Search Results (226)

Sulfonamide antibiotics threaten ecosystems, yet their phytotoxic mechanisms remain elusive. Here, we demonstrate that sulfonamides inhibit root growth by disrupting the ROS-ethylene signaling axis. Sulfadiazine (SD) strongly inhibits root elongation, an effect strictly dependent on ACS1, as the acs1-1 mutant is completely insensitive. Mechanistically, SD triggers an RBOH-dependent ROS burst that transcriptionally induces ACS1. Since ACS1 forms active heterodimers with ACS2/ACS6, acs2-1 and acs6-1 mutants exhibit partial insensitivity. Furthermore, SD partially depends on the MPK3/6 cascade to post-translationally stabilize ACS2/ACS6, with mpk3 and mpk6 mutants showing partial resistance. Collectively, sulfonamides employ a dual-pronged mechanism: ROS transcriptionally activate ACS1, while MPK3/6 post-translationally stabilizes ACS2/ACS6, driving aberrant ethylene precursor ACC biosynthesis and root growth inhibition. Full article

The ecological risks brought by sulfadiazine (SDZ) residues in the environment have put forward requirements for efficient antibiotic treatment technologies. In this study, biogenic manganese oxides (BMOs) were synthesized using the bacterium Stenotrophomonas maltophilia DT1, and a BMO/syringaldehyde (SYR) system was constructed for SDZ degradation to investigate its performance, mechanism, and potential application. Results showed that the DT1-synthesized BMO contained Mn (II/III/IV) and defect-related oxygen species, which enabled the BMO to participate in SYR activation and SDZ transformation. A total of 99.67% of 10 mg/L SDZ was removed within 3 h under optimized conditions. Humic acid and most environmental ions had no significant interference with the system, except for slight inhibition by Fe³⁺ and Mn²⁺. Three degradation pathways of SDZ were elucidated through the identification of five transformation products and density functional theory calculations. ECOSAR toxicity prediction and growth inhibition of Escherichia coli revealed that the degradation products exhibited significantly reduced toxicity. Furthermore, the BMO exhibited 4.41–17.47 times higher SYR-mediated SDZ transformation efficiency than chemically synthesized manganese oxide (CMO) and showed good performance in reuse tests and real water matrices. This study provides an efficient and eco-friendly green technology for the remediation of SDZ pollution in aquatic environments and provides potential support for the removal of refractory pollutants mediated by BMO. Full article

Background/Objectives: Burn injuries in children represent a significant clinical challenge, as current standard-of-care agents such as silver sulfadiazine (SSD) present limitations, including delayed re-epithelialization. This study aimed to evaluate the therapeutic potential of Castanea sativa (sweet chestnut) flower extract—rich in polyphenols and flavonoids with documented antioxidant, anti-inflammatory, and antimicrobial properties but previously uncharacterized in burn wound healing—applied topically on second-degree burn wounds in a juvenile rat model, comparing its efficacy to SSD and their combination. Methods: Forty five-week-old female Wistar albino juvenile rats were randomly allocated into five groups (n = 8): burn control (Group C), SSD monotherapy (Group BS), vaseline vehicle/sham (Group Sham), 5% chestnut flower extract (Group BCs), and SSD combined with extract (Group BSCs). All topical treatments were applied once daily for 14 days. Healing outcomes were assessed by macroscopic wound closure analysis, systemic organ stress markers (ALT, AST, BUN), oxidative stress indices (MDA, SOD, CAT, GPx, GSH), inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10), and histopathological/immunohistochemical analyses (Ki-67, VEGF). Results: All active treatment groups demonstrated significant reductions in organ damage markers, oxidative stress burden, and pro-inflammatory cytokine levels, alongside enhanced antioxidant enzyme activity, compared to Group C (p < 0.001). Extract-treated groups exhibited more pronounced suppression of oxidative and inflammatory parameters than SSD monotherapy. The combination group (BSCs) achieved optimal wound healing outcomes, including near-complete re-epithelialization, superior collagen organization, and prominent angiogenesis, corroborated by the highest Ki-67 proliferation index and VEGF expression scores (p < 0.001). Conclusions:C. sativa flower extract significantly accelerates burn wound healing via antioxidant and anti-inflammatory mechanisms. When combined with SSD, a synergistic effect is observed that overcomes the re-epithelialization delays associated with SSD monotherapy. These findings support C. sativa flower extract as a promising candidate for further preclinical and clinical investigation in pediatric burn management, supporting the ethnopharmacological relevance of this plant in traditional wound care practices; further safety and efficacy validation is required before clinical translation. Full article

Background/Objectives: Cyclodextrin-based ternary systems are widely used to improve the solubility of poorly soluble drugs. Amino acids such as L-arginine may further increase dissolved drug concentrations and reduce precipitation under physiologically relevant conditions. In many systems, apparent solubility enhancement is influenced simultaneously by drug ionization, inclusion complex formation, multicomponent interactions, and solid–liquid equilibria. This study presents a physicochemical modeling approach for analyzing pH-dependent solubility enhancement and precipitation behavior in drug–cyclodextrin–L-arginine systems. Methods: The model combines acid–base equilibria, binary inclusion complexation, ternary association, and explicit solid-phase partitioning within a unified mass-balance treatment. The approach was applied to representative ternary systems containing repaglinide, sulfadiazine, cefixime, and meloxicam. Results: Quantitative comparison with published phase-solubility data for the repaglinide–HPβCD–L-arginine system confirmed the numerical consistency of the model. The calculated profiles showed that enhanced solubilization and reduced precipitation occur only within specific pH regions determined by coupled equilibrium effects. For cefixime and meloxicam, the calculations were interpreted as predictive applications because directly comparable validation datasets were not available. Outside the favorable pH regions, a substantial fraction of the drug remained in the solid phase. Conclusions: These observations support the importance of pH and multicomponent interactions in controlling formulation performance in cyclodextrin-containing systems. The obtained profiles may support preliminary optimization of formulation pH and excipient composition before experimental screening. Full article

Sulfachloropyridazine (SCP) is a sulfonamide antibiotic widely detected in aquatic environments. Its terminal pyridazine ring contains vicinal pyridinic nitrogen atoms (=N–N=) with strong metal-complexing ability, which may cause distinct interactions with metal-oxide filter media. Here, we systematically investigated the removal of sulfonamide antibiotics by natural manganese sand (NMS), a representative filtration medium in water treatment. NMS exhibited pronounced selectivity toward SCP, while showing negligible removal of sulfadiazine (SD) and sulfamethoxazole (SMX). Under optimal conditions (NMS = 5 g·L⁻¹, pH 3), 99.38% of SCP (5 mg·L⁻¹) was removed within 6 h; the TOC reduction only reached 42.65%, suggesting the partial transformation of SCP. Mechanistic evidence suggests that the vicinal pyridinic N–N motif of SCP provides dual electron-donating sites, enabling inner-sphere Mn–N complexation on NMS. This coordination-driven adsorption is strongly pH-dependent and is inhibited under neutral to alkaline conditions (pH > 5) due to electrostatic repulsion. After selective binding, surface Mn(III)/Mn(IV) species can act as electron acceptors, driving the surface oxidation of SCP. Although NMS induced mild oxidative transformation of SCP, some degradation products still exhibited potential ecotoxicity and therefore require further attention in practical water treatment applications. These findings link terminal functional-group structure to selective abiotic removal on Mn-oxide media and inform targeted control of sulfonamide micropollutants in filtration-based water treatment. Full article

Nanofibrous materials based on chitosan (CS) have attracted considerable attention for advanced wound management due to their excellent biocompatibility and their suitability as drug delivery systems for wound healing applications. Additional surface modification may improve their interaction with the wound environment and influence tissue repair mechanisms. TMC/CS nanofibers were fabricated via electrospinning and subsequently processed into three formulations: unloaded fibers (NCC), norfloxacin-loaded fibers (NCX), and norfloxacin-loaded fibers modified with 2-formylphenylboronic acid (NCXA). The resulting materials were characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and UV–Vis spectroscopy. Their therapeutic performance was evaluated in a standardized deep dermal burn model in Wistar rats, with Vaseline gauze and silver sulfadiazine serving as reference treatments. Wound healing progression was assessed through macroscopic examination, histopathological analysis, immunohistochemical evaluation of TNF-α, IL-1β, IL-17, VEGF, VCAM, and CD163 expression, and systemic IL-8 determination. Physicochemical characterization confirmed homogeneous nanofiber formation, efficient incorporation of norfloxacin, and successful surface modification. All electrospun formulations promoted improved healing outcomes compared with the untreated control group. Among them, the norfloxacin-loaded nanofiber formulation demonstrated the most pronounced wound-healing effect, characterized by faster re-epithelialization, attenuation of inflammatory mediators during later healing stages, and superior tissue architecture restoration. Conversely, the 2-formylphenylboronic acid-modified norfloxacin-loaded fiber formulation maintained a more persistent inflammatory state and exhibited a slower transition into the remodeling phase. Trimethyl chitosan-based nanofibers loaded with norfloxacin show strong potential as multifunctional wound dressing platforms capable of controlled drug release. The findings indicate that formulation composition plays a critical role in regulating inflammation and tissue regeneration, underscoring the need for continued refinement of chitosan-derived nanosystems for burn wound therapy. Full article

Toxoplasmosis remains one of the most common parasitic infections affecting humans, with significant implications for pregnancy and fetal health. Maternal primary infection during gestation can result in transplacental transmission of Toxoplasma gondii, leading to a wide spectrum of congenital disease. The risk of vertical transmission increases with gestational age, whereas disease severity is inversely related—early infections causing severe neurological and ocular damage, and late infections often resulting in subclinical forms. Advances in serological testing, including IgG avidity assays and molecular diagnostics such as PCR on amniotic fluid, have improved early detection and management. Prenatal treatment with spiramycin or pyrimethamine–sulfadiazine–folinic acid combinations has been associated with reduced transmission and less severe fetal disease in several studies, although the magnitude of benefit remains debated. Long-term follow-up is essential, as late-onset manifestations, particularly chorioretinitis and neurodevelopmental impairment, are common. This narrative review was based on a comprehensive literature search of major medical databases and summarizes current knowledge on the epidemiology, pathophysiology, diagnosis, treatment, and outcomes of toxoplasmosis in pregnancy. Particular emphasis is placed on high-prevalence countries, where greater parasite genetic diversity, distinct epidemiological patterns, and a higher burden of congenital disease pose unique clinical and public health challenges. Despite progress in understanding parasite biology, pathogenesis, and treatment efficacy, congenital toxoplasmosis continues to be underdiagnosed and underreported, especially in low-resource settings. Ongoing challenges include optimizing screening strategies, ensuring access to standardized therapies, and strengthening surveillance systems. Full article

The Yellow River Delta (YRD), a crucial ecotone, is becoming increasingly polluted by antibiotics, posing serious threats to aquatic ecosystems and human health. In this study, comprehensive investigations were conducted to explore the regional distribution, environmental risks, and source apportionment of antibiotics, with the aim of facilitating precise management and control of antibiotic pollution. The results show that the surge in runoff during the water–sediment regulation period (June and August) of the Yellow River drove a sharp rise in antibiotic concentrations in the surface water, peaking at 135.0 ng/L, whereas antibiotics were rarely detected in the sediments after multiple rounds of intense hydraulic scouring (0.2~12.6 ng/g in October). Furthermore, seven antibiotics (sulfadiazine, sulfamethoxazole, flumequine, ofloxacin, tetracycline, doxycycline, and lincomycin) in surface water and six antibiotics (norfloxacin, enrofloxacin, ofloxacin, doxycycline, oxytetracycline, and florfenicol) in sediments were identified as representative compounds according to the antibiotic pollution profiles. Environmental risk assessment coupled with spatial autocorrelation analysis revealed that sulfamethoxazole generally posed medium to high risk (0.12~1.27) in surface water. Sediments posed more serious ecological risks, with universally high risk levels (ranging from 1.11 to 280.00). More importantly, in both surface water and sediment, four core antibiotic sources—namely, human sewage, livestock farming, agricultural and aquaculture inputs, and hydrodynamic-driven resuspension processes—were consistently identified through the Positive Matrix Factorization model and Kriging interpolation. These findings provide crucial insights for establishing targeted antibiotic pollution control strategies in the YRD and advance the understanding of antibiotic fate in sediment-laden rivers. Full article

Background and Objectives: Central venous catheters (CVCs) are widely used in intensive care units (ICUs) but are associated with catheter-related bloodstream infections (CRBSIs), which increase morbidity, mortality, and healthcare costs. Antimicrobial-impregnated catheters, including chlorhexidine–silver sulfadiazine (CSS)-coated CVCs, have been proposed to reduce this risk. This study evaluated the effectiveness of CSS-coated CVCs in preventing CRBSIs in ICU patients. Materials and Methods: A retrospective multicenter study was conducted in two ICUs in Naples, Italy. Patients admitted between October and December 2020 who received standard uncoated CVCs (Group A) were compared with patients admitted between October and December 2021 who received CSS-coated CVCs (Group B). Inclusion criteria were age 18–89 years, ICU admission with CVC placement, and negative blood cultures at admission. The primary outcome was the incidence of CRBSI, defined according to microbiological criteria consistent with current guidelines. The secondary outcome was the number of catheter removals due to confirmed CRBSI. Results: A total of 320 patients were included (170 in Group A and 150 in Group B). Baseline demographic characteristics and ICU admission diagnoses were comparable between groups. Microbiologically confirmed CRBSI incidence was significantly lower in Group B than in Group A (6.4% vs. 31.7%, p < 0.0001), corresponding to infection rates of 1.48 vs. 6.95 per 1000 catheter-days, respectively (p < 0.0001). Patients in Group B also required fewer catheter removals due to CRBSI (mean 1.6 vs. 3.2 per patient, p < 0.0001). Logistic regression confirmed a significantly lower risk of CRBSI with CSS-coated CVCs (OR 0.15; 95% CI 0.06–0.32). Conclusions: CSS-coated CVCs were associated with a significant reduction in CRBSI incidence and catheter replacement rates in ICU patients. However, given the retrospective design, univariable analysis, and highly unequal pandemic-related systemic stressors between the two periods, these findings demonstrate a clinical association rather than direct causation, and should be interpreted with caution due to potential residual confounding. Full article

Toxoplasma gondii is an obligate intracellular parasite that infects virtually all warm-blooded animals, progressing through acute and chronic stages. The Akt/mTOR signaling axis plays critical roles in cell survival, proliferation, and metabolism, making it a key target for intracellular pathogens. This study investigated how T. gondii infection modulates this pathway during both infections. Outbred CD-1 mice were infected intraperitoneally with the virulent GT1 strain of T. gondii. Mice for acute studies were sacrificed five days post-infection, while those for chronic studies were treated with sulfadiazine and sacrificed five months post-infection. Phosphoprotein expression of eight Akt/mTOR pathway components was measured in liver tissues using a multiplexed bead-based immunoassay. Acute T. gondii infection caused broad suppression of Akt/mTOR signaling, with 6 of 8 markers significantly downregulated, including pS6RP^Ser235/236, pAKT^S473, pBAD^Ser136, pIRS1^S636/639, pPTEN^Ser380, and pGSK-3α/β^Ser21/9. In contrast, chronic infection related to cyst burden selectively activates specific nodes of the pathway, including pBAD^Ser136, pmTOR^Ser2448, and pGSK-3α/β^Ser21/9. Infection induced strong correlations between inter-components, which reflect coherent and coordinated pathway-level reprogramming rather than random perturbation. These findings show that acute and chronic T. gondii infections have opposing effects on host Akt/mTOR signaling for their own benefit, which may present new therapeutic targets. Full article

Background: This study investigates a novel alginate–gelatin hydrogel incorporating polyphenol-rich grape skin extract as a multifunctional therapeutic system for diabetic wound healing. The extract was obtained by ultrasound-assisted extraction and formulated into a biopolymer hydrogel designed to combine optimal moisture retention with the controlled release of bioactive compounds. Methods: A streptozotocin-induced diabetic rat model was used to evaluate wound contraction, collagen deposition, oxidative stress parameters, and systemic inflammatory markers over a 15-day period. Animals were assigned to four groups: untreated control, silver sulfadiazine (SSD), empty hydrogel (EH), and extract-loaded hydrogel (LH). Results: The LH formulation demonstrated superior wound closure, reaching 97.1% by day 15, significantly outperforming SSD and other groups. Hydroxyproline levels were markedly elevated in LH-treated tissues, indicating enhanced collagen synthesis and extracellular matrix formation. Redox analyses revealed substantial reductions in TBARS and significant increases in SOD, CAT, and GSH, confirming the strong antioxidative activity of the incorporated extract. Moreover, LH treatment produced pronounced decreases in IL-6 and TNF-α, restoring inflammatory balance and facilitating timely progression from the inflammatory to proliferative phase. Conclusions: These effects are attributed to the synergistic actions of grape skin polyphenols which exerted broad biochemical and structural benefits essential for diabetic wound repair. Overall, this sustainable, bioactive hydrogel represents a promising alternative for advanced wound care. Full article

To address the limited selectivity of conventional membrane materials toward sulfonamide antibiotics, this study employed a DFT calculation approach to optimize the design of a molecularly imprinted system for sulfadiazine (SDZ). A hierarchical set of template molecules—aniline (ANL), sulfanilamide (SNM), and SDZ—was introduced to systematically elucidate structure-dependent template–monomer matching mechanisms in sulfonamide imprinting systems. Through rational screening, trifluoroethyl methacrylate (TFEMAA) was identified as the optimal functional monomer, with an optimal imprinting molar ratio of 1:4 (SDZ to TFEMAA). Guided by the simulation results, SDZ molecularly imprinted polymers (MIPs) were synthesized via precipitation polymerization and systematically characterized for their morphology and recognition properties. The MIPs exhibited a well-defined spherical morphology with abundant imprinted cavities, achieving adsorption equilibrium within 1.5 h. The adsorption kinetics followed a pseudo-second-order model, indicating a chemisorption-dominated process. Scatchard analysis revealed the presence of both high- and low-affinity binding sites in the MIPs. Selectivity experiments, quantified by distribution coefficients (K_d) and selectivity coefficients (k), demonstrated a significantly higher adsorption capacity for SDZ than for structural analogs and non-analogs. In real water samples, the MIPs outperformed conventional HLB sorbents and showed strong anti-interference capability (RSD < 3%). This work provides a material foundation for developing highly selective SDZ-imprinted membranes and advances the application of molecular imprinting technology in membrane separation systems. Full article

Cerebral toxoplasmosis is a rare but potentially fatal opportunistic infection in renal transplant recipients receiving long-term immunosuppressive therapy. It may result from donor-derived transmission or reactivation of latent infection. We report the case of a 70-year-old female who underwent kidney transplantation from a deceased donor in 2004 for end-stage renal disease due to glomerulonephritis. She was maintained on cyclosporine, mycophenolate mofetil, and prednisone. In September 2024, she presented with headache, mood changes, and right-sided hemiparesis. Brain multislice computed tomography revealed a large temporoparietal lesion initially suspected to be glioblastoma. Craniotomy and histopathological analysis demonstrated encysted Toxoplasma gondii bradyzoites within gliotic tissue. Polymerase chain reaction testing confirmed the presence of T. gondii DNA, while human immunodeficiency virus testing was negative. The patient reported frequent contact with domestic cats. Treatment with pyrimethamine, sulfadiazine, and leucovorin, alongside adjustment of immunosuppressive therapy, led to marked neurological improvement and radiological regression of the lesion. However, nine months later, she succumbed to multidrug-resistant urosepsis. This case highlights the diagnostic challenges of cerebral toxoplasmosis in transplant recipients, as radiological findings are often nonspecific and can mimic neoplastic or lymphoproliferative lesions. Polymerase chain reaction and histopathological analysis remain essential for definitive diagnosis. Awareness of this rare complication is critical for early recognition and prompt initiation of anti-toxoplasma therapy, which can significantly improve outcomes. Although cerebral toxoplasmosis is uncommon after kidney transplantation, it should be considered in immunosuppressed patients presenting with neurological symptoms. Early detection and targeted therapy are key to reducing morbidity and mortality in this population. Full article

The objective of this study was to evaluate relationships between antimicrobial use (AMU) and antimicrobial resistance (AMR) in isolates from farmed Atlantic salmon that could represent finfish pathogens in the British Columbia (BC) aquaculture industry using historical surveillance data. Antimicrobial susceptibility data were obtained for 1040 bacterial isolates from farmed Atlantic salmon submissions to the BC Animal Health Centre for 2007–2018. Antimicrobial use data were provided by the BC Ministry of Agriculture and Food from feed mill prescriptions for BC farmed Atlantic salmon for 2007–2018. Multivariable logistic regression models for all bacterial isolates with a random intercept for species were developed to determine associations with outcomes of resistance to trimethoprim-sulfadiazine (SXT), oxytetracycline (OXY), and florfenicol (FLOR). Resistance to SXT, FLOR, and/or OXY were all significantly associated with each resistance outcome in their respective models. Only the SXT resistance model was significantly associated with AMU, specifically potentiated sulfonamide use, but use was not significantly associated with AMR for any other resistance outcome. The results of this study contribute to the rapidly growing and increasingly pertinent body of literature on AMU and AMR in the unique marine aquaculture environment. Future research at the farm level linking pen-specific AMU to AMR outcomes will provide more understanding of selection pressure for AMR at the local level and provide more guidance for antimicrobial stewardship in finfish aquaculture. Full article

Devastating or nearly invariably fatal infections caused by free-living amoebae (FLA), including Acanthamoeba keratitis (AK), granulomatous amoebic encephalitis (GAE), and primary amoebic meningoencephalitis (PAM), remain a significant public health concern, driven by increasing case numbers, geographic expansion, and the lack of approved, effective, and safe treatments. Despite decades of research, no new drugs have been successfully approved, highlighting the severe limitations of de novo drug development for these infections, particularly for GAE and PAM, largely due to the challenges of conducting clinical trials for these rare and rapidly lethal diseases. In this context, drug repurposing represents a cost-effective and promising strategy to accelerate therapeutic advances and overcome key bottlenecks of conventional drug development. Accordingly, we conducted a systematic review of in vitro studies and animal models of AK, GAE, and PAM reported in indexed databases to identify promising drug repurposing candidates against FLA infections. After screening 23,624 records, 112 studies were included in the analysis. Overall, 2726 drugs and drug combinations, spanning 865 pharmacological classes and approved for 565 therapeutic indications, were assessed for their repurposing potential. Among these, 166 compounds showed substantial trophocidal activity (≥IC₅₀) at potentially translatable concentrations (≤10 µM), including six with additional cysticidal activity. In vitro, four compounds were active against Balamuthia mandrillaris, 44 against Acanthamoeba spp. (three cysticidal), and 115 against Naegleria spp. (three cysticidal). In in vivo studies, sulfadiazine and rifampicin were effective as preventive or early monotherapies for GAE. For AK, the combination of polyhexamethylene biguanide, neomycin, and atropine, as well as voriconazole and nitazoxanide monotherapies, showed the greatest promise. In PAM, azithromycin alone or in combination with amphotericin B emerged as the most promising therapeutic options. Further studies are required to advance the clinical translatability of these findings. To the best of our knowledge, this work provides the first comprehensive and integrated synthesis of repurposable drug candidates against FLA infections. Full article