Search Results (926)

Background: Enterococcus faecalis is a major cause of complicated urinary tract infections (UTIs), characterized by intrinsic resistance and pronounced biofilm formation. Nitroxoline (NTX), a metal-chelating uroantiseptic, accumulates in urine and exhibits antibiofilm activity. Hydroquinone (HQ), the active urinary metabolite of arbutin-containing herbal preparations, is also excreted into urine and may contribute to antimicrobial activity in situ. This study investigated the antimicrobial and antibiofilm effects of NTX and HQ, individually and in combination, against uropathogenic E. faecalis isolates. Methods: Minimum inhibitory (MIC), bactericidal (MBC), and anti-adhesion (MAC) concentrations were determined using broth microdilution. Interaction was assessed by the checkerboard method and expressed as the fractional inhibitory concentration index (FICI). Biofilm inhibition was quantified by colony-forming unit (CFU) enumeration following exposure to subinhibitory concentrations. Ultrastructural alterations of E. faecalis following exposure to NTX and HQ were examined by transmission electron microscopy (TEM). Results: NTX demonstrated MIC values ranging from 0.002–0.016 mg/mL (MIC50/MIC90: 0.004/0.008 mg/mL), while HQ exhibited MIC values of 0.78–1.56 mg/mL (MIC50/MIC90: 0.78/1.56 mg/mL). Synergistic interactions (FICI ≤ 0.5) were observed in selected isolates, with up to eightfold and sixteenfold reductions in NTX and HQ concentrations, respectively. Additive effects predominated in the remaining isolates without antagonism. The combination achieved 3–5 log₁₀ reductions in adherent bacterial counts compared to untreated controls and up to 4 log₁₀ reductions compared to single-agent exposure. In several strains, complete inhibition of adhesion was observed. TEM analysis revealed marked envelope disruption, cytoplasmic condensation, and structural collapse following combined treatment. Conclusions: Given that both NTX and HQ are active within the urinary environment, their combination may represent a pharmacologically relevant strategy targeting both bacterial growth and early biofilm establishment in enterococcal UTIs. These findings support further in vivo and pharmacokinetic investigations to evaluate the clinical applicability of this combination. Full article

Background/Objectives: Radiolabeled bevacizumab-based immuno-PET tracers enable a non-invasive quantification of VEGF-A expression in gynecologic malignancies. While the previously reported [⁵²Mn]Mn-DOTAGA-bevacizumab demonstrated selective VEGF-A-targeted uptake in a KB-3-1 cervix carcinoma mouse model, further improvements in chelator stability and tumor-to-background contrast remain desirable. The recently developed BPPA chelator exhibits exceptionally high Mn(II) complex stability and favorable radiolabeling characteristics. This study aimed to characterize the in vivo biodistribution of [⁵²Mn]Mn-BPPA-bevacizumab, and to compare the tumor-to-background ratios of [⁵²Mn]Mn-BPPA-bevacizumab with the previously published values of [⁵²Mn]Mn-DOTAGA-bevacizumab in VEGF-A-expressing cervix carcinoma. Methods: Female KB-3-1 tumor-bearing CB17 SCID mice underwent PET/MRI imaging following intravenous administration of [⁵²Mn]Mn-BPPA-bevacizumab. SUV_mean values were measured in various organs and in the subcutaneously injected tumor, and tumor-to-organ ratios were calculated at various time points up to 10 days post-injection. Results: [⁵²Mn]Mn-BPPA-bevacizumab demonstrated sustained tumor uptake, with tumor SUVmean values increasing from approximately 1.0 at 4 h to peak values of approximately 2.4–2.5 at 72 h post-injection. Tumor-to-background ratios increased progressively over time and were significantly higher for [⁵²Mn]Mn-BPPA-bevacizumab compared with previously reported [52Mn]Mn-DOTAGA-bevacizumab, particularly for tumor-to-blood, tumor-to-liver and tumor-to-lung ratios at later imaging time points (p < 0.0001). Conclusions: The novel [⁵²Mn]Mn-BPPA-bevacizumab tracer exhibits satisfactory in vitro and in vivo stability for PET imaging, high VEGF-A-specific tumor uptake, and markedly improved tumor-to-background ratios compared to the previously published DOTAGA-based probe. These results position [⁵²Mn]Mn-BPPA-bevacizumab as a highly promising next-generation immuno-PET agent for imaging VEGF-A-expressing gynecologic malignancies and for guiding anti-angiogenic therapies. Full article

The rapid detection of zinc in different aqueous matrices is very relevant. For example, a Zn²⁺ level above ca. 50 µM affects drinking water quality, while levels below ca. 25 µM in urine are related to higher probability of prostate cancer. Herein, a simple and rapid qualitative colorimetric sensor for the detection of zinc ions in aqueous samples is developed. The sensor exploits the reaction between 1,5-diphenylthiocarbazone and Zn²⁺ to form colored chelates whose color changes with increasing Zn²⁺ concentration. The chelating agent has been immobilized in a dried form on various cellulose- and synthetic-based materials to obtain a sensor that can be used for in situ analysis. The procedure to obtain the colorimetric device is easy and straightforward. Moreover, it requires neither specialized personnel to perform the analysis nor specialized personnel for the interpretation of the analytical results. The analysis requires only 20 µL of sample, and a reliable colorimetric output is obtained within 10 min and is stable up to 30 min. The sensor allows Zn²⁺ visual detection in drinking water and urine without any sample pre-treatment with excellent efficiency and repeatability. Considering the ability to distinguish between Zn²⁺ concentrations equal to 0.5 and 2× the cut-off level, the sensor showed sensitivity and specificity of 100% for fortified tap water analysis and 100% sensitivity and 88.9% specificity for urine samples. The almost-perfect concordance with the reference atomic absorption spectrometer and the 94.1% accuracy demonstrated the sensor’s excellent potential to be applied for selective qualitative Zn²⁺ detection in real-life situations. Full article

Carnosine (or β-alanyl-L-histidine) is an endogenous compound playing very important roles in human organisms as antiglycation and antioxidant agents, and, in addition, helping to mitigate illnesses such as cancer and neurodegenerative diseases. Aiming to explore the chelating ability of carnosine, based on its coordinating possibilities, we started to investigate the metal complexes of essential copper(II), zinc(II), and iron(II) ions coordinated to this dipeptide. Different compounds were isolated in the solid state by adding stoichiometric amounts of metal salts to carnosine at controlled pH or under a controlled atmosphere, with the formation of mono-, bi- and polynuclear species. These complexes were subsequently characterized mainly by spectroscopic techniques (UV–Vis, IR, EPR), in addition to elemental analysis. A binuclear species was isolated with copper(II) and had its structure determined by X-ray diffraction, improving previously reported data in the literature. Two insoluble correlated trinuclear species were isolated with zinc(II) ions, using perchlorate or chloride as counter-ions. In the case of iron, a mononuclear species was verified with Fe(II) ions, obtained under an inert atmosphere. Further, the antioxidant properties of free carnosine and the copper–carnosine complex were verified by their scavenging activity toward the ABTS^•+ radical, using Trolox as a reference, showing significant activity. The carnosine–metal complexes were also tested as potential antineoplastic agents, in comparison to the free ligand, after 24 h of incubation at 37 °C, using malignant HeLa, SKMEL 28 and SKMEL 147, and non-tumor fibroblast cells. Results indicated neglected or poor anti-proliferative properties of these metal complexes, when compared to other similar compounds described in the literature. Full article

Gadolinium nanoparticles (GdNPs) have gained increasing attention as multifunctional metal-based nanoplatforms that extend far beyond their traditional use as magnetic resonance imaging (MRI) contrast agents. Their specific magnetic properties, tunable physicochemical features, and tunable biocompatibilities with biocompatible coatings give them great potential as drug delivery and theranostic applications. They offer greater stability, lower systemic toxicity, and more surface modification options compared to molecular gadolinium chelates. The functionalized GdNPs not only show excellent properties as drug carriers for their specific indications but also serve as agents in various imaging modalities with superior therapeutic efficacy by means of radio sensitization and magnetically assisted delivery. Note too that GdNP-based formulations have demonstrated synergistic activity when administered with chemotherapeutic agents such as doxorubicin. GdNPs have demonstrated promising preclinical outcomes, and their clinical translation remains restricted due to a number of scale-up constraints, long-term safety challenges, pharmacokinetics, and regulatory problems. This review provides information on the use of GdNPs, their key physicochemical and magnetic properties, ligand engineering for targeted delivery, and biological mechanisms of their theranostic performance. Full article

Magnetic resonance imaging (MRI) is one of the most powerful non-invasive methods for cancer diagnostics. To enhance image contrast and, therefore, diagnostic accuracy, contrast agents (CAs) are widely used in clinics. For decades, the clinical standard has been metal-based CAs, primarily gadolinium- and manganese-based chelates, or iron oxide nanoparticles. However, metal-based CAs possess sub-effects, toxicity, and associated adverse health effects, such as nephrogenic systemic fibrosis. As an alternative, metal-free organic radical CAs (ORCAs), based on nitroxides, have been developed. ORCAs are widely used as primary ¹H-MRI agents and offer many advantages, including high biocompatibility, biodegradability, and easy functionalization. Attachment of nitroxides to natural or synthetic polymers enables the development of constructs with prolonged systemic circulation time and tumor-targeted delivery. Furthermore, MR-signal amplification can be achieved through physical hyperpolarization techniques, such as dynamic nuclear polarization (DNP) and Overhauser-enhanced MRI (OMRI), in which nitroxide radicals serve as hyperpolarizing agents, yielding signal enhancements. This review summarizes low-molecular-weight nitroxides, polymeric, and biomacromolecular platforms for ¹H-MRI, focusing on physicochemical properties, preclinical evidence in tumor imaging, and current limitations. One section highlights the use of nitroxides as hyperpolarizing agents for tumor metabolism analysis or OMRI. The review addresses ongoing challenges and outlines future perspectives for the clinical translation of ORCAs in cancer diagnostics. Full article

Gut disorders are largely caused by iron-induced microbial dysbiosis. Excess iron disrupts barrier integrity by inducing oxidative stress, leading to impaired cellular processes. The determination of therapeutic compounds that can reduce iron-induced damage and maintain gut cellular integrity is still a top objective. Dimercaprol (DP) represents a novel iron-chelating strategy for the treatment of iron-induced gut disorders. A chronic iron-overload model was established in mice via intragastric gavage of ferric citrate (FC) (286 mg/kg BW) for 16 weeks. Similarly, IPEC-J2 cells were exposed to FC (50 µmol/L) for 24 h. DP was used as a mechanistic probe to elucidate the pathways involved in iron-induced toxicity. Cells were transfected with or without NRF2 siRNA and exposed to DP post-FC. Colonic contents were assessed via metagenomics and metabolomics. Both in vivo and in vitro experiments were analyzed through a multifaceted analysis, Western blot, RT-qPCR, ELISA, transmission electron microscopy and immunofluorescence assays. Thiols in DP protect gut cells from damage by boosting their natural antioxidant defenses via the NRF2/HO-1 pathway. The DP mechanism of action is multifaceted, including enhancement of barrier integrity, protecting mitochondrial structure and function, suppression of inflammation and endoplasmic reticulum (ER) stress and restoration of gut microbial and metabolic homeostasis. These protective effects are mainly caused by the activation of the NRF2/HO-1 pathway, which makes DP a potential therapeutic agent for disorders caused by chronic gut injury induced by FC. DP provides strong protection against iron-induced gut damage by restoring organelle crosstalk, redox homeostasis and microbial–metabolic balance through NRF2/HO-1 signaling. Full article

In recent years, screen pipe scaling and blockage have occurred in dozens of wells in the Fuling Shale Gas Field, seriously affecting the normal production of gas wells. Investigations show that similar problems exist in the Weirong Shale Gas Field of Sinopec Southwest Branch, and the Changning and Weiyuan Shale Gas Fields of PetroChina. Although well production has been restored through pipe inspection operations, key issues specific to shale gas wells remain unresolved, including the scaling mechanism under gas–liquid two-phase flow regimes unique to horizontal shale gas wells, the scale deposition law at screen pipes caused by complex flow direction changes, and the targeted prevention technologies for high-hardness BaSO₄ scale in high-salinity produced water. By jointly conducting research on the scaling mechanism and prevention technology of shale gas wellbores with Southwest Petroleum University, the Fuling Shale Gas Field has identified the reasons why the amount of BaSO₄ scaling increases with the decrease in pressure and temperature, while it increases with the increase in gas–water ratio. It has clarified the influencing characteristics of factors such as pressure, temperature, gas–water ratio and pipe wall roughness. The amount of scaling on the tubing wall of shale gas wells in this area is very small, and blockage mainly occurs at and near the screen pipe. Due to the complex flow direction change in gas and water in the screen pipe, the precipitated tiny scale particles separate, settle and accumulate, forming variable-diameter steps that continue to grow. Two agents have been developed: the LPPAS scale inhibitor and the barium-strontium-sulfate-chelating plug-removing agent, with a scale inhibition rate as high as over 90% and a scale dissolution rate over 70%, respectively, laying a foundation for the efficient and stable production of shale gas wells. Full article

Sustainable management of vineyard residues through biochar production requires balancing carbon stability with agronomically relevant nutrient functionality. Pyrolysis temperature controls this trade-off by affecting carbon condensation and micronutrient availability. This study aimed to determine how pyrolysis temperatures (300 and 600 °C) govern this trade-off in vineyard-trimming biochars. The motivation focuses on optimizing carbon storage while maintaining micronutrient availability. Biochars were produced by slow pyrolysis at 300 and 600 °C for 1 h and characterized using proximate and elemental analyses, total macro- and micronutrient determination, and DTPA extraction to evaluate potentially bioavailable trace elements. The results showed that increasing temperature from 300 to 600 °C reduced yield (45.15 to 32.30%) and volatile matter (40.33 to 16.50%), while increasing fixed carbon from 55.37 to 77.33% and total carbon from 66.49 to 77.89%. Atomic ratios (H/C: 0.67 to 0.31; O/C: 0.32 to 0.18) confirmed enhanced carbon condensation at 600 °C. Regarding nutrients, although total Mn, Fe, Cu, and Zn concentrations declined at higher temperatures, their potentially bioavailable fractions (operationally defined as extractable with the chelating agent DTPA showed element-specific redistribution; Fe, Cu, and Zn extractability increased, while Mn decreased. These findings reveal a temperature-driven trade-off between carbon sequestration and micronutrient release. Full article

Background/Objectives: Natural polysaccharides have many bio-pharmacological effects, which make them compounds with potential in healthcare. Limnospira platensis (Spirulina), a well-known blue–green cyanobacterium with relevance in the market of nutraceuticals, produces polysaccharides with recognized antioxidant and anti-inflammatory activities. Noteworthy, the growth of the cyanobacterium biomass may be obtained in a more sustainable manner under mixotrophic conditions. In the present study, we compared the antioxidant and anti-inflammatory effects of polysaccharide-enriched extracts from the cyanobacterium cultured under autotrophism (Auto−P extract) or mixotrophism (Mixo−P extract); this latter was realized using medium added with brewery wastewater (BWW). Methods and Results: Non-cellular investigation showed a better antioxidant profile for Mixo−P extract in the OH radical scavenging assay and a similar activity between the extracts in ABTS and ferrous chelation assays. The antioxidant protective activity of L. platensis extracts investigated on HaCat cells in the range of 0.3–10 μg/mL (not cytotoxic concentrations), against hydrogen peroxide (H₂O₂, 600 μM)-induced damage, revealed a similar activity by the two extracts. When tested against the inflammatory stimuli with lipopolysaccharide (LPS, 10 μg/mL) or tumor necrosis factor-α (TNF-α, 10 ng/mL), both Auto−P and Mixo−P showed an ability to prevent the effects of the inflammatory agents on cell viability and on interleukin-1β (IL-1β) and interleukin-6 (IL-6) release, with a slightly greater potency by Mixo−P extract. Conclusions: In conclusion, our data suggest the possible use of L. platensis polysaccharide-enriched extracts in biological-made pharmaceuticals for skin disorders or in cosmeceuticals. In addition, this study demonstrates that mixotrophic cultivation of L. platensis may be an alternative and sustainable way for biotechnological applications of the cyanobacterium biomass. Full article

Dysregulation of iron and copper homeostasis is a pivotal driver of regulated cell death through two distinct yet interconnected modalities: ferroptosis and cuproptosis. This comprehensive review evaluates the therapeutic modulation of these metal-driven pathways within a dual paradigm: their deployment as a cytotoxic weapon in oncology and their inhibition for neuroprotection. We synthesize evidence ranging from small-molecule synergy to advanced nanomedicine, examining how the interplay between iron and copper governs cellular fate in resistant malignancies and neurodegenerative diseases such as Parkinson’s disease and Multiple Sclerosis. In oncology, bimetallic nanoplatforms and CRISPR-Cas9 nano-ionophores exploit “iron addiction” and metabolic vulnerabilities to induce fatal lipid peroxidation and FDX1-mediated proteotoxic stress, often by circumventing efflux transporters like ATP7A/B. Conversely, neuroprotective strategies focus on site-specific chelation, utilizing brain-penetrant molecules like SK4 (targeting the LAT1 transporter) and radical trapping antioxidants like Cu^II(atsm). Importantly, we elucidate the “iron trap” mechanism, where copper deficiency inactivates multicopper ferroxidases—including ceruloplasmin and hephaestin—thereby triggering iron-dependent ferroptosis. Our analysis reveals a self-amplifying cycle of oxidative damage driven by metal-induced ATP depletion and glutathione exhaustion. By delineating the molecular machinery of iron and copper metabolism, this article provides a roadmap for leveraging regulated cell death to overcome apoptosis resistance in cancer and preserve neural integrity in chronic degeneration. Full article

Yersinia pestis and Francisella tularensis are Tier-1 pathogens with high interest for biodefense and public health. Evaluating the antibacterial activity of repurposed drugs against these high-priority pathogens is a key element in the ongoing effort to develop diversified antimicrobial strategies. Drug repurposing offers a cost-effective and time-efficient approach to address antibiotic resistance by identifying new applications for existing therapeutics. In this study, we demonstrate in vitro antibacterial effect of the antifungal agent ciclopirox and offer this drug as a potential antibacterial treatment. Ciclopirox in vitro activity was previously reported against various Gram-negative bacteria, including resistant strains, primarily through iron chelation that disrupts key metabolic pathways and virulence mechanisms. Additionally, it exhibits antibiofilm activity and can potentiate the efficacy of certain antibiotics. Our findings reveal that ciclopirox effectively inhibits the in vitro growth of fully virulent strains of Y. pestis and F. tularensis, as well as avirulent isolates, including avirulent mutants that their wild-type susceptibility was reduced through selection to MIC levels defining them as “nonsusceptible” to ciprofloxacin (Y. pestis Kim53Δ70Δ10 and F. tularensis LVS) and doxycycline (LVS), or resistant to doxycycline (Kim53Δ70Δ10) according to CLSI interpretive criteria. Additionally, prolonged exposure of Y. pestis and F. tularensis to sub-MIC and MIC concentrations of ciclopirox did not lead to an increase in observed MIC during the study period. These results highlight ciclopirox as a potential candidate for treatment alternative, combined with other antibiotic substances or repurposed drugs against these bacterial threats. Full article

Conventional hydrometallurgical processes typically employ inorganic acids as leaching agents; however, these processes are frequently associated with significant environmental pollution and suffer from poor metal selectivity. Oxalic acid, as a green alternative leaching agent, demonstrates considerable application potential owing to its mild acidity, strong reducing capability, and superior complexing properties. This paper presents a systematic review of recent advances in the application of oxalic acid in hydrometallurgy, encompassing the coordination chemistry between oxalic acid and metal ions, its role as a selective leaching agent, and strategies for handling multicomponent oxalate-rich solutions. Furthermore, the industrial prospects of oxalic acid-based leaching technologies are discussed. Research indicates that oxalic acid exhibits high selectivity and efficient leaching performance for critical metals—including vanadium, lithium, cobalt, nickel, and gallium—from both primary ores and solid secondary resources. The underlying leaching mechanism primarily involves the formation of stable chelation complexes between oxalate anions and high charge-density metal ions, or valence state modulation via reduction, enabling selective dissolution and separation of target metals. In multicomponent oxalate systems, where metals predominantly exist as anionic complexes, established enrichment and purification approaches include anion exchange extraction, as well as precipitation techniques based on valence adjustment and double salt crystallization. To advance the industrial implementation of oxalic acid leaching technologies, further in-depth investigation is required into the recycling mechanisms of oxalic acid and the fundamental reaction pathways governing leaching and metal recovery processes. Full article

Copper and zinc nanoparticles have been suggested as potent anticancer agents, particularly against osteosarcoma, a highly aggressive bone cancer with limited treatment options. In order to avoid systemic toxicity, biomolecular carriers able to chelate metal ions and deliver them in a targeted manner to the vicinity of cancer cells need to be developed. Herein, we have used a histidine-containing, cyclic dipeptide as a carrier able to chelate stabilized copper and zinc nanoparticles. The cyclic peptide cyclo-(histidine-phenylalanine) (cHF) self-assembled into amyloid-type fibrils; morphological and structural characterization following metal addition confirmed the formation of cHF−CuNPs and cHF–ZnNPs. These composite nanoparticles demonstrated bacteriostatic activity against Escherichia coli and Staphylococcus aureus at the in vitro level. We evaluated the optimal concentration of cHF–metalNP complexes with limited cytotoxicity to L929 fibroblasts and high cytotoxic effects against MG-63 osteosarcoma cells. Their cytotoxicity was particularly pronounced at pH 6.4, which emulates the tumor microenvironment. The cHF peptide alone did not demonstrate significant antimicrobial or cytotoxic effects to both cell types, suggesting that it can act as a cytocompatible, pH-responsive carrier of metal ions with targeted dual functionality against both microbial infections and osteosarcoma cancer cells. Full article

Iron is an essential micronutrient for nearly all microorganisms, yet its bioavailability is severely limited in most environments. To overcome this restriction, microorganisms produce siderophores, high-affinity iron-chelating molecules that play pivotal roles in microbial iron homeostasis, interspecies competition, and host–pathogen interactions. Despite extensive research, current understanding of siderophore biosynthetic and regulatory diversity remains largely limited to specific models, with comprehensive cross-taxonomic frameworks only beginning to emerge. This review systematically integrates recent advances in the genetic and biochemical foundations of microbial siderophore production, focusing on the two major biosynthetic pathways: nonribosomal peptide synthetase (NRPS)-dependent and NRPS-independent synthetase (NIS). We further elaborate on the diverse transport systems in Gram-negative and Gram-positive bacteria, as well as fungi, alongside the iron-responsive regulators (e.g., Fur) and gene clusters that coordinate iron uptake and utilization. Beyond physiological mechanisms, we discuss how these insights inform emerging applications of siderophores across multiple fields: in medicine, enabling “Trojan horse” antimicrobial strategies; in agriculture, enhancing plant iron uptake and serving as biocontrol agents; in environmental remediation, facilitating heavy-metal detoxification; and in biosensing, acting as selective probes for metals and pathogens. By bridging fundamental mechanisms with practical applications, this review aims to provide an integrative perspective for future exploration of microbial iron homeostasis and its biotechnological potential. Full article