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Heliyon Jun 2024New 3-furan-1-thiophene-based chalcones were synthesized, characterized and pharmacologically evaluated as antibacterial and anticancer agents against two bacterial...
New 3-furan-1-thiophene-based chalcones were synthesized, characterized and pharmacologically evaluated as antibacterial and anticancer agents against two bacterial species; Gram-positive () and Gram-negative (). All tested final compounds were active against the two bacterial species; and . Especially compound AM4 showed large inhibition zone (27.13 and 23.30 mm), respectively. Using the DPPH assay, the new chalcones were evaluated for their free radical scavenging activity and found to reach up to 90 %, accomplished at a test concentration of 200 μg/mL. Furthermore, the chalcone derivatives were investigated against two breast cell lines; MCF-7 (cancerous) and MCF-10A (non-cancerous). Compound AM4 showed potent anticancer activity (IC = 19.354 μg/mL) in comparison to the other tested chalcone derivatives. study was achieved using the PyRx AutoDock Vina software (0.8) to study the interaction types between the new hits and the binding sites of targeted proteins; glucosamine-6-phosphate synthase and tubulin, the target for antibacterial and anticancer drugs, respectively. Based on the molecular docking results the tested chalcones bind to the active pocket of the respective proteins, which support the results. In conclusion, 3-furan-1-thiophene-based chalcones could serve as new hits in the discovery of novel anticancer and/or antibacterial drugs.
PubMed: 38947436
DOI: 10.1016/j.heliyon.2024.e32257 -
Infection and Drug Resistance 2024Contact lenses (CL) have become an immensely popular means of vision correction, offering comfort to millions worldwide. However, the persistent issue of biofilm... (Review)
Review
Contact lenses (CL) have become an immensely popular means of vision correction, offering comfort to millions worldwide. However, the persistent issue of biofilm formation on lenses raises significant problems, leading to various ocular complications and discomfort. The aim of this review is to develop safer and more effective strategies for preventing and managing microbial biofilms on CL, improving the eye health and comfort of wearers. Taking these into consideration, the present study investigates the intricate mechanisms of biofilm formation, by exploring the interplay between microbial adhesion, the production of extracellular polymeric substances, and the properties of the lens material itself. Moreover, it emphasizes the diverse range of microorganisms involved, encompassing bacteria, fungi, and other opportunistic pathogens, elucidating their implications within lenses and other medical device-related infections and inflammatory responses. Going beyond the challenges posed by biofilms on CL, this work explores the advancements in biofilm detection techniques and their clinical relevance. It discusses diagnostic tools like confocal microscopy, genetic assays, and emerging technologies, assessing their capacity to identify and quantify biofilm-related infections. Finally, the paper delves into contemporary strategies and innovative approaches for managing and preventing biofilms development on CL. In Conclusion, this review provides insights for eye care practitioners, lens manufacturers, and microbiology researchers. It highlights the intricate interactions between biofilms and CL, serving as a foundation for the development of effective preventive measures and innovative solutions to enhance CL safety, comfort, and overall ocular health. Research into microbial biofilms on CL is continuously evolving, with several future directions being explored to address challenges and improve eye health outcomes as far as CL wearers are concerned.
PubMed: 38947374
DOI: 10.2147/IDR.S463779 -
Food Chemistry: X Oct 2024Honey is a natural product used since ancient times due to its taste, aroma, and therapeutic properties (antibacterial, antiviral, anti-inflammatory, and antioxidant... (Review)
Review
Honey is a natural product used since ancient times due to its taste, aroma, and therapeutic properties (antibacterial, antiviral, anti-inflammatory, and antioxidant activity). The purpose of this review is to present the species of microorganisms that can survive in honey and the effect they can have on bees and consumers. The techniques for identifying the microorganisms present in honey are also described in this study. Honey contains bacteria, yeasts, molds, and viruses, and some of them may present beneficial properties for humans. The antimicrobial effect of honey is due to its acidity and high viscosity, high sugar concentration, low water content, the presence of hydrogen peroxide and non-peroxidase components, particularly methylglyoxal (MGO), phenolic acids, flavonoids, proteins, peptides, and non-peroxidase glycopeptides. Honey has antibacterial action (it has effectiveness against bacteria, e.g. , , , and etc.), antifungal (effectiveness against spp., spp. spp. spp. and spp.), antiviral (effectiveness against SARS-CoV-2, Herpes simplex virus type 1, Influenza virus A and B, Varicella zoster virus), and antiparasitic action (effectiveness against and ) demonstrated by numerous studies that are comprised and discussed in this review.
PubMed: 38947342
DOI: 10.1016/j.fochx.2024.101524 -
Chemistry & Biodiversity Jun 2024Flavonoids epitomize structural scaffolds in many biologically active synthetic and natural compounds. They showcase a diverse spectrum of biological activities...
Flavonoids epitomize structural scaffolds in many biologically active synthetic and natural compounds. They showcase a diverse spectrum of biological activities including anticancer, antidiabetic, antituberculosis, antimalarial, and antibiofilm activities. The antibiofilm activity of a series of new chalcones and flavonols against clinically significant Pseudomonas aeruginosa PAO1 strain was studied. Antivirulence activities were screened by analysing the effect of compounds on the production of virulence factors like pyocyanin, LasA protease, cell surface hydrophobicity, and rhamnolipid. The best ligands towards the quorum sensing proteins LasR, RhlR, and PqsR were recognised using a molecular docking study. The gene expression in P. aeruginosa after treatment with test compounds was evaluated on quorum sensing genes including rhlA, lasB, and pqsE. The antibiofilm potential of chalcones and flavonols was confirmed by the efficient reduction in the production of virulence factors and downregulation of gene expression.
PubMed: 38946224
DOI: 10.1002/cbdv.202400393 -
Journal of the American Chemical Society Jun 2024bacteria are becoming increasingly resistant against multiple antibiotics. Therefore, the development of vaccines to prevent infections with these bacteria is an urgent...
bacteria are becoming increasingly resistant against multiple antibiotics. Therefore, the development of vaccines to prevent infections with these bacteria is an urgent medical need. While the immunological activity of lipopolysaccharide O-antigens in is well-known, the specific protective epitopes remain unidentified. Herein, we present the first chemical synthesis of highly functionalized aminoglycoside trisaccharide and its acetamido derivative found in the serotype O5 O-antigen. The synthesis of the trisaccharide targets is based on balancing the reactivity of disaccharide acceptors and monosaccharide donors. Glycosylations were analyzed by quantifying the reactivity of the hydroxyl group of the disaccharide acceptor using the orbital-weighted Fukui function and dual descriptor. The stereoselective formation of 1,2--α-fucosylamine linkages was achieved through a combination of remote acyl participation and reagent modulation. The simultaneous S2 substitution of azide groups at C2' and C2″ enabled the efficient synthesis of 1,2--β-linkages for both 2,3-diamino-D-mannuronic acids. Through a strategic orthogonal modification, the five amino groups on target trisaccharide were equipped with a rare acetamidino (Am) and four acetyl (Ac) groups. Glycan microarray analyses of sera from patients infected with indicated that trisaccharides and are key antigenic epitopes of the serotype O5 O-antigen. The acetamidino group is not an essential determinant of antibody binding. The β-D-ManNAc3NAcA residue is a key motif for the antigenicity of serotype O5 O-antigen. These findings serve as a foundation for the development of glycoconjugate vaccines targeting serotype O5.
PubMed: 38946080
DOI: 10.1021/jacs.4c03814 -
International Journal of Biological... Jun 2024The article explores the synthesis of network hydrogels derived from moringa gum (MG) through a grafting reaction with poly (vinylsulfonic acid) and carbopol. These...
The article explores the synthesis of network hydrogels derived from moringa gum (MG) through a grafting reaction with poly (vinylsulfonic acid) and carbopol. These hydrogels are designed for use in drug delivery (DD) and wound hydrogels dressing (HYDR) applications. The copolymers were characterized by FESEM, EDX, AFM, FTIR, C NMR, XRD and DSC. Tetracycline release from hydrogel occurred gradually with a non-Fickian diffusion and was best described by the Hixson-Crowell kinetic model in artificial wound fluid. The HYDR demonstrated compatibility with blood, exhibited antioxidant properties and possessed tensile strength, in addition to their mucoadhesive characteristics. The copolymer dressings absorbed approximately 7 g of simulated fluid. The copolymers exhibited significant antioxidant activity, measuring at 84 % free radicals scavenging, during DPPH assay. These dressings demonstrated permeability to HO and O. The hydrogel alone did not reveal antibacterial activities; however, when combined with antibiotic drug tetracycline, the dressings revealed notable antibacterial activities against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. The observed biomedical properties suggested that these hydrogels could serve as promising materials for drug delivery HYDR applications.
PubMed: 38945716
DOI: 10.1016/j.ijbiomac.2024.133352 -
Journal of Dairy Science Jun 2024Factors contributing to variations in the quality and microbiota of ensiled forages and in bulk tank microbiota in milk from cows fed different forages were...
Factors contributing to variations in the quality and microbiota of ensiled forages and in bulk tank microbiota in milk from cows fed different forages were investigated. Nutritional quality, fermentation parameters and hygiene quality of forage samples and corresponding bulk tank milk samples collected in 3 periods from 18 commercial farms located in northern Sweden were compared. Principal coordinates analysis revealed that the microbiota in forage and bulk milk, analyzed using 16S rRNA gene-based amplicon sequencing, were significantly different. The genera Lactobacillus, Weissella and Leuconostoc dominated in forage samples, whereas Pseudomonas, Staphylococcus and Streptococcus dominated in bulk milk samples. Forage quality and forage-associated microbiota were affected by ensiling method and by use of silage additive. Forages stored in bunker and tower silos (confounded with use of additive) were associated with higher levels of acetic and lactic acid and Lactobacillus. Forage ensiled as bales (confounded with no use of additive) was associated with higher dry matter content, water-soluble carbohydrate content, pH, yeast count and the genera Weissella, Leuconostoc and Enterococcus. For bulk tank milk samples, milking system was identified as the major factor affecting the microbiota and type of forage preservation had little impact. Analysis of common amplicon sequence variants (ASVs) suggested that forage was not the major source of Lactobacillus found in bulk tank milk.
PubMed: 38945265
DOI: 10.3168/jds.2024-24971 -
International Journal of Antimicrobial... Jun 2024Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore...
PURPOSE
Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety.
METHODS
A Model-Based Meta-Analysis (MBMA) of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-day survival rates.
RESULTS
In the study involving 96 articles and 9,716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% CI: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), p=0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), p<0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, p=0.54. The 30-day Overall Survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with β-lactam drugs.
CONCLUSIONS
The dosage of Polymyxin B doesn't significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like Pseudomonas aeruginosa are associated with higher mortality. Combining Polymyxin B with other antibiotics, especially β-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.
PubMed: 38945178
DOI: 10.1016/j.ijantimicag.2024.107262 -
International Journal of Antimicrobial... Jun 2024The proliferation of metallo-beta-lactamase-producing Pseudomonas aeruginosa represents a significant public health threat. P. aeruginosa can undergo significant...
OBJECTIVES
The proliferation of metallo-beta-lactamase-producing Pseudomonas aeruginosa represents a significant public health threat. P. aeruginosa can undergo significant phenotypic changes that can drastically impair antibiotic efficacy. This study's objectives were (1) to quantify the time-course of killing of VIM-2-producing P. aeruginosa in response to aztreonam-based therapies (including avibactam for coverage of AmpC), and (2) to document the capacity of P. aeruginosa to undergo morphological transformations that facilitate persistence.
METHODS
A well-characterized, clinical VIM-2-producing P. aeruginosa was studied in the Hollow Fiber Infection Model (HFIM) over 9 days (7 days of active antibiotic therapy, 2 days treatment withdrawal) at a 10 CFU/mL starting inoculum. HFIM treatment arms included: growth control, aztreonam, ceftazidime/avibactam, aztreonam/ceftazidime/avibactam, polymyxin B, and aztreonam/ceftazidime/avibactam/polymyxin B. In addition, real-time imaging studies were conducted under static conditions to determine the time-course of the reversion of persister cells.
RESULTS
A pronounced discrepancy was observed between OD and bacterial counts obtained from plating methods (hereafter referred to as 'OD-count discrepancy'). For aztreonam monotherapy, observed counts were 0 CFU/mL by 120 h. Despite this, there was a significant OD-count discrepancy as compared to the pre-treatment 0h. Between therapy withdrawal at 168h and 216h, all arms with suppressed counts had re-grown to the system carrying capacity. Real-time imaging of the P. aeruginosa filaments after drug removal showed rapid reversion from a long, filamentous phenotype to many individual rods within 2 h.
CONCLUSION
Managing MBL-producing P. aeruginosa will require a multi-faceted approach, focused on maximizing killing and minimizing proliferation of resistant and persistent subpopulations, which will involve eliminating drug-induced phenotypic transformers.
PubMed: 38945177
DOI: 10.1016/j.ijantimicag.2024.107260 -
Journal of Hazardous Materials Jun 2024Natural attenuation (NA) is of great significance for the remediation of contaminated groundwater, and how to identify NA patterns of toluene in aquifers more quickly...
Natural attenuation (NA) is of great significance for the remediation of contaminated groundwater, and how to identify NA patterns of toluene in aquifers more quickly and effectively poses an urgent challenge. In this study, the NA of toluene in two typical soils was conducted by means of soil column experiment. Based on column experiments, dissolved organic matter (DOM) was rapidly identified using fluorescence spectroscopy, and the relationship between DOM and the NA of toluene was established through structural equation modeling analysis. The adsorption rates of toluene in clay and sandy soil were 39 % and 26 %, respectively. The adsorption capacity and total NA capacity of silty clay were large. The occurrence of fluorescence peaks of protein-like components and specific products indicated the occurrence of biodegradation. Arenimonas, Acidovorax and Brevundimonas were the main degrading bacteria identified in Column A, while Pseudomonas, Azotobacter and Mycobacterium were the main ones identified in Column B. The pH, ORP, and Fe(II) were the most important factors affecting the composition of microbial communities, which in turn affected the NA of toluene. These results provide a new way to quickly identify NA of toluene.
PubMed: 38944985
DOI: 10.1016/j.jhazmat.2024.134952