Search Results (14,765)

Biofilms are microbial communities embedded in an extracellular matrix that facilitates their attachment to surfaces. This lifestyle provides advantages to pathogenic bacteria, including increased survival in the presence of antibiotics and an enhanced capacity to develop resistance. Once a biofilm is established, infections get difficult to eradicate and frequently become chronic. There is, therefore, an urgent need to develop novel strategies to counteract biofilm-associated antibiotic resistance. Here, we developed a method to monitor the evolution of antimicrobial resistance, aiming to evaluate novel drugs against bacterial resistance to antibiotics. We validated this methodology using an RNase chimera with antibiofilm activity and a reported ability to hinder colistin resistance in planktonic cultures of Acinetobacter baumannii (A. baumannii). We assessed the emergence of resistance in A. baumannii biofilms by repeated cycles of colistin exposure. This method not only preserves biofilm structure throughout treatment but also enables controlled induction of resistance acquisition while monitoring antimicrobial efficacy. Although the RNase enhanced the antibiotic’s activity against biofilms by reducing by 50% the effective dose, it did not prevent the emergence of colistin resistance, indicating that the protein may use distinct mechanisms against planktonic and biofilm communities. Nonetheless, our findings highlight the potential of this methodology for evaluating antibiotic-adjuvant candidates to combat antibiotic resistance in biofilms. Full article

The transition to a circular bioeconomy enhances the valorization of agricultural by-products. Hawthorn leaves (Crataegus spp.), generated in large quantities from orchard maintenance, represent a promising yet underutilized biomass. This comprehensive narrative review synthesizes recent advances regarding their bioactive compounds, extraction methods, and applications. A systematic literature search was conducted to identify relevant studies. The analysis reveals that hawthorn leaves are rich in polyphenols (e.g., flavonoids, procyanidins), with their content often exceeding that found in fruits. Modern “green” extraction techniques (e.g., ultrasound- and microwave-assisted) demonstrate superior efficiency in recovering these thermolabile compounds compared to conventional methods. The broad spectrum of associated biological activities—including antioxidant, cardioprotective, neuroprotective, antimicrobial, and insecticidal effects—underpins their potential in nutraceuticals, cosmetics, and functional foods. Crucially, this review highlights the significant promise of hawthorn leaf extracts as a source for developing natural, plant-based biopesticides, aligning with sustainable agriculture and integrated pest management principles. To fully realize this “waste-to-wealth” potential, future research should prioritize the scaling of eco-friendly extraction, field trials for crop protection efficacy, and the standardization of extracts. Full article

Background/Objectives: Oleuropein is a bioactive phenolic compound from olive leaves with antimicrobial and antioxidant activity. This study aimed to develop a sprayable oral gel containing an oleuropein-rich aqueous extract and to evaluate its pharmaceutical performance antimicrobial efficacy and in ovo biological response. Methods: Oleuropein content was quantified using a validated chromatographic method. Polymeric systems were screened to select an optimized sprayable formulation. Physicochemical stability, dose uniformity, and antimicrobial activity against major cariogenic bacteria were evaluated. In ovo biological evaluation was conducted using the chick chorioallantoic membrane angiogenesis model together with histopathological examination of embryonic heart and liver tissues. Results: Oleuropein content was determined as 288.6 µg/mL in the olive leaf extract and 255.1 µg/mL in the final formulation. The optimized oral spray showed stable physicochemical properties, with pH maintained at 6.90 ± 0.02 and no relevant changes in viscosity during storage. The mean delivered dose per actuation was 0.128 ± 0.015 g, corresponding to 32.6 µg oleuropein per spray. The formulation exhibited inhibitory activity against all tested cariogenic microorganisms, with MIC values ranging from 13.3 to 170.7 µg/mL and MBC values generally two-fold higher. In the CAM assay, significant concentration- and time-dependent antiangiogenic effects were observed after 24–48 h at moderate and higher concentrations. Histopathological evaluation revealed dose-dependent acute degenerative and congestive changes in heart and liver tissues without evidence of fibrosis or steatosis. Conclusions: The oleuropein-based sprayable oral gel is a promising localized delivery system with adequate stability dose uniformity and antimicrobial efficacy. In ovo findings provide a conservative assessment of systemic exposure and support further development for oral biofilm and caries-related applications. Full article

Background: Xanthohumol (XN), a prenylated chalcone flavonoid derived from hops (Humulus lupulus), is increasingly recognized as a highly pleiotropic natural compound. Objective: We aimed to structure XN’s mechanistic hierarchy with emerging translational relevance across disease areas. Methods: We performed a comprehensive and integrative literature review of XN for its biological and translational effects across cancer, metabolic, neurological, cardiovascular, hepatic, renal, and dermatological disorders. Results: Mechanistically, XN exerts diverse bioactivities by inhibiting major pro-oncogenic and pro-inflammatory pathways, such as NF-κB, PI3K/Akt/mTOR, STAT3, HIF-1α, and selective MAPK cascades, while activating cytoprotective signaling, such as the Nrf2/ARE and AMPK pathways. Through these coordinated actions, XN modulates redox homeostasis, mitochondrial integrity, apoptosis, autophagy, ferroptosis, and inflammatory responses. In oncology, XN demonstrates broad-spectrum anticancer activity in preclinical models by inhibiting proliferation; inducing cell cycle arrest and apoptosis; suppressing epithelial–mesenchymal transition, angiogenesis, and metastasis; and restoring chemosensitivity in resistant cancers, including breast, lung, gastric, liver, and head-and-neck carcinomas. Beyond cancer, XN exhibits multi-organ protective bioactivities through antioxidative, antimicrobial, antiviral, and anti-inflammatory activities; inhibition of ferroptosis and excitotoxicity; and preservation of mitochondrial integrity. It shows beneficial effects in preclinical models of Parkinson’s disease, Alzheimer’s disease, hepatic steatosis and fibrosis, renal ischemia–reperfusion injury, cardiovascular dysfunction, skin photoaging, and atopic dermatitis. Human subject studies demonstrate that XN is safe and well tolerated, with observed reductions in oxidative DNA damage and inflammatory cytokine release. Recent advances in micellar formulations have improved XN’s systemic bioavailability and thus its translational feasibility. Conclusions: In summary, XN is a safe, multifunctional natural compound with strong potential for modulating disease-relevant biological pathways associated with cancer, neurodegenerative diseases, metabolic disorders, and inflammatory skin conditions. Continued efforts to enhance its bioavailability and conduct rigorous clinical trials are essential to fully establish its clinical relevance in patient populations. Full article

This study explores the taxonomic diversity, metabolic profile, and bioactivity of marine-derived actinomycetes isolated from sediments collected off the coast of Lisbon and Setúbal Peninsula, Portugal. The combined use of two sediment pre-treatments (heat shock and dry overnight) and four growth media with varying nutrient concentrations revealed that formulations 10% A1 and SWA were most effective for recovering diverse actinomycetes, including rare Actinomadura, resulting in a total of 142 cultivable strains closely related to 47 phylogenetic distinct species dominated by Streptomyces and Micromonospora. Antimicrobial screening against methicillin-resistant Staphylococcus aureus (MRSA, COL) and Escherichia coli (K12) identified 22 bioactive strains, with strain PTS-083 exhibiting the strongest activity against MRSA (MIC = 1.95 µg/mL) and a 98.30% 16S rRNA gene identity to S. chumphonensis, highlighting it as a strong candidate for further metabolite and genomic studies. Cytotoxicity assays against HCT-116 human colorectal adenocarcinoma cells revealed eight bioactive strains with potent anticancer activity for extracts from strains related to S. sundarbansensis, S. violaceorubidus, and S. aculeolatus (IC₅₀ < 0.005–5.08 µg/mL). Untargeted LC-MS/MS metabolomic analysis uncovered a wide array of secondary metabolites, including macrolides, siderophores, fatty acids, and cyclic peptides. Comparative analyses with other Portuguese coastal studies revealed both shared and distinctive metabolomic profiles, emphasizing the importance of exhaustive sampling, even at nearby locations, as their localized environmental conditions can influence metabolic diversity. These findings highlight Portugal’s coastal sediments as a rich and underexplored source of novel actinomycetes and bioactive compounds with promising pharmaceutical applications. Exhaustive sampling of marine sediment actinomycete communities, even at nearby locations, is crucial for discovering unique metabolites with potential biotechnological value. Full article

Smart hydrogels, which combine hydrogel properties such as biocompatibility, high drug loading capacity, and injectability while being responsive to external stimuli, are a subclass of smart materials. Smart hydrogels respond to effects that are not harmful to the human body, such as temperature, pH, light, and biomolecules. Furthermore, some smart hydrogels possess dual-responsive properties or can be multifunctional, exhibiting both adhesive and responsive behavior to external stimuli. Smart hydrogels have made groundbreaking advances in the field of biomedical. They have been improved through structural modifications and by gaining the ability to be multi-responsive. Controlling drug release and biofilm disruption by using these smart hydrogels is one of the efficient strategies to reduce antimicrobial resistance and the number of deaths caused by microbial diseases. In this review, the preparation of smart hydrogels, their various types and applications in the treatment of microbial diseases were investigated. Full article

Polymer-based bioactive composites are one of the most rapidly advancing areas in contemporary regenerative medicine. This review aims to identify major trends and knowledge gaps in the development of bioactive polymer composites and examine their translational relevance from a materials design perspective, with a specific focus on synthetic thermoplastic polymer matrices suitable for load-bearing bone scaffold applications and filament-based additive manufacturing. A total of 546 publications spanning 2016–2025 were screened, with 106 selected according to predefined relevance criteria. Bibliometric and content analyses were performed to delineate the primary research trajectories of bioactive composite materials. The results revealed that the majority of studies focused on composites comprising synthetic aliphatic polyesters, primarily polylactic acid (PLA) or polycaprolactone (PCL), reinforced with hydroxyapatite (HA) or bioactive glass (BG), which confer osteoconductivity but rarely achieve multifunctionality. Antimicrobial agents, ion-releasing components, and naturally derived bioactive molecules—associated with biointeractive functionalities and reported effects related to osteogenesis, angiogenesis, and immune modulation—are significantly underrepresented. Fewer than 20% of the investigated studies include in vivo validation, underscoring considerable scope for further preclinical and translational research. This work consolidates current trends in synthetic bioactive polymer composite design and identifies critical directions for future research. The findings of this review provide a structured framework to support the selection of composite fabrication and modification strategies, functional additives, and targeted biological functionalities for next-generation, load-bearing bone tissue engineering materials. Full article

Background/Objectives: In food-producing animal (FPA) environments, healthy animals can act as reservoirs of potentially pathogenic Escherichia coli, which can be transmitted through the food chain to humans. This study aimed to evaluate cloacal E. coli in healthy Sicilian lambs subjected to an experimental feeding regimen by assessing bacterial levels, antimicrobial resistance, virulence traits, and the clonal relationships, as well as the impact of a pistachio skin as an agro-industrial by-product supplement during a 58-day feeding trial. Methods: A total of 295 E. coli isolates from the control (CTRL) and treatment (Treated) groups at initial time (T0) and final time (T1) were phenotypically and genotypically characterized using Kirby–Bauer antimicrobial testing, multiplex PCR for virulence genes, and PFGE for clonal analysis. Results: The feeding regimen did not significantly influence the prevalence, abundance, or virulence of the E. coli isolates. Shiga toxin-producing E. coli (STEC) were the most common pathotype, mainly carrying the stx1 gene, while the Enteroinvasive (EIEC) type was detected only sporadically. Enteropathogenic E. coli (EPEC) predominated at T0, while enteroaggregative E. coli (EAEC) at T1, and enterotoxigenic E. coli (ETEC), initially prevalent in Treated samples, disappeared by T1. Antimicrobial resistance profiles varied among isolates, with the highest resistance observed in the CTRL group. However, both groups exhibited high resistance to streptomycin, and 9% of CTRL isolates were multidrug resistant. A notable reduction in overall resistance rates, especially in the Treated group, was observed, indicating a dietary effect on the E. coli resistome. PFGE genotyping showed high genetic diversity, with resistance traits more frequently detected than virulence factors. Conclusions: This study highlights that healthy lambs serve as reservoirs for potentially human-pathogenic E. coli and suggests that dietary regimes could effectively reduce antibiotic resistance. Full article

Lactic acid bacteria (LAB) are widely used in food systems; among them, bacteriocin-producing strains have attracted attention for their potential in the biopreservation of dairy products. This study started from the detection of bacteriocin-encoding genes in eight probiotic Leuconostoc mesenteroides subsp. mesenteroides strains, previously isolated, identified, and characterized for antimicrobial activity. Results confirmed the presence of bacteriocin genes across the strains, with Ln.F5 harboring both mesB and lcnA genes, and three other strains, including the Ln.M14 strain, exclusively carrying the lcnA gene. The two strains, Ln.F5 and Ln.M14, were used, in single and mixed cultures, for the first time, as adjunct cultures in a model cheese. Their impact against Listeria spp., Staphylococcus aureus, Escherichia coli, Micrococcus luteus, and Brochothrix thermosphacta, and on volatile organic compounds (VOCs), during ripening and storage, was evaluated. Results showed high viability (9.2 Log CFU/g) of Leuconostoc spp. in model cheese, up to 60 days of storage, and Pulsed-Field Gel Electrophoresis (PFGE) profiles of the re-isolated bacteria confirmed the survival of the added strains. Furthermore, results indicated the inhibition of E. coli and Listeria spp. started from the 15th day of ripening in samples differently inoculated with the two Leuconostoc strains. Listeria spp. was completely inhibited starting from 15 days by Ln.M14, in single culture. The complete inhibition of S. aureus, M. luteus, and B. thermosphacta was detected after 30 days of ripening in samples differently inoculated with Ln.F5 and Ln.M14. The VOC analyses revealed more complex aromatic profiles in samples inoculated with Leuconostoc strains, which, along with the development of cheese eyes, confirmed the effect of the Leuconostoc strains in enhancing quality traits of cheeses. Full article

Global health faces unprecedented challenges driven by communicable diseases, which are increasingly amplified by persistent health inequities, the impact of climate change, and the speed of emerging crises. Prevention is not merely a component but the foundational strategy for an effective, sustainable, and fiscally responsible public health response. This paper delves into the pivotal role of core prevention levers: robust vaccination programs, stringent hygiene standards, advanced epidemiological surveillance, and targeted health education. We detail how contemporary technological advancements, including Artificial Intelligence (AI), big data analytics, and genomics, are fundamentally reshaping infectious disease management, enabling superior predictive capabilities, faster early warning systems, and personalized prevention models. Furthermore, we thoroughly examine the imperative of integrating the One Health approach, which formally recognizes the close, interdependent links between human, animal, and environmental health as critical for combating complex threats like zoonoses and Antimicrobial Resistance (AMR). Despite significant scientific progress, persistent socio-economic disparities, the pervasive influence of health-related misinformation (infodemics), and structural weaknesses in global preparedness underscore the urgent need for decisive international cooperation and equitable financing models. We conclude that only through integrated, multidisciplinary, and resource-equitable strategies can the global community ensure effective prevention, mitigate severe socio-economic disruption, and successfully build resilient healthcare systems capable of withstanding future global health threats. Full article

Growing limitations on the use of in-feed antibiotics have accelerated the search for functional feed additives capable of supporting animal health and productivity under antibiotic-free production systems. Postbiotics, defined as non-viable microbial products or metabolic byproducts, and phytogenics, which are plant-derived bioactive compounds, have emerged as promising alternatives due to their stability and biological activity. Recent advances in the application of postbiotics and phytogenics in monogastric and ruminant nutrition are summarized, with emphasis on their mechanisms of action, synergistic effects, and impacts on gut health, immune function, and growth performance. Postbiotics modulate the gut microbiota, enhance epithelial barrier integrity, and regulate immune signaling, whereas phytogenic compounds provide antimicrobial, antioxidant, and digestive-stimulant effects. Available evidence suggests that combined strategies can enhance efficacy, particularly under production-related stress. Key challenges related to formulation, dose–response relationships, stability, and regulatory classification are discussed together with emerging omics-based approaches that support precision formulation. Overall, integration of multi-omics evidence with formulation and regulatory considerations supports the practical use of postbiotics and phytogenics in commercial livestock systems. Full article

Microcin C7 (McC7) is a ribosomally synthesized antimicrobial peptide that has emerged as a promising candidate due to its dual antibacterial and immunomodulatory activities. This study evaluated the preventive effect of McC7 against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. An immunosuppression model was established by intraperitoneal CTX injection in mice, which were randomly allocated into five groups (n = 15): a negative control, a CTX model group, and three McC7 treatment groups receiving dietary McC7 at 100, 200, or 400 mg/kg both before and during CTX exposure. Body weight and feed intake were monitored throughout the study. Organ indices, serum biochemical parameters, immune and antioxidant markers, and intestinal morphology were assessed. Splenic T-cell subsets were analyzed by flow cytometry, and gut microbiota composition was evaluated by 16S rRNA sequencing. McC7 supplementation significantly attenuated the CTX-induced reduction in body weight, feed intake, and organ indices, ameliorated markers of hepatic and renal injury, and restored the splenic CD4⁺/CD8⁺ T-cell ratio. McC7 enhanced intestinal mucosal barrier integrity, increased the abundance of beneficial bacteria such as Candidatus Arthromitus and ASF356, and reduced the abundance of the potentially pathogenic genus Bilophila. In conclusion, our results demonstrate that McC7 alleviates CTX-induced immunosuppression by regulating T-cell differentiation, maintaining cytokine homeostasis, and modulating gut microbial composition to support intestinal health. Full article

Background: Conservative management of port-related bacteremia often includes locally administered antimicrobials, known as antimicrobial lock therapy (ALT). Current guidelines recommend daily replacement of antimicrobial lock solutions (ALSs). We aimed to evaluate whether ALSs could remain effective with extended dwell times of up to 10 days. Methods: In this randomized clinical trial, patients with noninfected, recently implanted ports were assigned to one of five ALS dwell-time groups, ranging from 1 to 10 days. Each ALS contained heparin plus an antimicrobial at standard intraluminal concentrations: vancomycin 2 mg/mL, teicoplanin 10 mg/mL, linezolid 1.8 mg/mL, daptomycin 5 mg/mL, or tigecycline 4.5 mg/mL. The primary endpoint was the time at which intraluminal drug concentrations decreased below 1 mg/mL (ClinicalTrials.gov NCT01592032). Results: Vancomycin and linezolid concentrations fell significantly below 1 mg/mL after 3 days of dwell time. Daptomycin and tigecycline concentrations decreased significantly after 7 days but remained above 1 mg/mL. Teicoplanin concentrations did not decline significantly after 7 days. Conclusions: Optimal ALS dwell time depends on the antimicrobial agent. Vancomycin and linezolid locks require daily replacement, whereas daptomycin, tigecycline, and teicoplanin locks maintain therapeutic concentrations for up to 7 days. These findings support individualized ALS replacement strategies, potentially reducing the need for daily interventions. Full article

Background/Objectives: Potential drug–drug interaction (pDDI) refers to the co–administration of two or more drugs that interact with each other and may have therapeutic effects. Increasing rates of polypharmacy with age increase the risk of pDDIs in geriatric patients. This multicenter study aims to provide real–world data on the incidence of pDDI associated with antimicrobial therapy in hospitalized older adults. Methods: The study screened all hospitalized patients, including those aged 65 years and older. Using the Lexicomp^® Drug Interaction Online Database, researchers screened for pDDIs among all medications taken by patients. Results: 663 (24.0%) aged 65 and over were included in the study. Polypharmacy was present in 64.9%, and hyperpolypharmacy was present in 10.0% of the cases. 480 (72.4%) of the cases used antimicrobial therapy. The mean total number of drugs and antimicrobials used per case was 5.86 and 1.02, respectively. A total of 372 antimicrobial–related pDDIs were detected, and at least one antimicrobial–related pDDI was identified in 202 (42%) patients receiving antimicrobials. Ciprofloxacin (73.3%), clarithromycin (58.3%), and colistin (26.3%) had the highest numbers of D–type pDDIs. The antimicrobials with the highest incidence of X–type pDDIs were metronidazole (23.6%) and clarithromycin (8.3%), respectively. The logistic analysis found a significant association between antimicrobial–related pDDIs and an increase in the number of drugs, length of hospital stays, and ID departments. Conclusions: PDDI rates associated with antimicrobials, like the high pDDI rates associated with all drugs, support the literature. Therefore, strategies should be developed to reduce the risk of pDDI when prescribing antimicrobials to geriatric patients. Full article

Klebsiella pneumoniae is a prominent pathogen implicated in a wide range of infections, including pneumonia, urinary tract infections, and septicemia. Its ability to acquire and disseminate antibiotic resistance, coupled with the rising prevalence of hypervirulent strains, represents a significant public health threat. Understanding the molecular basis of drug resistance can guide the design and development of effective treatment strategies. Antimicrobial resistance (AMR) in these bacteria is a complicated process and cannot be attributed to a single resistance mechanism. K. pneumoniae develops resistance to antibiotics through a variety of mechanisms, ranging from single molecular mechanisms to complex interactions, where molecular synergy exacerbates resistance. This review summarizes the current understanding of the molecular mechanisms that contribute to the drug resistance and virulence of this pathogen. Key antibiotic resistance mechanisms include drug inactivation via B-lactamases and carbapenemases, membrane remodeling, efflux pump systems, such as AcrAB-TolC and OqxAB, and biofilm formation facilitated by quorum sensing. Additionally, the role of ribosomal changes in resistance is highlighted. This review also examines the mechanisms of virulence, emphasizing fimbriae, iron acquisition systems, and immune evasion strategies. Understanding these mechanisms of drug resistance and virulence is crucial for remodeling existing antibiotics and developing new therapeutic strategies. Full article