackcurrant extract promoted collagen deposition, angiogenesis, and accelerated burn wound closure conclusively, demonstrating that this well-designed and extract-contained hydrogel dressing holds immense potential for enhancing the healing process of bacterial-infected burn wounds.
PubMed: 38933414
DOI: 10.1016/j.mtbio.2024.101113 -
Viruses May 2024Bacteriophages (phages) are viruses that infect the bacteria within which their reproduction cycle takes place, a process that ends in the lysis and death of the...
Bacteriophages (phages) are viruses that infect the bacteria within which their reproduction cycle takes place, a process that ends in the lysis and death of the bacterial cell. Some phages are also able to destroy bacterial biofilms. Due to increased antibiotics resistance, , another biofilm-forming pathogen, is a problem in many parts of the world. Zinc oxide (ZnO) and other metal nanoparticles (NPs) are biologically active and also possess anti-biofilm properties. ZnO-NPs were prepared by the green synthesis method using orange peels. The vibrational peaks of the ZnO-NPs were analyzed using FTIR analysis, and their size and morphological properties were determined using scanning electron microscopy (SEM). The ability of the ZnO-NPs to reduce or eliminate biofilm alone or in combination with phages PB10 and PA19 was investigated. The cells were effectively killed in the preformed 48 h biofilms during a 24 h incubation with the ZnO-NP-phage combination, in comparison with the control or ZnO-NPs alone. The treatments on growing biofilms were most efficient in the final stages of biofilm development. All five treatment groups showed a significant biofilm reduction compared to the control group ( < 0.0001) at 48 h of incubation. The influence of the ZnO-NPs and phages on the quorum sensing system of was monitored by quantitative real-time PCR (qRT-PCR) of the autoinducer biosynthesis gene . While the ZnO-NPs repressed the gene transcription, the phages slightly activated it at 24 and 48 h of incubation. Also, the effect of the ZnO-NPs and phage PA19 on the viability of HFF2 cells was investigated and the results showed that the combination of NPs with PA19 reduced the toxic effect of ZnO-NPs and also stimulated the growth in normal cells.
Topics: Zinc Oxide; Pseudomonas aeruginosa; Biofilms; Metal Nanoparticles; Green Chemistry Technology; Bacteriophages; Anti-Bacterial Agents; Nanoparticles
PubMed: 38932188
DOI: 10.3390/v16060897 -
Pharmaceutics May 2024The increasing prevalence of diabetic wounds presents a significant challenge due to the difficulty of natural healing and various obstacles. (DB) and (AT) are well...
The increasing prevalence of diabetic wounds presents a significant challenge due to the difficulty of natural healing and various obstacles. (DB) and (AT) are well recognized for their potent healing abilities, which include potent antibacterial and anti-inflammatory activities. In this study, electrospun nanofibers (NFs) based on polyvinyl pyrrolidone (PVP) were co-loaded with both DB and AT, aiming to magnify their efficacy as wound-dressing applications for diabetic wound healing. The evaluation of these NFs as wound dressings was conducted using a streptozotocin-induced diabetic rat model. Electrospun NFs were prepared using the electrospinning of the PVP polymer, resulting in nanofibers with consistent, smooth surfaces. The loading capacity (LC) of AT and DB into NFs was 64.1 and 70.4 µg/mg, respectively, while in the co-loaded NFs, LC was 49.6 for AT and 57.2 µg/mg for DB. In addition, X-ray diffraction (XRD) revealed that DB and AT were amorphously dispersed within the NFs. The loaded NFs showed a dissolution time of 30 s in PBS (pH 7.4), which facilitated the release of AT and DB (25-38% after 10 min), followed by a complete release achieved after 180 min. The antibacterial evaluation demonstrated that the DB-AT mixture had potent activity against () and (). Along with that, the DB-AT NFs showed effective growth inhibition for both and compared to the control NFs. Moreover, wound healing was evaluated in vivo in diabetic Wistar rats over 14 days. The results revealed that the DB-AT NFs improved wound healing within 14 days significantly compared to the other groups. These results highlight the potential application of the developed DB-AT NFs in wound healing management, particularly in diabetic wounds.
PubMed: 38931828
DOI: 10.3390/pharmaceutics16060704 -
Pharmaceutics May 2024Skin lesions are an important health concern, exposing the body to infection risks. Utilizing natural products containing chamomile ( L.) holds promise for curative...
Skin lesions are an important health concern, exposing the body to infection risks. Utilizing natural products containing chamomile ( L.) holds promise for curative purposes. Additionally, hyaluronic acid (HA), an active ingredient known for its tissue regeneration capacity, can expedite healing. In this study, we prepared and characterized an extract of and integrated it into a nanoemulsion system stabilized with HA, aiming at harnessing its healing potential. We assessed the impact of alcoholic strength on flavonoid extraction and chemically characterized the extract using UHPLC/MS while quantifying its antioxidant and antimicrobial capacity. We developed a nanoemulsion loaded with extract and evaluated the effect of HA stabilization on pH, droplet size, polydispersity index (PDI), zeta potential, and viscosity. Results indicated that 70% hydroalcoholic extraction yielded a higher flavonoid content. The extract exhibited antioxidant capacity in vitro, a desirable trait for skin regeneration, and demonstrated efficacy against key microbial strains (, , , and ) associated with skin colonization and infections. Flavonoids spireoside and apiin emerged as the most abundant bioactives. The addition of HA led to increased viscosity while maintaining a suitable pH for topical application. Zeta potential, droplet size, and PDI met acceptable criteria. Moreover, incorporating extract into the nanoemulsion enhanced its antimicrobial effect. Hence, the nanoemulsion system loaded with and HA stabilization exhibits favorable characteristics for topical application, showing promise in aiding the healing processes.
PubMed: 38931825
DOI: 10.3390/pharmaceutics16060701 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Due to its rapid resistance development and ability to form biofilms, treatment of infections is becoming more complicated by the day. Drug combinations may help reduce...
BACKGROUND
Due to its rapid resistance development and ability to form biofilms, treatment of infections is becoming more complicated by the day. Drug combinations may help reduce both resistance and biofilm formation.
METHODS
Using the microtiter plate assay, we investigated the in vitro inhibition of biofilm formation and the disruption of preformed biofilms in multidrug-resistant and extensively drug-resistant clinical isolates of in the presence of peak plasma levels of eight antipseudomonal antibiotics alone and in combination with fosfomycin: ceftazidime, piperacillin/tazobactam, cefepime, imipenem, gentamicin, amikacin, ciprofloxacin and colistin.
RESULTS
Combination therapy was significantly superior to monotherapy in its inhibition of biofilm formation. The highest inhibition rates were observed for combinations with colistin, cefepime and ceftazidime.
CONCLUSION
Our results support fosfomycin combination therapy as an enhanced prophylactic option. Moreover, combinations with β-lactam antibiotics and colistin demonstrated a more potent inhibition effect on biofilm formation than protein synthesis inhibitors.
PubMed: 38931436
DOI: 10.3390/ph17060769 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Bee-collected pollen (BCP) and bee bread (BB) are honey bee products known for their beneficial biological properties. The main goal of this study was to investigate BB...
Bee-collected pollen (BCP) and bee bread (BB) are honey bee products known for their beneficial biological properties. The main goal of this study was to investigate BB microbiota and its contribution to bioactivity exerted by BB. The microbiota of BB samples collected at different maturation stages was investigated via culture-independent (Next Generation Sequencing, NGS) and culture-dependent methods. Microbial communities dynamically fluctuate during BB maturation, ending in a stable microbial community structure in mature BB. Bee bread bacterial isolates were tested for phenotypes and genes implicated in the production and secretion of enzymes as well as antibacterial activity. Out of 309 bacterial isolates, 41 secreted hemicellulases, 13 cellulases, 39 amylases, 132 proteinases, 85 Coomassie brilliant blue G or R dye-degrading enzymes and 72 Malachite Green dye-degrading enzymes. Furthermore, out of 309 bacterial isolates, 42 exhibited antibacterial activity against , 34 against , 47 against ser. Typhimurium and 43 against . Artificially fermented samples exerted higher antibacterial activity compared to fresh BCP, strongly indicating that BB microbiota contribute to BB antibacterial activity. Our findings suggest that BB microbiota is an underexplored source of novel antimicrobial agents and enzymes that could lead to new applications in medicine and the food industry.
PubMed: 38931428
DOI: 10.3390/ph17060761 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Nowadays, lipidomics plays a crucial role in the investigation of novel biomarkers of various diseases. Its implementation into the field of clinical analysis led to the...
Nowadays, lipidomics plays a crucial role in the investigation of novel biomarkers of various diseases. Its implementation into the field of clinical analysis led to the identification of specific lipids and/or significant changes in their plasma levels in patients suffering from cancer, Alzheimer's disease, sepsis, and many other diseases and pathological conditions. Profiling of lipids and determination of their plasma concentrations could also be helpful in the case of drug therapy management, especially in combination with therapeutic drug monitoring (TDM). Here, for the first time, a combined approach based on the TDM of colistin, a last-resort antibiotic, and lipidomic profiling is presented in a case study of a critically ill male patient suffering from -induced pneumonia. Implementation of innovative analytical approaches for TDM (online combination of capillary electrophoresis with tandem mass spectrometry, CZE-MS/MS) and lipidomics (liquid chromatography-tandem mass spectrometry, LC-MS/MS) was demonstrated. The CZE-MS/MS strategy confirmed the chosen colistin drug dosing regimen, leading to stable colistin concentrations in plasma samples. The determined colistin concentrations in plasma samples reached the required minimal inhibitory concentration of 1 μg/mL. The complex lipidomics approach led to monitoring 545 lipids in collected patient plasma samples during and after the therapy. Some changes in specific individual lipids were in good agreement with previous lipidomics studies dealing with sepsis. The presented case study represents a good starting point for identifying particular individual lipids that could correlate with antimicrobial and inflammation therapeutic management.
PubMed: 38931420
DOI: 10.3390/ph17060753