Search Results (30)

Environmental contamination with fluorinated compounds has increased markedly due to their widespread use in industry, medicine, and agriculture. Fluoride ions and fluoroquinolone antibiotics may enter soils through fertilizers, wastewater, and manure application, where they can interact with plant-associated microbial communities. In the present study, we investigated the effects of inorganic fluoride (applied as sodium fluoride, NaF) and the fluoroquinolone antibiotic pefloxacin on the growth and microbiome composition of Eruca sativa L. Plants were cultivated under controlled conditions and exposed for four weeks to NaF or pefloxacin at equimolar concentrations of 10 and 20 µM/kg soil. Morphological parameters, including biomass accumulation, root length, leaf dimensions, and leaf area, were not significantly affected by either treatment. Nevertheless, increased variability of growth traits was observed, particularly in plants exposed to NaF. High-throughput sequencing of the 16S rRNA gene revealed pronounced, treatment-specific alterations in both rhizosphere and phyllosphere bacterial communities. The rhizosphere microbiome was relatively stable at higher taxonomic levels but exhibited selective enrichment of Actinomycetota, including the class Thermoleophilia, under NaF exposure. In contrast, the phyllosphere microbiome showed strong sensitivity to fluoride, with a marked increase in Betaproteobacteria, dominated by Burkholderiales. Changes induced by pefloxacin were weaker and more diffuse. Our results demonstrate that plant-associated microbiomes respond to fluorinated compounds at concentrations that do not induce visible plant stress. The phyllosphere microbiome, in particular, represents a sensitive indicator of fluoride exposure and may serve as an early-warning system for environmental contamination. Full article

Fluoroquinolones (FQs) are a kind of antibiotics, which are widely used in animal husbandry and aquaculture. However, the abuse of FQs can result in residues in foodstuffs of animal origin. Therefore, it is essential to establish a sensitive and accurate detection method for determination of FQs in food samples. An effective sample pretreatment method is a crucial procedure for enrichment of trace target compounds from complex matrix before HPLC analysis. As an emerging kind of sample pretreatment methods, magnetic solid-phase extraction (MSPE) has attracted much interest due to its characteristics including low cost, simplicity, and rapidity. In this study, a novel fluorinated magnetic covalent organic framework (Fe₃O₄@PDA@COF) was fabricated, which was used as an adsorbent in MSPE as well as coupled with HPLC to determine FQs in food samples. Under optimal conditions, the developed Fe₃O₄@PDA@COF-MSPE-HPLC-UV method possessed a wide linear range (1–250 µg·kg⁻¹) and low limits of detection (0.5–0.7 µg·kg⁻¹) with good linearity (R² ≥ 0.9938). Additionally, the method has been used to adsorb FQs from chicken samples. The recoveries of target FQs in spiked samples were 84.2–106.7% with relative standard deviations (RSDs) below 7.8%. These results demonstrated that the established method provides an efficient and sensitive solution for monitoring FQ residues in foodstuffs. Full article

Titanium-based implants are widely used in orthopedic and trauma surgery; however, postoperative infections remain a major cause of implant failure due to early bacterial adhesion. Localized antibiotic delivery from surface coatings offers a promising strategy to prevent initial colonization during the critical postoperative period. In this study, a self-organized TiO₂ nanotubular oxide layer was fabricated on Ti-407 by electrochemical anodization in a glycerol/NH₄F electrolyte at 40–60 V. SEM revealed vertically aligned single-walled nanotubes with diameters and lengths of ~80 nm and ~10 µm respectively. XPS analysis verified TiO₂ formation with Al–O, V–O, and fluorine incorporation. Ceftriaxone was successfully loaded into the nanotubular structure, as identified by FT-IR. UV–Vis measurements showed a biphasic release profile consisting of an initial burst followed by sustained release determined by nanotube geometry. In vitro antibacterial activity was evaluated against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli using optical density, CFU quantification, and an agar diffusion assay. Unloaded surfaces showed no inhibition, whereas ceftriaxone-loaded nanotubes significantly reduced bacterial growth up to ~6% and generated clear inhibition zones. These findings demonstrate, for the first time, that TiO₂ nanotubular coatings derived from Ti-407 support drug loading and demonstrate effective in vitro antibacterial activity, highlighting their potential for infection-resistant orthopedic implants. Full article

Droplet microarrays are increasingly used for miniaturized, high-throughput biochemical assays, yet their fabrication commonly relies on complex lithographic processes, custom masks, or specialized coatings. Here we present a simple method for generating hydrophilic arrays on hydrophobic plastic substrates by combining ultrasonic atomization with off-the-shelf perforated masks. A fine mist of poly(vinyl alcohol) (PVA) solution is directed through commercial diamond sieves onto polypropylene (PP) sheets and polystyrene (PS) sheets, forming hydrophilic spots surrounded by the native hydrophobic background. Static contact angle measurements confirm a strong local contrast in wettability (from 100.85 ± 0.91° on untreated PP to 39.96 ± 0.71° on patterned spots, from 95.68 ± 3.61° on untreated PS to 52.00 ± 0.85° on patterned spots), while Image analysis shows droplet CVs of 6–8% in aqueous dye solutions for 1.2–2.0 mm masks; in complex media (LB), droplet uniformity decreases. By mounting the moving mask on a motorized stage, we generate one-dimensional reagent gradients simply by controlling the moving mask motion during atomization. We further demonstrate biological compatibility by culturing Escherichia coli in LB droplets containing resazurin, and by performing localized antibiotic screening using a moving mask-guided streptomycin gradient. The resulting droplet-wise viability data yield an on-chip dose–response curve with an IC₅₀ of 5.1 µg · mL⁻¹ (95% CI: 4.5–5.6 µg·mL⁻¹), obtained from a single array. Covering droplets with Electronic Fluorinated Fluid maintains volumes within 5% of their initial value over 24 h. Compared with conventional droplet microarray fabrication, the proposed method eliminates custom mask production and cleanroom steps, is compatible with standard plastic labware, and intrinsically supports spatial gradients. These attributes make masked ultrasonic atomization a practical platform for high-throughput microfluidic assays, especially in resource-limited settings. Full article

Background: In ectopic adrenocorticotropic hormone (ACTH) syndrome, locating the responsible lesion is often challenging. Case Presentation: A 68-year-old woman was transferred to Nara Medical University hospital for a detailed investigation of her ACTH-dependent Cushing’s syndrome. Because of hypercortisolism-induced immunosuppression, she subsequently developed severe Nocardia pneumonia and was forced to temporarily depend on noninvasive positive pressure ventilation (NIPPV). Intravenous antifungal agents and antibiotics were administered, resulting in significant symptomatic improvement. Metyrapone was administered to suppress excessive cortisol. Contrast-enhanced magnetic resonance imaging of the pituitary revealed a 4 mm sized poorly enhanced area, and microadenoma was suspected. Although cavernous venous sampling was indispensable prior to trans-spheroidal surgery (TSS), this examination could not be performed because of the presence of deep vein thrombosis. TSS was performed for both diagnostic and therapeutic purposes, but hypercortisolism did not improve. Moreover, immunohistochemical findings of the specimen revealed nonfunctional pituitary tumor. Methods: We re-evaluated the responsible lesion causing ACTH-dependent Cushing’s syndrome. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) revealed weak and abnormal FDG uptake in the right pericardium, but the possibility of nonspecific uptake could not be ruled out. However, gallium-68 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic-acid-D-Phe¹-Tyr³-octreotide (⁶⁸Ga-DOTATOC)-PET demonstrated the same degree of abnormal uptake; therefore, a functional pulmonary tumor was strongly suspected. Results: Video-Assisted Thoracic Surgery (VATS) was performed, and histopathological findings of the specimen revealed a neuroendocrine tumor with positive ACTH staining. After VATS, ACTH and cortisol levels were normalized. Conclusions: Here, we report a case of ACTH-dependent Cushing’s syndrome caused by a lung neuroendocrine tumor, in which ⁶⁸Ga-DOTATOC PET was helpful in detecting the functional tumors. Full article

Fluoroquinolones, one of the most frequently used antibiotics, despite their wide spectrum of beneficial activity, are linked to serious adverse effects such as tendinopathies. Tendon injuries connected to the use of the group of drugs frequently affect the Achilles tendon—an anatomical structure, crucial to the proper mobility of lower limb, that is made of collagen fibers and extracellular matrix (ECM). Fluoroquinolones derive and decrease collagen and proteoglycans synthesis; they also disturb tendon regeneration by downregulating activity of metalloproteinases, enzymes essential for the proper collagen remodeling, especially after injuries. The exact way in which fluoroquinolones affect all these processes is not clearly known. However, some studies present that the chemical properties of fluorine such as electronegativity and ability to chelate di- and trivalent metal ions are one of the possible explanations for the problem. Our review summarizes various concepts of fluoroquinolones’ impact on the Achilles tendon structure, particularly collagen type I. What is more, it emphasizes the risk factors for more frequent Achilles tendon damage and presents the potential preventive strategies associated with the usage of the antioxidants. Full article

Background: Transition metal complexes incorporating fluorinated counter anions represent a significant class of compounds with broad applications in industry, pharmaceuticals, and biomedicine. These fluorinated anions are known to enhance the solubility, stability, and reactivity of the complexes, thereby expanding their functional utility in various chemical and biological contexts. Methods: A set of metal(II) complexes of the general formula [MPy₆][B(C₆F₅)₄]₂ where (Py = pyridine, M = Mn (1), Fe (2), Co (3), Ni (4), Cu (5), Zn (6)) have been synthesized by direct reaction of metal halides and pyridine in the presence of Ag[B(C₆F₅)₄]. The complexes were characterized using different techniques to assure their purity, such as elemental analysis (EA), electron paramagnetic resonance (EPR) spectroscopy, thermogravimetric analysis (TGA), ultraviolet–visible (UV–Vis) spectroscopy, ¹¹B-NMR, ¹H-NMR, and FT-IR spectroscopy. The antimicrobial and antifungal properties against different types of bacteria and fungi were studied for all prepared complexes. Results: The synthesized complexes exhibited broad-spectrum antimicrobial activity, demonstrating variable efficacy compared to the reference antibiotic, oxytetracycline (positive control). Notably, complex 6 displayed exceptional antibacterial activity against Streptococcus pyogenes, with a minimum inhibitory concentration (MIC) of 4 µg/mL, outperforming the control (MIC = 8 µg/mL). Complexes 1, 2, and 4 showed promising activity against Shigella flexneri, Klebsiella pneumoniae, and Streptococcus pyogenes, each with MIC values of 8 µg/mL. Conversely, the lowest activity (MIC = 512 µg/mL) was observed for complexes 3, 5, and 6 against Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, respectively. Regarding antifungal properties, complexes 5 and 6 demonstrated the highest activity against Candida albicans, with MIC values of 8 µg/mL, equivalent to that of the positive control, fluconazole. Density functional theory (DFT) calculations confirmed an overall octahedral coordination geometry for all complexes, with tetragonal distortions identified in complexes 3, 4, and 5. Full article

The synthesis of a new acyclic and cyclic series of D-Ala-AMP analogues was reported. Chemical modifications were introduced on the carbohydrate, the sulfamate linker, and/or the amino-acid N-terminal moiety in order to increase in vivo stability and cell permeability. These new compounds were evaluated in vitro as DltA inhibitors and also in vivo as adjuvant antibiotics to re-sensitize methicillin-resistant Staphylococcus aureus. Indeed, we showed that seven nucleosides containing either a fluorine atom, an azido group, a difluorophosphonylated allylic ether moiety onto the 2′-position, or a sulfamate and a triazole as the sulfamate linker had moderate to excellent IC₅₀ values. Among all these new DltA inhibitors, two molecules functionalized by the fluorinated ether or the sulfamide linker were able to efficiently re-sensitize MRSA to imipenem. Quantification of D-alanyl esters confirmed that these two compounds reduced the level of bacterial cell wall D-alanyl residues by 50% and 80%. Full article

Flavonoids and chalcones, widely recognised for their diverse biological activities, have garnered attention due to their potential therapeutic applications. This review discusses fluorinated flavonoids and chalcones, focusing on their prospective anti-inflammatory, antidiabetic, anticancer, antiosteoporotic, cardioprotective, neuroprotective, hepatoprotective, antimicrobial, and antiparasitic applications. The enhanced biological activities of fluorinated derivatives, particularly the antibacterial, antiviral, and anticancer properties, are attributed to the introduction of fluorine groups, which increase lipophilicity and metabolic stability. Key findings indicate that fluorinated flavonoids and chalcones exhibit synergistic effects with antibiotics, inhibit bacterial efflux pumps, and reveal potent antiviral and anticancer properties. However, challenges such as cytotoxicity and structural optimisation have to be addressed. The synthesis of fluorinated flavonoids and chalcones is discussed, with emphasis on various synthetic methods such as condensation and cyclisation reactions starting from fluorinated precursors, as well as fluorination strategies, including the use of molecular fluorine or fluorinating agents. Fluorinated flavonoids and chalcones represent candidates for therapeutic development and have the potential to overcome drug resistance. However, further studies are necessary to adjust their pharmacological profiles. Full article

Background/Objectives: With growing antimicrobial resistance, the overuse of antibiotics, and stagnation in the discovery of new antibiotics, a novel alternative is required to overcome hard-to-treat infections. Antimicrobial peptides (AMPs) show great potential as a possible alternative to standard chemotherapeutics. Temporins are a group of AMPs that have been under the spotlight in numerous studies. Herein, we report the design and synthesis of Temporin A modified in position 1, where the proteinogenic amino acid Phe is replaced by Tyr or fluorinated Phe. In addition, in other analogues, in position 10, the Ser residue is replaced by Tyr or Thr. The aim of all modifications in the primary structure of the native Temporin A is to study the influence of the changes made on the antibacterial properties, antiproliferative activity, and hydrolytic stability of the newly synthesized molecules. Methods: The Fmoc/OBu^t SPPS strategy was employed for the synthesis of the novel-designed analogues. The antibacterial activity was evaluated with both disk diffusion and broth microdilution methods. The BALB 3T3 NRU test and MTT dye reduction assay were used to determine safety and antiproliferative activity. Results: The investigated analogues have low toxicity and are photosafe. The greatest selectivity was shown by DTTyr10 towards MCF-7 cells. DT4F, containing fluorinated Phe in position 1, was the most effective antibacterial agent among the new compounds. The incorporation of Thr in position 10, in comparison with the natural Ser residue, led to an increase in the antiproliferative effect of the new peptide. Conclusions: The obtained structure–activity relationship data show that the most promising compound in the tested series is FLPLIGRVL-Y-GILNH₂, where the Ser residue in position 10 is replaced by a more hydrophobic OH-containing Tyr residue. The analogue containing fluorinated Phe in position 1, DT4F, has the highest antiproliferative effect against both tested tumor cell lines, combined with good antibacterial properties at the lowest MIC (80 µg/mL), but it is more cyto- and phototoxic than the parent DTA molecule and is not stable at pH 9 for a 24 h period. Full article

Prosthetic valve endocarditis (PVE) has undergone significant changes over the past five decades and is currently affecting an aging population, with an increasing prevalence in patients with transcatheter valve implants. The introduction of transcatheter aortic valve replacement (TAVR) represents a significant advance in the field of interventional cardiology and cardiac surgery. The incidence of IE after TAVR has remained stable, with rates similar to those reported after surgical aortic valve replacement. This is despite significant refinements in the TAVR procedure, with less invasive handling and its extension to younger and healthier patients. TAVR should be considered as a potential treatment option for patients with PVE, despite some differences. In terms of evolutionary advances, there have been notable and significant developments in the fields of microbiology and imaging diagnostics. The 2023 Duke-International Society for Cardiovascular Infectious Diseases diagnostic criteria for infective endocarditis now incorporate significant advances in molecular biology and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography. This has led to a significant enhancement in diagnostic sensitivity for PVE while maintaining the same level of specificity in validation studies. PVE is a deadly disease. A multidisciplinary endocarditis treatment team in a cardiac center is essential to improve outcomes. The availability of novel surgical options allows clinicians to offer an increasing number of patients the opportunity to avoid surgical intervention. Some patients will complete antimicrobial treatment at home. Those with prosthetic valves are eligible for antibiotic prophylaxis before dental procedures. Post-TAVR infective endocarditis (IE) is a subcategory of prosthetic valve endocarditis. This condition presents a particularly complex scenario, characterized by a distinctive clinical and microbiological profile, a high prevalence of IE-related complications, an ambiguous role of cardiac surgery, and a poor prognosis for the majority of patients with TAVR IE. The number of TAVR procedures is set to skyrocket in the coming years, which will undoubtedly lead to a significant rise in the number of people at risk of this life-threatening complication. This review will provide an overview of this rare complication in light of the advent of IE following TAVR. It is crucial to gain a comprehensive understanding of the disease and its associated complications to enhance clinical outcomes. Full article

Prosthetic valve endocarditis (PVE) is the medical term used to describe a focus of infection involving a valvular substitute within the heart. It is a significant concern in the field of cardiology, and the epidemiology of PVE has seen notable developments over the last five decades. The disease currently affects an older demographic and is becoming increasingly prevalent in patients with transcatheter-implanted valves. It is imperative that we urgently address the significant challenges posed by PVE. It is a disease that has a wide range of potential aetiologies, clinical presentations, and courses. In developed countries, Staphylococcus aureus is now the predominant causative organism, resulting in an aggressive form of disease that frequently afflicts vulnerable or elderly populations. However, it is clear that Enterococcus species present a significant challenge in the context of PVE following TAVR procedures, given their elevated prevalence. The 2023 Duke/International Society for Cardiovascular Infectious Diseases infective endocarditis diagnostic criteria now include significant developments in microbiological and image-based techniques for diagnostic purposes, specifically the incorporation of fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography. These developments unequivocally enhance the diagnostic sensitivity for PVE, while maintaining the specificity. They do so in accordance with the results of studies conducted specifically for the purpose of validation. The lack of rigorous scientific studies and a shortage of funding and resources for research have led to a significant gap in our understanding. Randomized controlled trials could provide invaluable insight and guidance for clinical practice, but they are missing, which represents a major gap. It is clear that there is an urgent need for more research. PVE is a life-threatening condition that must be handled by a multidisciplinary endocarditis team at a cardiac centre in order to improve outcomes. The emergence of innovative surgical techniques has empowered clinicians to steer more patients away from surgical procedures, despite the presence of clear indications for them. A select group of patients can now complete parenteral or oral antimicrobial treatment at home. Additionally, antibiotic prophylaxis is the best option for individuals with prosthetic valves who are going to have invasive dental procedures. These individuals should be given antibiotics beforehand. Full article

(1) Background: Since the discovery of antibiotics in the first half of the 20th century, humans have abused this privilege, giving rise to antibiotic-resistant pathogens. Recent research has brought to light the use of antimicrobial peptides in polymers, hydrogels, and nanoparticles (NPs) as a newer and safer alternative to traditional antibiotics. (2) Methods: This review article is a synthesis of the scientific works published in the last 15 years, focusing on the synthesis of polymers with proven antimicrobial properties. (3) Results: After a critical review of the literature was made, information and data about the synthesis and antimicrobial activity of antibacterial polymers and NPs functionalized with antibiotics were extracted. Fluorinated surfactants such as the Quaterfluo^® series presented significant antimicrobial effects and could be modulated to contain thioesters to boost this characteristic. Biopolymers like chitosan and starch were also doped with iodine and used as iodophors to deliver iodine atoms directly to pathogens, as well as being antimicrobial on their own. Quaternary phosphonium salts are known for their increased antimicrobial activity compared to ammonium-containing polymers and are more thermally stable. (4) Conclusions: In summary, polymers and polymeric NPs seem like future alternatives to traditional antibiotics. Future research is needed to determine functional doses for clinical use and their toxicity. Full article

One of the main causes of mortality in humans continues to be infectious diseases. Scientists are searching for new alternatives due to the fast increase in resistance of some harmful bacteria to the frontline antibiotics. To effectively treat pathogenic infections, it is crucial to design antibiotics that can prevent the development of pathogenic resistance. For this purpose, a set of 39 quaternary pyridinium and bis-pyridinium salts with different lengths of side alkyl or fluorinated chains, heterocyclic spacers, and counter ions were tested on diverse reference bacterial ATCC (American Type Culture Collection) strains, such as S. aureus and E. coli. Subsequently, 6 out of the 39 pyridinium salts showing relevant MIC (Minimum Inhibitory Concentration) values were tested on clinically isolated, resistant strains of S. aureus, S. epidermids, S. haemolyticus, K. pneumoniae, A. baumannii, and P. aeruginosa. Additional tests have been performed to assess if the minimum concentration detected through MIC assay may limit the growth of biofilms. Full article

Invasive methicillin-resistant Staphylococcus aureus (MRSA) infections are leading causes of morbidity and mortality that are complicated by increasing resistance to conventional antibiotics. Thus, minimizing virulence and enhancing antibiotic efficacy against MRSA is a public health imperative. We originally demonstrated that diflunisal (DIF; [2-hydroxy-5-(2,4-difluorophenyl) benzoic acid]) inhibits S. aureus virulence factor expression. To investigate pharmacophores that are active in this function, we evaluated a library of structural analogues for their efficacy to modulate virulence phenotypes in a panel of clinically relevant S. aureus isolates in vitro. Overall, the positions of the phenyl, hydroxyl, and carboxylic moieties and the presence or type of halogen (F vs. Cl) influenced the efficacy of compounds in suppressing hemolysis, proteolysis, and biofilm virulence phenotypes. Analogues lacking halogens inhibited proteolysis to an extent similar to DIF but were ineffective at reducing hemolysis or biofilm production. In contrast, most analogues lacking the hydroxyl or carboxylic acid groups did not suppress proteolysis but did mitigate hemolysis and biofilm production to an extent similar to DIF. Interestingly, chirality and the substitution of fluorine with chlorine resulted in a differential reduction in virulence phenotypes. Together, this pattern of data suggests virulence-suppressing pharmacophores of DIF and structural analogues integrate halogen, hydroxyl, and carboxylic acid moiety stereochemistry. The anti-virulence effects of DIF were achieved using concentrations that are safe in humans, do not impair platelet antimicrobial functions, do not affect S. aureus growth, and do not alter the efficacy of conventional antibiotics. These results offer proof of concept for using novel anti-virulence strategies as adjuvants to antibiotic therapy to address the challenge of MRSA infection. Full article