Search Results (34,231)

The aim of the study was to modify polylactide with zinc oxide nanoparticles (ZnO), raspberry leaf extract (E), and a combined ZnO/extract system (EZnO) in order to prepare novel packaging materials via a solvent-free method, namely cast extrusion. Physicochemical properties: Morphology (GPC, SEM, FTIR), mechanical (tensile tests, puncture), barrier (WVTR, OTR, UV-Vis) and water contact angle for PLA-based films with two thickness ranges were investigated. Additionally, antimicrobial (antibacterial, antifungal and antiviral) tests were performed. GPC results revealed that the presence of the extract counteracted biopolyester degradation during hot melt processing. The best mechanical properties (TS ca. 50 MPa, EB ca. 18%) were obtained for PLA modified with raspberry leaf extract (PLA/E). EZnO addition led to the highest increase in oxygen (with 25%) and water vapor (up to ca. 28%) barrier properties. The material with EZnO addition was also found to be the only one to demonstrate antibacterial effectiveness, although the activity was insignificant. However, the incorporation of EZnO into the biopolymer matrix enhanced its antiviral properties, resulting in the complete inactivation of Φ6 bacteriophage particles used as a surrogate of SARS-CoV-2 virus. Full article

Objective: Given the increasing use of outpatient parenteral antimicrobial therapy (OPAT) and the clinical challenges posed by Pseudomonas aeruginosa infections, this study aimed to evaluate the effectiveness and safety of OPAT for the treatment of P. aeruginosa infections in a real-world cohort. Methods: We conducted a prospective observational study with retrospective analysis including adult patients with P. aeruginosa infections treated within a multidisciplinary OPAT program shared by two tertiary hospitals between November 2012 and December 2024. Clinical characteristics, infection type, antimicrobial therapy, resistance patterns, source control, and clinical outcomes were recorded. Primary outcomes were treatment failure during OPAT and within 30 days after OPAT completion. Secondary outcomes included adverse events and vascular access complications. Bivariate and multivariable logistic regression analyses were performed to identify factors associated with treatment failure. Results: A total of 290 patients were included. The most frequent infections were bronchiectasis exacerbations (39.7%) and complicated urinary tract infections (15.2%). Most patients received monotherapy (72.8%), mainly ceftazidime, while 27.2% received combination therapy with a beta-lactam plus an aminoglycoside. Treatment failure occurred in 7.6% of patients during OPAT and in 15.5% within 30 days after OPAT completion, with an overall clinical success rate of 77%. Male sex and chronic obstructive pulmonary disease (COPD) were independently associated with failure during OPAT. At 30 days, higher Charlson comorbidity index, COPD exacerbation, and endovascular infection were associated with failure, whereas combination therapy was associated with a lower risk of failure. Antimicrobial-related adverse events were rare (3.2%). Conclusions: Our results support OPAT as an effective and safe strategy for managing P. aeruginosa infections in clinically stable patients. Patients with COPD, either as a comorbidity or during an exacerbation, and those with a higher Charlson score may require closer follow-up. Full article

The increasing global demand for sustainable production of high-nutritional-value food and feed has emerged the need of harnessing the agro-industrial residues applying various innovative bioconversion strategies. In this context, the utilization of legume production wastes constitutes an intriguing subject because of their high content in nutritious molecules. The study herein concerns the incorporation of Fava Santorinis (Lathyrus clymenum) pericarps, an agro-industrial byproduct, into Black Soldier Fly (BSF, Hermetia illucens) larvae rearing diets to produce nutritious insect meals. Thus, four dietary treatments of BSF larvae were evaluated consisting of a commercial feed as control diet and three experimental diets incorporating 15%, 30% and 45% inclusion levels of fava bean pericarps. When BSF larvae reached their sixth instar stage, their growth performance and the nutritional content of the produced insect meal were assessed. Best results were obtained for BSF rearing with feed containing 30% and 45% pericarps, establishing the valorization of a large amount of pericarp, achieving a high growth rate and a rich protein content exceeding 30%. On the other hand, the presence of saponines was not determined, although the overall larvae performance indicates a high tolerance to their presence. Finally, the assessment of insect meals lipidic profiles revealed the prevalence of saturated lauric acid, an established potent antimicrobial agent, along with lower amounts of unsaturated Ω-6 linolenic acid and Ω-3 linoleic acid acids. The results herein demonstrate a sustainable strategy for the bioconversion of Fava Santorinis production waste to nutritious animal feed in the context of circular economy. Full article

This study evaluated the effects of light spectral quality on shoot yield and essential oil of Tagetes erecta L. cultivated in controlled growth chambers under three LED lighting treatments with different red, blue, and white wavelength ratios and a constant 16 h photoperiod for up to 101 days. The F2 treatment (5 red:1 blue) produced yields of fresh shoots, early blooming flowers, and oils of 1586 ± 164 g/m², 569.77 ± 76.81 g/m², and 307 ± 31.7 mg/m², respectively. These values were significantly higher (p < 0.05) than those of the F1 treatment (white:red-phosphor), and represented increases of 1.37-, 1.26-, and 1.38-fold, respectively. Gas chromatography identified 30–31 compounds in the oil with three major constituents—(E)-β-ocimene (22.9–28.8%, highest under F3), (E)-myroxide (13.9–20.6%, highest under F1), and piperitone (7.3–9.6%, highest under F3). Essential oils inhibited from four to five of the seven tested microbial strains, with the notable activity against Escherichia coli and Candida albicans recorded in F2 and F1, respectively. These findings confirm that light spectral quality is a critical factor regulating flower, essential oil, and antimicrobial efficacy in T. erecta, demonstrating that optimized LED spectra offer a practical strategy to improve plant yield and phytochemical quality. Full article

The life-threatening disease pertussis, also known as whooping cough, is caused by a complex interplay of several virulence factors produced by the bacterium Bordetella (B.) pertussis. These include the AB-type protein toxin pertussis toxin (PT), the main causative agent of pertussis. After infection with B. pertussis, PT is released and binds to its human target cells, which internalize PT. The enzyme subunit of PT is then taken up into the cytosol, where it catalyzes the ADP-ribosylation of the α-subunit of inhibitory GTP-binding proteins from the Gαi type. This ultimately leads to the development of the characteristic clinical symptoms associated with pertussis. Pertussis is a vaccine-preventable but highly infectious respiratory disease, and especially younger children are prone to develop severe pertussis. Despite the vaccination, over the past few years, increasing case numbers have been reported globally. Moreover, treatment options are strongly limited to antibiotics and symptomatic treatment. Therefore, novel therapies against toxin-mediated diseases are urgently required, while AB-type toxins such as PT are promising pharmacological targets to combat these associated diseases. To identify novel pharmacological inhibitors for AB-type toxins, huge potential lies within the human proteome/peptidome. Endogenous protein or peptide inhibitors for bacterial toxins might have evolved as part of the innate immunity and are awaited to be discovered. The scientific community is committed to identify potential candidates through targeted screening or explorative hypothesis-driven approaches. This review summarizes the recent efforts in the identification and characterization of the human body’s own proteins and peptides that inhibit PT. PT-inhibiting peptides were found by unbiased screening of peptide libraries from human hemofiltrate or hypothesis-driven evaluation, and PT-neutralizing mechanisms were discovered in cell-based approaches. The identification of endogenous peptides and proteins, e.g., defensins and α₁-antitrypsin, as potent inhibitors of PT paves the way towards the development of novel therapeutic options against pertussis. Full article

Background/Objectives: Multidrug-resistant (MDR) Escherichia coli resistant to third-generation cephalosporins are a growing One Health concern, but data on extraintestinal pathogenic E. coli (ExPEC) from wildlife in North Africa remain scarce. We aimed to characterize ESBL/AmpC-producing ExPEC from captive wild mammals in Tunisia and to situate these isolates in a global genomic context. Methods: In 2018, 30 fecal samples from 14 captive wild mammals in a private farm were screened on cefotaxime agar. Four cefotaxime-resistant E. coli isolates were recovered from a llama, lion, hyena, and tiger. Antimicrobial susceptibility testing and Illumina whole-genome sequencing were combined with in silico typing, resistome and virulome profiling, plasmid and mobile element analysis, human pathogenicity prediction and core-genome MLST-based minimum-spanning trees. Results: All isolates were MDR but remained susceptible to carbapenems, colistin and tigecycline. Two ST162/B1 isolates from the llama and tiger carried bla_CMY-2, whereas two ST69/D isolates from the lion and hyena harbored bla_CTX-M-15 and qnrS1. Genomes encoded 61–68 antimicrobial resistance genes and 114–131 virulence-associated genes, together with IncF-, IncI1- and IncY-type plasmids and IS26-rich insertion sequence profiles. Mating-out assays yielded cefotaxime-resistant transconjugants, supporting plasmid transferability of bla_CMY-2 or bla_CTX-M-15. PathogenFinder predicted a ≥0.93 probability of human pathogenicity for all isolates. cgMLST-based trees showed that Tunisian ST69 and ST162 clustered within internationally disseminated lineages containing human, animal and food isolates, rather than forming wildlife-restricted branches. Conclusions: Captive wild mammals in Tunisia can harbor high-risk ExPEC lineages combining ESBL/AmpC production, multidrug resistance and extensive virulence and mobility gene repertoires. These findings highlight captive wildlife as potential reservoirs and sentinels of clinically relevant E. coli and underscore the need for integrated WGS-based One Health surveillance at the human–animal–environment interface in North Africa. Full article

Conventional and emerging extraction methods for recovering phenolic compounds (PCs) from Pinus radiata bark were investigated for their potential use in bio-composites and bio-based biomaterial applications. To optimize the recovery process, a Response Surface Methodology (RSM) based on a Box–Behnken design was used to evaluate the effects of extraction time (20–100 min), temperature (20–80 °C), and water or ethanol-water solvent concentrations with β-cyclodextrin (βCD) or NaOH (0.5–1.5% w/v CD/db). Polyphenolic profiles of the extracts were characterized using Fourier transform infrared spectroscopy (FTIR), LC-LTQ-Orbitrap-MS, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were used to evaluate the thermal stability and degradation behavior of the powdered extracts. Antioxidant capacity (DPPH, FRAP, ABTS) and antibacterial activity against Escherichia coli and Staphylococcus aureus were assessed by spectrophotometric assays and the agar diffusion method, respectively. Highest extraction yields were obtained using alkaline extraction (14.32%) and ultrasound-assisted extraction (UAE) (13.86%), followed by ethanol extraction (12.74%). Minimum inhibitory concentration (MIC) for P-βCD was 0.04 mg/mL, and the minimum bactericidal concentration (MBC) was 0.32 mg/mL against S. aureus. These results suggest a strong inhibitory capacity at low concentrations and the potential incorporation of these extracts into bio-based antimicrobial biomaterials. Full article

Glucose oxidase (GOD) is a natural enzyme with antioxidant and antimicrobial properties but its effects on sows remain insufficient. This study investigated the effects of dietary GOD supplementation during gestation on inflammatory response, antioxidant capacity, immune function, and gut microbiota of farrowing sows. Twenty-four primiparous sows were randomly assigned to two groups and fed a basal diet or a basal diet supplemented with GOD (300 mg/kg diet) from gestation day 30 to farrowing. GOD supplementation significantly increased triglyceride, superoxide dismutase, and immunoglobulin M levels (p < 0.05), and significantly decreased alanine aminotransferase and interleukin-6 levels in serum (p < 0.05); significantly reduced placental interleukin-1β, malondialdehyde and tumor necrosis factor-α concentrations and NF-κB gene expression (p < 0.05), and elevated glutathione peroxidase activity and relative mRNA expressions of Nrf2, HO-1, GPX1 and SOD2 (p < 0.05). Moreover, GOD supplementation altered the fecal microbial community structure (p < 0.05), significantly reducing Clostridium, dgaA-11_gut_group, Bacteroides, and Prevotellaceae_NK3B31_group abundance (p < 0.05), while enriching Lachnospira, unclassified_f_Erysipelotrichiaceae, and Anaerostipes (p < 0.05). Collectively, 300 mg/kg glucose oxidase supplementation during mid-to-late gestation improved the health status of farrowing sows by improving nutrient utilization, immune function and antioxidant capacity, and altering fecal microbial structure and relative abundances. Full article

This study investigated the epidemiology, antimicrobial resistance, and transmission risks of β-lactamase, cefotaxime-hydrolyzing, Munich (bla_CTX-M)-positive Escherichia coli (CTX-M-EC) in large-scale pig farms in Jiangxi Province (China). In total, 278 samples (manure, wastewater, drinking water, and flies) were collected. CTX-M-EC strains were isolated and analyzed using antimicrobial susceptibility testing, resistance gene profiling, multilocus sequence typing, and genetic environment analysis with gene transfer assessed by transduction experiments. Twenty-seven CTX-M-EC strains (9.71%) were isolated, all exhibiting multi-drug resistance with 100% resistance to cefotaxime, ciprofloxacin, and tetracycline, and >90% resistance to ceftazidime, florfenicol, and trimethoprim-sulfamethoxazole. Four bla_CTX-M subtypes were identified. bla_CTX-M-55 was the predominant subtype (70.37%) and was distributed across diverse sequence types and serotypes. Each strain harbored multiple antibiotic resistance genes, plasmids, and virulence genes. Mobile elements such as ISEcp1 and IS26 were detected surrounding the bla_CTX-M gene, and 96.29% of strains successfully transferred the bla_CTX-M gene via transduction. Clones highly homologous to pig manure strains were detected in flies and sewage, suggesting that this resistance gene can spread between animals, the environment, and vectors. These findings highlight the high transmission risk of bla_CTX-M and underscore the need for rational antibiotic use, waste management, and vector control within a One Health framework. Full article

Infectious diseases remain a major global health challenge, driven by antimicrobial resistance, pathogen persistence, and the limited integration of mechanistically innovative therapeutic approaches. Emerging evidence indicates that epigenetic regulation is fundamental to host–pathogen interactions, influencing transcriptional programmes associated with virulence, immune evasion, stress adaptation, and phenotypic plasticity. In organisms such as bacteria, parasites, and intracellular pathogens, including Mycobacterium tuberculosis and Plasmodium falciparum, chromatin-associated regulators and DNA-modifying enzymes have been identified as dosage-sensitive determinants of infection outcomes. Traditional strategies focus primarily on occupancy-driven enzymatic inhibition. In contrast, targeted protein degradation (TPD) introduces an event-driven pharmacological paradigm in which transient ligand engagement triggers sustained depletion of regulatory proteins. Platforms such as proteolysis-targeting chimeras (PROTACs) and BacPROTACs exemplify the ability to exploit host and pathogen proteolytic systems, thereby expanding the druggable proteome beyond conventional small-molecule targets. This review examines the relationship between epigenetic regulation and pathogen survival, highlights recent advances in degradation technologies, and discusses conceptual and translational challenges in implementing TPD in antimicrobial and antiparasitic drug discovery. Full article

Background/Objectives: The purpose of this study was the chemical design, synthesis, and evaluation of the antimicrobial and antibiofilm potentials of 20 novel thiazolyl-methylthio-thiadiazole hybrid compounds (6a–j and 8a–j). Methods: The compounds were designed as structural analogues of halicin with two points of variation and were synthesized through a process with multiple condensation steps. The compounds were evaluated in vitro through MIC determinations for the antimicrobial activity and percentage of biofilm inhibition, and in silico, respectively, through molecular docking, druggability, and ADMETox prediction. A 2D-QSAR study was conducted for antimicrobial activity using the Free-Wilson model. Results: In terms of antibacterial activity, all compounds displayed important activity on the tested strains (MICs = 15.62–250 μg/mL), except against Staphylococcus aureus. Regarding the antifungal activity, the effect against Candida albicans was similar to fluconazole in most cases (MIC = 15.62 μg/mL). With respect to the antibiofilm activity, the most effective activity was registered against the Pseudomonas aeruginosa biofilm. The in vitro results for the antibacterial activity against Escherichia coli were correlated with the observations drawn in the molecular docking study on the ATPase domain of the GyrB subunit of E. coli. The in silico predictions of the molecular properties concluded that all compounds have good druggability properties, while the ADMETox predictions concluded that the compounds could have low gastrointestinal absorption and blood–brain barrier permeation capacity, but raised safety flags (e.g., hepatotoxicity and high acute oral toxicity). The 2D-QSAR study concluded that the thiazolyl-methylthio-thiadiazole scaffold had the highest contribution to antimicrobial activity in almost all cases. Conclusions: The two series of compounds highlight the impact of structural modulations of the scaffold and its substituents on the investigated biological activities. Full article

Antimicrobial resistance (AMR) represents a major global health threat, largely driven by antibiotic overuse and the protective role of bacterial biofilms. Quorum sensing (QS), a bacterial communication system regulating virulence and biofilm formation, has emerged as a promising therapeutic target. Quorum quenching (QQ), which disrupts QS without directly inhibiting bacterial growth, is considered a potential anti-virulence strategy that may reduce selective pressure for resistance. This review critically evaluates recent advances in QQ research, focusing on its clinical applicability, limitations, and risks. We analyzed studies from the last five years involving natural compounds, synthetic molecules, nanoparticles (NPs), and combination therapies targeting key pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus in models of lung diseases, mainly cystic fibrosis, chronic wounds, burns, and implant-associated infections. While numerous compounds demonstrate significant in vitro anti-biofilm and anti-virulence activity, major challenges remain, including limited in vivo validation, pharmacokinetic constraints, toxicity concerns, microbiome disruption, and the potential development of tolerance or functional resistance. Although QQ offers a promising adjunctive approach to conventional antibiotics, its long-term clinical feasibility requires comprehensive evaluation of evolutionary dynamics, host–microbe interactions, and safety profiles. Full article

Background/Objectives: The accumulation of unused and expired pharmaceuticals in households is a growing public health concern with implications for patient safety, rational drug use, and environmental health. However, systematic risk characterization integrating clinical and environmental perspectives at the community level remains limited, particularly in low- and middle-income settings. This study aimed to develop and apply a composite risk index, grounded in an eco-pharmacovigilance framework, for the assessment of health risks associated with accumulated household pharmaceuticals in southeastern Mexico. Methods: A cross-sectional study was conducted in 526 randomly selected households using stratified sampling. Guided in-home medication inventories were performed with participant collaboration, and pharmaceuticals were classified according to the Anatomical Therapeutic Chemical (ATC) system. A composite risk index (CRI = Fr × PR) was developed within an eco-pharmacovigilance framework. The frequency of accumulation (Fr) for each therapeutic group was multiplied by a potential risk score (PR) derived through a structured multidisciplinary expert consensus process integrating clinical toxicity, environmental persistence, and antimicrobial resistance potential. Results: A total of 2184 pharmaceutical units were recorded during the household inventories, of which 28.7% were expired. Expired medications were primarily retained rather than actively used, representing a latent risk for inappropriate self-medication and accidental exposure. The therapeutic groups with the highest CRI values were antihypertensives (CRI = 42.3), antidiabetics (CRI = 37.8), and antibiotics (CRI = 31.5), indicating a relatively higher contribution within the composite risk index framework to overall household pharmaceutical risk. These findings highlight priority therapeutic groups driven by the combined effect of high accumulation frequency, distinct accumulation patterns, and intrinsic hazard. Conclusions: Household pharmaceutical accumulation can be characterized using a composite, eco-pharmacovigilance-based approach that integrates exposure and hazard dimensions. The proposed framework functions as a prioritization tool rather than a precise quantitative measure, enabling the identification of therapeutic groups requiring targeted intervention. Findings should be interpreted as indicative of relative risk patterns rather than precise estimates, given the exploratory design and guided data collection approach. The proposed framework provides a practical tool for prioritizing interventions aimed at improving rational drug use, reducing accumulation, and mitigating environmental impact. Further validation in diverse settings is warranted to strengthen its applicability. Full article

Parasitic plants represent a unique group of angiosperms that extract nutrients from host plants through specialized structures called haustoria. With over 4750 recognized species, these plants vary in their dependence on hosts, classified as holoparasites (completely non-photosynthetic) or hemiparasites (partially photosynthetic). Despite their parasitic lifestyle, these plants contribute significantly to ecological stability by regulating plant communities. Some parasitic species, such as Striga and Orobanche, are major agricultural pests, while others, including Cistanche and Cynomorium, are valued for their medicinal properties. Parasitic plants in general are rich in secondary metabolites with potential pharmacological significance. These compounds, including alkaloids, phenolics, and terpenoids, display antimicrobial, anticancer, and immunomodulatory effects. Mistletoe (Viscum album L.) produces lectins and viscotoxins, which exhibit cytotoxic and immune-stimulating properties. Traditional medicine has long utilized parasitic plants, and modern pharmacological research continues to uncover their potential in drug development. However, an intriguing question arises: whether they are superior in any way to their non-parasitic counterparts, or just received more attention due to their unique appearance. Understanding the unique chemistry of parasitic plants provides insights into their ecological role and offers opportunities for advancements in medicine and agriculture. Full article

Hematologic malignancies arise and progress within a systemic ecosystem in which the gut microbiota is an increasingly recognized, partially modifiable component. Across acute leukemias, chronic lymphocytic leukemia, plasma cell disorders, lymphomas, and clonal myeloid neoplasms, human studies consistently report reduced microbial diversity, depletion of barrier-supportive, short-chain fatty acid-producing commensals, and enrichment of Gram-negative, pro-inflammatory, or hospital-adapted taxa. These alterations are associated with pre-leukemic clonal expansion, adverse genetic and immunological features, progression from precursor conditions, and inferior outcomes after chemotherapy, immunochemotherapy, chimeric antigen receptor T-cell therapy, and allogeneic hematopoietic stem cell transplantation. Mechanistic work in animal models and ex vivo systems demonstrates that microbiota-derived signals and metabolites—including Th17/IL-17-skewing consortia and the lipopolysaccharide intermediate ADP heptose sensed by the cytosolic receptor ALPK1—can actively modulate hematopoietic stem and progenitor cell fitness, inflammatory circuits, and malignant cell survival, supporting a causal role in disease biology. At the same time, major knowledge gaps remain because most human cohorts are small, single-center, and cross-sectional, frequently rely on 16S rRNA profiling, and are vulnerable to dietary, geographic, and treatment-related confounding. Within this context, three translational domains appear particularly promising: pharmaco-microbiomics, microbiome-informed risk stratification, and rational microbiota-targeted interventions, particularly diet-based strategies and antimicrobial stewardship. Here, we provide an integrated, disease-spanning synthesis of these data, emphasizing clonal hematopoiesis and myeloid neoplasms as emerging examples of microbiota–marrow crosstalk and outlining practical priorities for embedding microbiome science into future hematologic trials. Routine microbiome profiling or empiric microbiota-directed therapies cannot yet be recommended in everyday hematology practice, but integrating microbiome science into prospective therapeutic and transplant trials offers a realistic path to improved disease modeling, biomarker development, and rational adjunctive strategies to enhance outcomes for patients with hematologic malignancies. Full article