Search Results (19,938)

As global demand grows for natural health-promoting food ingredients, the agri-food industry’s organic wastes are emerging as promising alternatives thanks to attributes such as biocompatibility, nutritional value and nutraceutical effect. During saffron (Crocus sativus L.) production, approximately 53 kg of petals are obtained as a by-product for every 1 kg of saffron spice. The use of saffron petals and petal extracts in bakery products improves products’ shelf life due to the petals’ high content of nutraceuticals and minerals acting as natural preservatives. Petal-enriched bakery products contain high levels of fiber, minerals and antioxidants. Addition of saffron petals into bread dough reduces gluten network strength, increases crumb hardness, enhances acidity, improves water retention, alters color profiles and increases the duration of the shelf life. The formulation for incorporating saffron petals or petal extracts into food products must address three primary criteria: the maximum concentration of bioactive compounds per 100 g of the finished matrix, the thermal stability of these compounds during the baking process, and their bioavailability (in the food matrix) within the human gastrointestinal tract. Nutraceuticals with pharmacological potential are also influenced by the compositional profile: the proximate composition, minerals, phenolic content, flavonols, and antioxidant capacity of saffron petals and bakery products containing saffron petals. Saffron petals exhibit diverse therapeutic potentials, acting as antidepressants, anxiolytics, anticonvulsants, and neuroprotective agents. They also offer metabolic, cardiovascular, hepatoprotective, and renoprotective benefits, along with anti-inflammatory, antimicrobial, and antitumor activities. This article proposes a roadmap for developing bakery products enriched with saffron petals or petal extracts, targeting both pharmacological applications and consumer goods focused on disease prevention and general wellness. This study investigates the biochemical composition of saffron petals and their integration into bakery products. It evaluates the influence of petal-derived additives on rheological properties, shelf stability, and organoleptic characteristics, alongside an assessment of their bioactivity and toxicological profiles. Furthermore, the analytical methodologies employed for ingredient and biological sample characterization are discussed, emphasizing their role in verifying the authenticity, safety, and nutritional functionality of both raw materials and finished formulations. Full article

Gut microbiota play crucial roles in host health, including immune regulation, metabolism, and nutrient absorption. Its dysregulation has been linked to various diseases. When administered in sufficient amounts, probiotics can contribute to restoring the gut microbial balance and maintain homeostasis. Species of the genus Bacillus and related genera (Alkalihalobacillus and Heyndrickxia) have been extensively studied and commercialized as probiotics due to their ability to form endospores, the dormant cell forms that provide remarkable resistance to adverse conditions. Understanding the mechanisms of the action of spore-forming probiotics is essential for harnessing their therapeutic potential. This review explores the mechanisms underlying the action of spore-forming probiotics, with a special focus on Alkalihalobacillus clausii. Many beneficial properties such as resilience in extreme conditions, multiplication in the gut, gut adhesion, immunomodulatory effects, the production of bioactive and antimicrobial compounds, as well as efficacy in human health and diseases are extensively dissected. In parallel, this review underscores the limitations of spore-forming probiotics, focusing on safety concerns, issues related to dose standardization and quality control, as well as potential off-target effects and risks in immunocompromised individuals. Full article

The rise in antimicrobial resistance represents a significant challenge to global health. The reason partially lies in an inappropriate use of conventional antibiotics and the subsequent rapid spread of multidrug-resistant pathogen strains. This emergency requires an urgent search for conceptually new antimicrobial agents. A viable alternative to conventional antibiotics is antimicrobial peptides (AMPs), which are ribosomally synthesized molecules with considerable potential as next-generation anti-infectious therapeutics. Previously, we have reported on the β-hairpin peptide Ap9, an analog of abarenicin from the marine polychaeta Abarenicola pacifica, with potent activity against key Gram-negative pathogens. Here, it is shown that Ap9 acts in a manner resembling polymyxin B, namely via interaction with lipopolysaccharide (LPS), and retains its activity against polymyxin-resistant isolates without observed cross-resistance, and causes insignificant damage in cytoplasmic membrane at bactericidal concentrations. NMR spectroscopy reveals that LPS binding induces a conformational rearrangement of Ap9, its dimer formation, and local structural remodeling of the peptide region (residues 8–12) into 3₁₀-helix. Bacterial resistance to Ap9 was found to be relatively low with a reduced susceptibility associated with infrequent genetic alterations, such as the mutation in lptD or the deletion in mlaA. Furthermore, Ap9 demonstrates a favorable tolerability, a wider therapeutic window than that of polymyxin B, and a sufficiently long half-life through the systemic use, as well as in vivo efficacy in murine models of Gram-negative infections, including sepsis caused by the mcr-1-harboring Escherichia coli strain. The obtained results point to Ap9 as a promising candidate for further preclinical studies aimed at development of an alternative to polymyxins. Full article

Quorum Quenching (QQ) is a mechanism that disrupts Quorum Sensing (QS) signaling systems, which regulate gene expression based on bacterial population density. Many fish pathogens, such as Aeromonas, utilize QS systems to regulate the expression of their virulence factors. Disrupting these systems using QQ is a promising approach for infection control in aquaculture and may provide a safe alternative to antibiotics. Therefore, identifying microorganisms with QQ activity is a relevant task in agricultural microbiology and veterinary medicine. This study examines the identification of isolates with QQ activity in the microbial community of perch and assesses their probiotic potential for the prevention of aeromonosis. In this study, we isolated 32 strains of microorganisms capable of degrading N-acylhomoserine lactone (AHL), six of which exhibited stable QQ activity. Five strains were found to belong to the genus Rhodococcus, and one strain to the genus Exiguobacterium. The selected strains were tested for the enzymatic/non-enzymatic and intra-/extracellular QQ activity, pathogen growth inhibition, biofilm formation, and hemolytic activity, as well as growth ability under various environmental conditions (salinity, pH, bile acids, and temperature). Based on the results of these tests, the R. erythropolis PFS1.20 strain was selected as the most promising probiotic. The genomic analysis revealed that the studied strain contains genes encoding QQ enzymes, siderophore biosynthesis clusters, osmoprotectors, and compounds with antimicrobial properties. These results indicate the high probiotic potential of the R. erythropolis PFS1.20. Full article

Neutrophils are the most abundant circulating leukocytes and are characterized by a proteome in which granule-associated proteins synthesized during granulopoiesis constitute a major fraction of total cellular protein, reflecting their preloaded effector nature in innate immune defense. A striking feature of neutrophil biology is the unusual abundance of the calcium-binding proteins S100A8 and S100A9, which together form the heterodimeric complex known as calprotectin. Early biochemical studies estimated that S100A8/A9 constitutes a substantial fraction of the soluble cytosolic proteome in neutrophils, with later studies often describing it as one of the most abundant protein complexes in these cells. Despite extensive studies on the antimicrobial and inflammatory activities of calprotectin, the biological rationale for this unusual abundance remains incompletely understood. In this review, we examine the structural, biochemical, and regulatory features of S100A8/A9 and explore the potential explanations for its high abundance in the neutrophil cytosol. We first discuss the unique organization of the neutrophil proteome and the transcriptional programs governing granulopoiesis that lead to large-scale production of neutrophil effector proteins. We then review the structural and biochemical properties of S100A8/A9, including its calcium-dependent conformational dynamics and high-affinity transition metal binding, which contribute to antimicrobial defense through nutritional immunity. Several functional hypotheses are considered to explain calprotectin abundance, including roles as an antimicrobial reservoir, a metal-sequestering molecule, a regulator of oxidative stress, and a source of damage-associated molecular patterns. Finally, we discuss the evolutionary logic of neutrophil protein preloading and the implications of calprotectin biology in inflammatory diseases and the tumor microenvironment. Resolving the abundance paradox of S100A8/A9 may reveal fundamental principles governing the organization of innate immune cell proteomes and provide new insights into the strategies used by neutrophils to achieve rapid and effective host defense. Full article

Mesenchymal stem/stromal cells (MSCs) are widely recognized as potent modulators of inflammation and immune function in bacterial and viral infections. However, their roles in fungal disease remain comparatively under-defined despite the growing clinical burden of invasive and opportunistic mycoses. This Feature Review synthesizes emerging evidence that MSCs influence antifungal outcomes through two complementary axes: (i) host-directed effects, including modulation of immune responses, particularly macrophage responses, and tissue/barrier conditioning; and (ii) fungus-directed effects (direct antifungal activity mediated by contact-dependent mechanisms and secreted antimicrobial factors). We will summarize how MSCs reshape cytokine and chemokine networks and tune innate immune effector functions, with emphasis on macrophage polarization, pattern-recognition receptor signaling, and downstream phagocytic and fungicidal pathways. In parallel, we will review data suggesting that MSCs can interact more directly with fungal pathogens through sensing, physical engagement, and secretion of antimicrobial mediators while highlighting mechanistic uncertainties and model-dependent limitations. A dedicated section will address MSC-derived secretome products (conditioned media, extracellular vesicles) as a cell-free strategy to enhance antifungal immunity. We will critically evaluate conflicting findings across studies, highlighting that outcomes depend on pathogen and host context. Clarifying these context dependencies is essential to rationally develop MSC or secretome-based interventions that are safe, reproducible, and tailored to specific fungal pathogens and patient populations. Full article

Background/Objectives: The rapid emergence of antimicrobial resistance (AMR) is driven not only by antibiotic selective pressure but also by bacterial adaptive responses that enhance genetic diversification under stress. The SOS response, regulated by the RecA-LexA axis, plays a central role in coordinating DNA repair, mutagenesis, and phenotypic adaptation. Targeting this pathway represents a promising strategy to limit bacterial adaptability without directly affecting viability. This study aimed to evaluate benzoxaborole-based compounds as potential inhibitors of the LexA regulatory pathway. Methods: A drug repurposing approach was employed to investigate the benzoxaborole scaffold and the clinically approved derivatives tavaborole and crisaborole. Biochemical assays were used to assess LexA autocleavage in a RecA-dependent co-protease system. Molecular docking analyses were performed to evaluate compound binding within the LexA catalytic site. Microbiological assays were conducted to examine the effects on antibiotic-induced filamentation and biofilm formation under different growth conditions. Results: Selected benzoxaboroles inhibited LexA autocleavage, with tavaborole showing the strongest inhibitory profile in the biochemical assay. Docking analyses supported these findings, indicating stable binding within the LexA catalytic site near the catalytic serine residue. At the cellular level, tavaborole and benzoxaborole significantly reduced levofloxacin-induced filamentation at sub-inhibitory concentrations. Both compounds also decreased biofilm formation under nutrient-limited conditions, while no significant effects were observed on preformed biofilms. Crisaborole showed limited cellular activity despite measurable biochemical effects. Conclusions: These findings identify benzoxaboroles as modulators of the LexA-dependent SOS response and support the potential repurposing of clinically approved compounds as adjuvants to limit bacterial adaptive responses associated with antimicrobial resistance. Full article

Anti-inflammatory agents, antipyretics, and antibiotics are commonly used to manage fever and pain associated with infectious diseases in both adults and children. Despite their effectiveness, inappropriate and unnecessary prescriptions remain widespread, leading to adverse patient outcomes and, in the case of antibiotics, contributing to antimicrobial resistance. Addressing these issues requires effective stewardship programs focused on educating healthcare professionals and the public on evidence-based guidelines for optimal prescribing practices. This paper explores the five “A”s fundamental to infection management in pediatric and adult patients: appropriateness, abuse, antipyretics, anti-inflammatory agents, and antibiotics. Through a comprehensive literature review, expert perspectives, and clinical guidelines, the study evaluates the roles of anti-inflammatory agents (e.g., ibuprofen), antipyretics (e.g., paracetamol), and antibiotics in clinical practice, highlighting best practices for their use. Current guidelines emphasize that antipyretics should only be administered when fever is accompanied by significant discomfort or pain, as fever itself plays a role in the immune response. Based on the available literature, experts also suggest that paracetamol should be preferred as a first-line antipyretic due to its favorable safety profile, while ibuprofen should be used with caution, particularly during respiratory infections, varicella, and severe bacterial infections, due to its potential to exacerbate complications. According to experts, special consideration is also required for patients with renal or gastrointestinal comorbidities to prevent toxicity. Regarding antibiotics, prescriptions should be limited to clear evidence of bacterial infection to avoid unnecessary patient exposure and the development of antimicrobial resistance. Stewardship programs underscore the importance of selecting the right agent, optimizing dosing, and introducing shorter treatment regimens where supported by evidence, to improve therapeutic outcomes while minimizing resistance risks. Ultimately, this paper provides practical, evidence-based recommendations to support rational prescribing of antipyretics, anti-inflammatory drugs, and antibiotics, aiming to optimize patient outcomes, prevent unnecessary toxicity, and contribute to global efforts against antimicrobial resistance. Full article

Fermented dairy products with probiotic and functional properties are a promising matrix for modulation of the human microbiome. The functionality of such products will depend not only on the technological properties of the lactic acid bacteria included in the starter culture but also on the combined effects of metabolites, enzymatic activity, stress tolerance, and strain-specific adaptation mechanisms. The aim of this work was to conduct a comprehensive analysis of Lactobacillus strains to facilitate the design of microbial consortia for the development of fermented products with diverse functional properties. Twenty Lactobacillus strains from different species were investigated using microbiological, physicochemical, and biochemical methods to evaluate antagonistic activity against opportunistic microorganisms and to assess changes in amino acid and organic acid profiles, vitamin content, fatty acid composition, and enzymatic activity. Additionally, proteomic analysis was performed to create a matrix of functional complementarity of the studied strains, representing proteins associated with antimicrobial activity, bacteriocin transport, resistance to oxidative stress, surface structure formation, and adhesion. It was shown that the studied strains exhibit pronounced functional heterogeneity, demonstrating the feasibility of scientifically based selection of strains to create next-generation fermented dairy products with predictable properties. Full article

Background: Sulfated chitosan (ChS) is a chemically modified polysaccharide derived from chitin that mimics heparan sulfate (HS) structures and has emerged as a promising antimicrobial biomaterial. Piscirickettsia salmonis, the etiological agent of Salmonid Rickettsial Septicemia (SRS), represents the main driver of antibiotic use in Chilean aquaculture. Objective: In this study, the in vitro antibacterial activity of ChS against P. salmonis was evaluated. Methods: Elemental characterization by SEM-EDS and FTIR analysis confirmed successful sulfation of the polymer, with a degree of sulfation ranging from 0.92 to 0.95. Additionally, X-ray diffraction (XRD) analysis revealed a reduction in polymer crystallinity, indicating a transition toward a more amorphous structure associated with increased molecular flexibility and functional group accessibility. Results: Antibacterial assays revealed a minimum inhibitory concentration (MIC) of 1500 µg/mL and a minimum bactericidal concentration (MBC ≥ 1500 µg/mL). LIVE/DEAD™ fluorescence imaging showed the formation of bacterial aggregates with increasing size, frequency, and red fluorescence compared to controls over the exposure to ChS, indicating progressive membrane damage. This was supported by a reduction (p < 0.05) in the Green/Red fluorescence ratio of 37–46% between 5 h and 96 h of exposure, corresponding to alteration of the cell membrane. Scanning electron microscopy revealed pronounced morphological alterations by ChS, including surface disruption and loss of cellular integrity. This was more severe compared to commercial chitosan (ChC). Also, ChS reduced (p < 0.05) biofilm formation (>50% at day 6 and 34.8% at day 8). Conclusions: These results demonstrated that ChS disrupts the cell membrane and reduces biofilm formation in P. salmonis, thereby affecting viability. This is the first report of the antibacterial effect of ChS, an HS analogue, against P. salmonis. Full article

Fungi represent a prolific source of structurally diverse secondary metabolites, yet the extent to which culture conditions reshape the metabolic profile and functional bioactivity remains incompletely understood. In this exploratory study, ten fungal strains belonging to genera Penicillium and Aspergillus were cultivated in Yeast Extract Sucrose (YES) and Czapek Yeast Autolysate (CYA) media and analysed using untargeted LC-HRMS metabolomics. The objective of this study was to evaluate how culture medium influences metabolic profiles and to investigate medium-dependent metabolic variation and its relation to cytotoxic, antibacterial, and antifungal activities. Global metabolic profiling revealed moderate but statistically significant medium-associated metabolite variation, with discriminant metabolites predominantly enriched under CYA conditions. Putative structural annotation suggested patterns consistent with differential regulation of isoprenoid-derived sterols, terpenoids, alkaloid-like metabolites, and aromatic polyketides. While antimicrobial activities displayed a heterogeneous, strain-dependent pattern with limited correlation to individual metabolites, cytotoxic activity co-varied with metabolite composition in OPLS regression modelling. Sterols and terpenoid-related features emerged as major contributors to cytotoxicity. Given the absence of biological replication and the limited sample size inherent to this pilot study, all findings should be considered hypothesis-generating and interpreted within an exploratory framework. These results suggest that nutrient composition influences biosynthetic pathway activation while functional outcomes remain strongly dependent on strain-specific metabolic capacity. This work provides a systematic framework and targeted hypothesis for future investigations into condition-dependent fungal chemical diversity in natural product discovery. Full article

Background/Objectives: Multidrug-resistant (MDR) Gram-negative bacteria represent a significant public health concern worldwide, particularly in resource-limited settings. In Ghana’s Tamale Metropolis, limited data exist on the prevalence and trends of MDR bacteria, posing challenges to effective antimicrobial stewardship. Methods: This study analyzed microbiological data from 2020 to 2023 to address these knowledge gaps. Results: Among the 4859 clinical samples analyzed, 1570 (33.7%) yielded Gram-negative bacterial isolates, with an MDR prevalence of 40.6%. The most frequently isolated organisms were Klebsiella spp. (28.9%) and Escherichia coli (20.4%). Resistance to cephalosporins (51%) and ciprofloxacin (46%) was particularly pronounced, highlighting the diminishing efficacy of commonly used antibiotics. Older adults (aged 60 years and above) presented the highest MDR prevalence, reflecting the vulnerability of this demographic group. Conclusion:These findings underscore the urgent need for enhanced antimicrobial stewardship programs, improved infection prevention and control measures, and continuous resistance monitoring to combat the growing threat of MDR bacteria in the region. Strengthening laboratory capacity and adherence to strict antibiotic usage policies are crucial for reducing the burden of MDR infections and improving patient outcomes. Full article

Staphylococcus pseudintermedius is an opportunistic bacterium previously associated with dogs but has recently been found in human infections, raising zoonotic concerns. Genomic characterization of human S. pseudintermedius isolates can provide preliminary information on antibiotic resistance, pathogenicity, and genomic features relevant to host range. Two S. pseudintermedius isolates (hereafter referred to as S. pseudintermedius EGH1 and S. pseudintermedius EGH2) from human clinical samples in Egypt were sequenced using the Illumina NovaSeq X Plus platform. To assess genetic relatedness to human S. pseudintermedius isolates worldwide, multilocus sequence typing (MLST), pangenome analysis, and antimicrobial resistance gene profiling were performed. The sequencing produced a total of 9,499,989 reads for S. pseudintermedius EGH1 and 9,567,531 reads for S. pseudintermedius EGH2. Sequences were assembled with Geneious Prime^® 2025 and annotated using NCBI Prokaryotic Genome Annotation Pipeline v6.10. Pangenome analysis identified 9574 genes, comprising 1681 core genes (17.56%), 180 soft-core genes (1.88%), 837 shell genes (8.74%), and 6876 cloud genes (71.82%). MLST was conducted on human S. pseudintermedius genome assemblies using MLST v2.23.0. The analysis revealed both isolates as novel sequence types: S. pseudintermedius EGH1 was assigned ST-3037 with a new allele (purA-107), and S. pseudintermedius EGH2 was assigned ST-2874. Clonal relationships among S. pseudintermedius isolates were evaluated using the eBURST algorithm. This study presents the first next-generation genome sequencing and comparative genomic analysis of S. pseudintermedius isolates from humans in Egypt. Future studies integrating genomic, epidemiological, and phenotypic data are required. Full article

Background: Driveline infection (DLI) is the most common device-specific infection in patients supported with ventricular assist devices (VADs) and remains a major cause of morbidity during long-term mechanical circulatory support. This study aimed to evaluate the incidence, risk factors, microbiological characteristics, and antimicrobial resistance patterns of DLIs in patients undergoing durable left ventricular assist device (LVAD) implantation. Methods: This retrospective cohort study included 772 consecutive patients who underwent durable LVAD implantation at a single tertiary center between January 2012 and December 2024. Patients were categorized according to the development of DLI: the DLI group (n = 158) and the non-DLI group (n = 614). Demographic, clinical, laboratory, perioperative, and postoperative variables were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of DLI. Microbiological isolates and antimicrobial resistance patterns were also evaluated. Results: Driveline infection developed in 20.5% of patients during follow-up. Patients with DLI had a significantly higher body mass index (26.4 vs. 24.8 kg/m², p = 0.002) and a higher prevalence of diabetes mellitus (28.2% vs. 12.1%, p < 0.001). In multivariate analysis, diabetes mellitus (OR 3.29, p = 0.013) and longer LVAD support duration (p = 0.003) were independently associated with DLI. Device type showed differences in crude infection rates but was not an independent predictor. The most frequently isolated pathogens were Staphylococcus aureus (36%) and Pseudomonas aeruginosa (19%). The most common antimicrobial resistance patterns included fluoroquinolone resistance (23%), methicillin-resistant Staphylococcus aureus (10%), and resistance to piperacillin/tazobactam and carbapenems. Conclusions: In this large single-center cohort, diabetes mellitus and prolonged device support duration were the main independent predictors of driveline infection. Staphylococcus aureus and Pseudomonas aeruginosa were the predominant pathogens, with notable antimicrobial resistance patterns. These findings highlight the importance of metabolic optimization, meticulous driveline exit-site care, and structured long-term surveillance strategies for reducing infection risk in LVAD recipients. Full article

Background/Objectives: Lyme disease is a tick-borne zoonosis caused by Borrelia burgdorferi that can affect multiple organ systems. Although cardiovascular involvement is considered uncommon, it may lead to severe and potentially life-threatening complications, particularly conduction disturbances and inflammatory cardiac conditions. This review aims to describe the spectrum of cardiovascular manifestations documented in patients with Lyme disease, focusing on clinical presentation, diagnostic approaches, management strategies, and reported outcomes. Methods: A narrative literature review was performed using PubMed, MEDLINE, and Google Scholar. Articles published between January 2000 and July 2025 in English or Spanish were screened. Eligible studies included original research articles, systematic and narrative reviews, case series, and case reports describing confirmed Lyme disease with cardiovascular involvement. A total of 30 studies were included. The available evidence was predominantly based on case reports and small case series, with considerable heterogeneity in study design, patient populations, and reported outcomes. Data on clinical manifestations, diagnostic methods, treatment strategies, and outcomes were extracted and synthesized. Results: Atrioventricular conduction disturbances were the most frequently reported cardiovascular manifestation, ranging from first-degree block to complete heart block, often presenting abruptly with syncope or bradycardia. Other reported manifestations included atrial and ventricular arrhythmias, myocarditis, pericarditis, myopericarditis, valvular endocarditis, aortitis, and vasculitis. Diagnosis relied on a combination of clinical suspicion, epidemiologic exposure, serologic testing, electrocardiographic monitoring, and cardiac imaging. Most patients were treated with antimicrobial therapy, commonly intravenous ceftriaxone followed by oral doxycycline, with temporary pacemaker support required in selected cases. Overall, clinical outcomes were favorable when treatment was initiated promptly. Conclusions: Cardiovascular involvement in Lyme disease, although infrequent, encompasses a broad clinical spectrum with potentially serious consequences. Early recognition, appropriate diagnostic evaluation, and timely antimicrobial therapy are essential to ensure reversibility of cardiac manifestations and favorable outcomes. However, the available evidence is limited by heterogeneity and the predominance of low-level-evidence studies. Full article