Search Results (262)

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

Soil degradation resulting from intensive agricultural practices, the excessive use of agrochemicals, and climate-induced stresses has significantly impaired soil fertility, disrupted microbial diversity, and reduced crop productivity. Plant growth-promoting bacteria (PGPB) represent a sustainable biological approach to restoring degraded soils by modulating plant physiology and soil function through diverse molecular mechanisms. PGPB synthesizes indole-3-acetic acid (IAA) to stimulate root development and nutrient uptake and produce ACC deaminase, which lowers ethylene accumulation under stress, mitigating growth inhibition. They also enhance nutrient availability by releasing phosphate-solubilizing enzymes and siderophores that improve iron acquisition. In parallel, PGPB activates jasmonate and salicylate pathways, priming a systemic resistance to biotic and abiotic stress. Through quorum sensing, biofilm formation, and biosynthetic gene clusters encoding antibiotics, lipopeptides, and VOCs, PGPB strengthen rhizosphere colonization and suppress pathogens. These interactions contribute to microbial community recovery, an improved soil structure, and enhanced nutrient cycling. This review synthesizes current evidence on the molecular and physiological mechanisms by which PGPB enhance soil restoration in degraded agroecosystems, highlighting their role beyond biofertilization as key agents in ecological rehabilitation. It examines advances in nutrient mobilization, stress mitigation, and signaling pathways, based on the literature retrieved from major scientific databases, focusing on studies published in the last decade. Full article

Cinnamic acid, an organic acid naturally occurring in plants of the Cinnamomum genus, has been highly valued for its medicinal properties in numerous ancient Chinese texts. This article reviews the chemical composition, pharmacological effects, and various applications of cinnamic acid and its derivatives reported in publications from 2016 to 2025, and anticipates their potential in medical and industrial fields. This review evaluates studies in major scientific databases, including Web of Science, PubMed, and ScienceDirect, to ensure a comprehensive analysis of the therapeutic potential of cinnamic acid. Through systematic integration of existing knowledge, it has been revealed that cinnamic acid has a wide range of pharmacological activities, including anti-tumor, antibacterial, anti-inflammatory, antidepressant and hypoglycemic effects. Additionally, it has been shown to be effective against a variety of pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, and foodborne Pseudomonas. Cinnamic acid acts by disrupting cell membranes, inhibiting ATPase activity, and preventing biofilm formation, thereby demonstrating its ability to act as a natural antimicrobial agent. Its anti-inflammatory properties are demonstrated by improving oxidative stress and reducing inflammatory cell infiltration. Furthermore, cinnamic acid enhances metabolic health by improving glucose uptake and insulin sensitivity, showing promising results in improving metabolic health in patients with diabetes and its complications. This systematic approach highlights the need for further investigation of the mechanisms and safety of cinnamic acid to substantiate its use as a basis for new drug development. Particularly in the context of increasing antibiotic resistance and the search for sustainable, effective medical treatments, the study of cinnamic acid is notably significant and innovative. Full article

The increasing threat of antimicrobial resistance (AMR), along with the limited availability of new lead compounds in the drug development pipeline, highlights the urgent need to discover antimicrobial agents with innovative mechanisms of action. In this regard, metal complexes offer a unique opportunity to access mechanisms distinct from those of conventional antibiotics. Although iron (Fe) is an essential element for all forms of life, including pathogenic bacteria, it also poses a serious risk of cytotoxicity due to its redox activity, which can trigger the production of reactive oxygen species (ROS) via the Fenton reaction. This review highlights recent advances in the development of iron-based antimicrobial agents that harness the toxicity resulting from dysregulated iron uptake, thereby inducing bacterial cell death through oxidative stress. These findings may guide the development of effective treatments for pathogenic infections and offer new perspectives on leveraging redox chemistry of iron to combat the growing threat of global bacterial resistance. Full article

Aminoglycoside antibiotics are critical in clinical use for treating severe infections, but they can occasionally cause irreversible sensorineural hearing loss. To establish a rational pathway for otoprotectant discovery, we provide an integrated, three-tier methodology—comprising cell-model selection, transcriptomic analysis, and a gentamicin–Texas Red (GTTR) uptake assay—to guide the development of otoprotective strategies. We first utilized two murine auditory cell lines—UB/OC-2 and HEI-OC1. We focused on TMC1 and OCT2 and further explored the underlying mechanisms of ototoxicity. UB/OC-2 exhibited a higher sensitivity to gentamicin, which correlated with elevated OCT2 expression confirmed via RT-PCR and Western blot. Transcriptomic analysis revealed upregulation of PI3K-Akt, calcium, and GPCR-related stress pathways in gentamicin-treated HEI-OC1 cells. Protein-level analysis further confirmed that gentamicin suppressed phosphorylated Akt while upregulating ER stress markers (GRP78, CHOP) and apoptotic proteins (cleaved caspase 3, PARP). Co-treatment with PI3K inhibitors (LY294002, wortmannin) further suppressed Akt phosphorylation, supporting the role of PI3K-Akt signaling in auditory cells. To visualize drug entry, we used GTTR to evaluate its applicability as a fluorescence-based uptake assay in these cell lines, which were previously employed mainly in cochlear explants. Sodium thiosulfate (STS) and N-acetylcysteine (NAC) significantly decreased GTTR uptake, suggesting a protective effect against gentamicin-induced hair cell damage. In conclusion, our findings showed a complex ototoxic cascade involving OCT2- and TMC1-mediated drug uptake, calcium imbalance, ER stress, and disruption of PI3K-Akt survival signaling. We believe that UB/OC-2 cells serve as a practical in vitro model for mechanistic investigations and screening of otoprotective compounds. Additionally, GTTR may be a simple, effective method for evaluating protective interventions in auditory cell lines. Overall, this study provides molecular-level insights into aminoglycoside-induced ototoxicity and introduces a platform for protective strategies. Full article

Background: Internationally, digital health interventions have increasingly been adopted within hospital settings. Optimising their clinical implementation requires user involvement, but there is a lack of evidence regarding how this should be done. Objectives: This study was carried out to understand the acceptability and usability of a prototype Digital Antibiotic Review Tracking Toolkit and identify modifications required to optimise it ahead of a trial. Methods: The optimisation process involved online semi-structured interviews with a purposive sample of fifteen healthcare professionals recruited from Scotland and England, along with three service users, to gather feedback on the prototype’s design, content and delivery. Participants’ negative views were specifically sought to identify adaptations needed to ensure that the intervention’s components aligned optimally with end-user needs. Data were analysed using Framework Analysis guided by the RE-AIM implementation science framework (Reach, Effectiveness, Adoption, Implementation, and Maintenance) to identify key themes. Results: Participants mostly voiced positive views regarding the prototype, finding it acceptable, feasible and engaging. They also identified concerns relating to its adoption, system functionality, accessibility and maintenance that needed to be addressed. Anticipated low adoption rates were linked to issues surrounding computer literacy. This detailed user feedback informed rapid adjustments to the intervention to enhance its acceptability, perceived future credibility and usability in hospitals. Conclusions: This novel study illustrates how to identify, modify and adapt a digital intervention quickly and efficiently using qualitative iterative methods. Findings highlight the critical importance of contextualising end-user experience with health interventions to facilitate future engagement, uptake, and long-term use. This study also demonstrates how core elements of the MRC framework can be operationalised to help refine prototype digital interventions pre-trial. Full article

Background/Objectives: Antibiotic contamination in water sources is a growing global concern, contributing to environmental degradation and the proliferation of antimicrobial resistance. Traditional treatment methods, such as advanced oxidation or high-pressure membrane processes, are often energy-intensive and economically unsustainable for large-scale or decentralized applications. This study explores the potential of two cost-effective, commercially available metal–organic frameworks (MOFs), ZIF-8 and F300, to improve the performance of membrane-based filtration–adsorption systems for removing tetracycline and sulfadiazine from water. Methods: Batch adsorption experiments were performed to evaluate the uptake capacities, kinetics, and isotherms of both MOFs toward the selected antibiotics. The membranes were modified using a low-cost silane-assisted deposition of MOF particles and tested in a microfiltration system. Removal efficiencies and water permeability were assessed and kinetic and isotherm models were applied to understand the adsorption mechanisms. Results: ZIF-8 showed superior adsorption performance, with maximum capacities of 442.2 mg/g for tetracycline and 219.3 mg/g for sulfadiazine. F300 was effective only for tetracycline. Membranes modified with ZIF-8 improved pharmaceutical removal by 187% (tetracycline) and 224% (sulfadiazine) compared to unmodified membranes. Although permeability decreased due to increased hydrophobicity, the materials and processes remained economically favorable. Conclusions: This study demonstrates that MOF-modified ceramic membranes, particularly those incorporating ZIF-8, offer a low-cost, scalable, and energy-efficient alternative for pharmaceutical removal from water. The approach combines strong environmental impact with economic viability, making it attractive for broader implementation in water treatment systems. Full article

The dramatic increase in antimicrobial resistance (AMR) in recent decades has created an urgent need to develop new antimicrobial agents and compounds that can modify and/or block bacterial resistance mechanisms. An understanding of these resistance mechanisms and how to overcome them would substantially assist in the development of new antibiotic chemotherapies. Bacteria may develop AMR through multiple differing mechanisms, including modification of the antibiotic target site, limitation of antibiotic uptake, active efflux of the antibiotic, and via direct modification and inactivation of the antibiotic. Of these, efflux pumps and the production of β-lactamases are the most common resistance mechanisms that render antibiotics inactive. The development of resistance-modifying agents (particularly those targeting efflux pumps and β-lactamase enzymes) is an important consideration to counteract the spread of AMR. This strategy may repurpose existing antibiotics by blocking bacterial resistance mechanisms, thereby increasing the efficacy of the antibiotic compounds. This review focuses on known phytochemicals that possess efflux pump inhibitory and/or β-lactamase inhibitory activities. The interaction of phytochemicals possessing efflux pumps and/or β-lactamase inhibitory activities in combination with clinical antibiotics is also discussed. Additionally, the challenges associated with further development of these phytochemicals as potentiating agents is discussed to highlight their therapeutic potential, and to guide future research. Full article

Nowadays, antimicrobial resistance (AMR) is a growing global health threat, with carbapenem-resistant Enterobacteriaceae (CRE) posing particular concern due to limited treatment options. In fact, CRE have been classified as a critical priority by the World Health Organization (WHO). Carbapenem resistance results from complex mechanisms, often combining the production of hydrolytic enzymes such as β-lactamases with reduced membrane permeability and efflux system induction. The Ambler classification is an effective tool for differentiating the characteristics of serine-β-lactamases (SβLs) and metallo-β-lactamases (MβLs), including ESβLs (different from carbapenemases), KPC, NDM, VIM, IMP, AmpC (different from carbapenemases), and OXA-48. Recently approved inhibitor drugs, such as diazabicyclooctanones and boronic acid derivatives, only partially address this problem, not least because of their ineffectiveness against MβLs. However, compared with taniborbactam, xeruborbactam is the first bicyclic boronate in clinical development with a pan-β-lactamase inhibition spectrum, including the IMP subfamily. Recent studies explore strategies such as chemical optimization of β-lactamase inhibitor scaffolds, novel β-lactam/β-lactamase inhibitor combinations, and siderophore–antibiotic conjugates to enhance bacterial uptake. A deeper understanding of the mechanistic properties of the active sites enables rational drug design principles to be established for inhibitors targeting both SβLs and MβLs. This review aims to provide a comprehensive overview of current therapeutic strategies and future perspectives for the development of carbapenemase inhibitor drug candidates. Full article

Controlled Environment Agriculture (CEA) offers a protected system for agricultural production; however, it remains vulnerable to diseases, particularly root diseases such as Pythium root rot and Fusarium wilt. Sustainable and eco-friendly agricultural practices using plant-beneficial microbes can help mitigate these harmful diseases. These microbes produce natural antibiotics and promote induced systemic resistance (ISR), which enhances nutrient uptake, stress tolerance, and disease resistance. While plant-beneficial microbes have been applied in conventional cropping systems, they have yet to be fully integrated into CEA-based systems. Oxygen availability in the root zone is critical for the functionalities of beneficial microorganisms. Insufficient levels of dissolved oxygen (DO) can hinder microbial activity, lead to the accumulation of harmful compounds, and cause stress to the plants. Contemporary aeration technologies, such as novel oxygenated nanobubble (ONB) technology, provide better oxygen distribution and promote optimal microbial proliferation, enhancing plant resilience. Hydroponic and soilless substrate-based systems of CEA production have significant potential to integrate beneficial microbes, increase crop yields, prevent diseases, and improve resource use efficiency. This review aims to summarize the significance of DO and the potential impact of novel ONB technology in CEA for managing root zone diseases while increasing crop productivity and sustainability. Full article

Background: The well-studied 18-residue-long proline-rich antimicrobial designer peptide Api137 utilizes at least two lethal intracellular mechanisms that target the bacterial 70S ribosome. First, Api137 stalls the ribosome by binding to the peptidyl-transferase center, trapping the release factor, and inhibiting protein expression. Second, Api137 disrupts the assembly of the large 50S subunit of the ribosome, resulting in partially assembled pre-50S dead-end particles that are unable to form the functional 70S ribosome. Methods: All six proline residues in Api137 were substituted with 4S- and 4R-fluoro-l-proline (Fpr), which promote the cis- and trans-conformer ratio of the preceding Xaa-Pro-bond, respectively. The effect on the antibacterial activity was studied using Escherichia coli. The underlying mechanisms were investigated by studying 70S ribosome binding, inhibition of in vitro translation, and ribosome profile analysis. Results: Interestingly, the analogs were equipotent to Api137, except for the 4S-Fpr11 and 4S-Fpr16 analogs, which were four times more or less active, respectively. The most active 4S-Fpr11 analog competed the least with Api137 for its ribosome binding site, suggesting a shifted binding site. Both Fpr14 and the 4S-Fpr16 analogs disturbed 50S subunit assembly less than Api137 or not at all. The strongest effect was observed with the 4R-Fpr16 analog resulting in the lowest 70S ribosome content and the highest pre-50S particle content. This peptide also showed the strongest competition with Api137 for its binding site. However, its antibacterial activity was similar to that of Api137, possibly due to its slower cellular uptake. Conclusions: Api137 inhibits protein translation and disrupts 50S assembly, which can be adjusted by substituting specific proline residues with fluoroproline. 4R-Fpr16 potently inhibits ribosome assembly and offers a novel, unexploited clinical mechanism for future antibiotic development. Full article

The increasing prevalence of bacterial resistance to conventional disinfectants and antibiotics has intensified the search for effective, natural alternatives in the dairy industry. This study evaluates the bactericidal efficacy of Punica granatum L. (pomegranate) peel ethanolic extract, focusing on its application in pre- and post-dipping procedures for mastitis prevention. The extract exhibited potent activity against Escherichia coli and Staphylococcus aureus, two major mastitis pathogens. At a concentration of 10 mg/mL, the extract induced significant membrane disruption within 30 s of exposure, as evidenced by propidium iodide uptake and elevated extracellular DNA levels (Escherichia coli: 64.25 ng/μL; Staphylococcus aureus: 83.25 ng/μL) compared to controls (11.20 ng/μL and 35.20 ng/μL, respectively; p < 0.05). Complete growth inhibition (100%) was achieved within 30 s at 25 and 50 mg/mL, matching the efficacy of commercial chlorhexidine and high-concentration hypochlorite. Phytochemical analysis identified punicalagin as the predominant bioactive compound. These findings establish Punica granatum peel extract as a fast-acting bactericidal agent, exhibiting an efficacy comparable to or exceeding that of conventional disinfectants. Its rapid action and plant-based origin highlight its potential as a viable alternative for the prevention and control of bovine mastitis in dairy farming. Full article

Biofilms are complex microbial communities encased within a self-produced extracellular matrix, which plays a critical role in chronic infections and antimicrobial resistance. These enhance pathogen survival and virulence by protecting against host immune defenses and conventional antimicrobial treatments, posing substantial challenges in clinical contexts such as device-associated infections and chronic wounds. Secondary metabolites derived from medicinal plants, such as alkaloids, tannins, flavonoids, phenolic acids, and essential oils, have gained attention as promising agents against biofilm formation, microbial virulence, and antibiotic resistance. These natural compounds not only limit microbial growth and biofilm development but also disrupt communication between bacteria, known as quorum sensing, which reduces their ability to cause disease. Through progress in nanotechnology, various nanocarriers such as lipid-based systems, polymeric nanoparticles, and metal nanoparticles have been developed to improve the solubility, stability, and cellular uptake of phytochemicals. In addition, the synergistic use of plant-based metabolites with conventional antibiotics or antifungal drugs has shown promise in tackling drug-resistant microorganisms and revitalizing existing drugs. This review comprehensively discusses the efficacy of pure secondary metabolites from medicinal plants, both as individuals and in nanoformulated forms or in combination with antimicrobial agents, as alternative strategies to control biofilm-forming pathogens. The molecular mechanisms underlying their antibiofilm and antivirulence activities are discussed in detail. Lastly, the current pitfalls, limitations, and emerging directions in translating these natural compounds into clinical applications are critically evaluated. Full article

Background: Influenza is an acute viral disease that primarily affects the airways. It is caused by influenza A and B—RNA viruses. The disease is associated with significant morbidity and mortality. The prevention of influenza includes chemoprophylaxis and vaccination, which are the primary preventive measures against influenza infection and should be highly considered by everyone during influenza season. Methods: A systematic literature search was performed in the databases of PubMed, Web of Science, Scopus, and Embase until September 2024. The review was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Results: Eventually, a total of 20 publications were included in the final analysis of this systematic review. While general awareness of influenza was moderate, detailed understanding of complications and vaccine safety was frequently lacking. Misconceptions—such as fears of fetal harm and confusion between antiviral and antibiotic treatments—were widespread. Vaccine uptake was generally low but strongly correlated with receiving a healthcare provider recommendation. Willingness to vaccinate was higher in settings where participants were educated during the study process, indicating a crucial role of health communication. Discussion: According to the reviewed literature, the reluctance to receive maternal vaccination often stems primarily from fears or concerns about adverse reactions or misconceptions about the vaccine’s effectiveness, as well as the absence of a physician’s recommendation. Misconceptions regarding vaccine safety, limited understanding of influenza severity, and a lack of clear communication from healthcare professionals are key contributors to low vaccination uptake. Importantly, multiple studies confirmed that recommendation by a trusted healthcare provider significantly increases vaccine acceptance. Conclusions: These findings highlight the urgent need for targeted educational strategies, improved antenatal counseling, and systems-level support to ensure that maternal influenza vaccination becomes a standard and trusted component of prenatal care worldwide. Full article

The rapid expansion of aquaculture is vital for global food security, yet it faces persistent threats from disease outbreaks, vaccine inefficacy, and antibiotic overuse, all of which undermine sustainability. Conventional vaccines often fail to induce robust mucosal immunity, spurring interest in probiotics as adjuvants to enhance immunogenicity. Probiotics such as Bacillus subtilis and Lactobacillus casei modulate fish microbiomes, fortify mucosal barriers, and activate innate immune responses via mechanisms including Toll-like receptor signaling and cytokine production. These actions prime the host environment for prolonged adaptive immunity, improving antigen uptake and pathogen clearance. Experimental advances—such as Bacillus subtilis-engineered spores increasing survival rates to 86% in Vibrio anguillarum-challenged European seabass—demonstrate the potential of this synergy. Innovations in delivery systems, including chitosan–alginate microcapsules and synbiotic formulations, further address oral vaccine degradation, enhancing practicality. Probiotics also suppress pathogens while enriching beneficial gut taxa, amplifying mucosal IgA and systemic IgM responses. However, challenges such as strain-specific variability, environmental dependencies, and unresolved ecological risks persist. Optimizing host-specific probiotics and advancing multi-omics research is critical to unlocking this synergy fully. Integrating probiotic mechanisms with vaccine design offers a pathway toward antibiotic-free aquaculture, aligning with One Health principles. Realizing this vision demands interdisciplinary collaboration to standardize protocols, validate field efficacy, and align policies with ecological sustainability. Probiotic–vaccine strategies represent not merely a scientific advance but an essential evolution for resilient, ecologically balanced aquaculture systems. Full article