Search Results (497)

The emergence of multidrug-resistant (MDR) bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA), represents a major global health challenge by limiting the current therapeutic options. In this context, antimicrobial peptides (AMPs) have been widely studied for their potent antimicrobial properties. In this study, we evaluated the anti-MRSA effect of a novel AMP, LyeTx I mnΔKL, derived from a toxin of Lycosa erythrognatha. Its activity was evaluated in vitro by minimal inhibitory and bactericidal concentrations (MIC and MBC), antibiofilm effect, membrane interaction, cytotoxicity, synergistic interaction with vancomycin, and in vivo in an MRSA murine wound/abscess infection model. LyeTx I mnΔKL showed enhanced antimicrobial activity against clinical MRSA isolates compared to its prototype (LyeTx I mnΔK), with MIC₅₀ and MBC₅₀ of 2 and 8 µM and 16 and 32 µM, respectively. Furthermore, LyeTx I mnΔKL exhibited a rapid bactericidal effect and a pronounced ability to inhibit biofilm formation and disrupt mature biofilms. LyeTx I mnΔKL interacts with bacterial membranes, adopts an α-helical structure, and induces membrane disruption and leakage of intracellular material. In vivo, topical treatment with LyeTx I mnΔKL reduced MRSA burden compared with LyeTx I mnΔK and untreated controls (log₁₀ CFU/g of wound of 2.4, 4.4, and 6.5 for LyeTx I mnΔKL, LyeTx I mnΔK, and the saline group, respectively). However, increased cytotoxicity remains a significant limitation. Overall, LyeTx I mnΔKL is a promising anti-MRSA candidate for topical use with potent antibiofilm and in vivo activity. Full article

Glycans attached to host glycoproteins play an important role in regulating oral microbial colonization and maintaining community balance. Our previous studies revealed that children exhibit lower levels of α2-3 sialylated glycan structures (SAα2-3Gal) than adults, raising the possibility that this age-associated glycan deficiency contributes to the heightened cariogenicity of Streptococcus mutans. In this study, sialylated glycoproteins (Sia-GP) and corresponding desialylated controls (DeSia-GP and α2,3-DeSia-GP) were prepared from bovine milk-derived glycoproteins to investigate the functional contribution of SAα2-3Gal. Their effects on S. mutans were evaluated by assessing bacterial growth, acid production, biofilm formation and extracellular polysaccharide synthesis, while a human oral keratinocytes (HOK cells) infection model was used to examine epithelial cell viability, wound healing, and infection-associated inflammatory responses. The results showed that Sia-GP exerted only a transient inhibitory effect on early bacterial growth without affecting final biomass, but significantly attenuated acidogenic activity, biofilm formation, and extracellular polysaccharides production in a concentration-dependent manner. These inhibitory effects were markedly attenuated following removal of α2-3-linked sialic acids, demonstrating the essential role of SAα2-3Gal. In addition, Sia-GP alleviated S. mutans-induced cellular damage in HOK cells by improving cell viability, colony formation, and migration, while suppressing infection-associated inflammatory signaling. Collectively, these findings demonstrate that SAα2-3Gal effectively limits multiple virulence traits of S. mutans and attenuates S. mutans-induced damage in oral epithelial cells. This study provides mechanistic insights into glycan-mediated regulation of host–microbe interactions and suggests that the naturally low abundance of SAα2-3Gal in children may increase their susceptibility to S. mutans infection and caries development. Full article

The escalating prevalence of bacterial infections has intensified the search for innovative antimicrobial strategies, particularly for infected wound management. Chondroitin sulfate (CS), a naturally occurring glycosaminoglycan with established biocompatibility, presents an attractive scaffold for developing metal ion-functionalized biomaterials. This study reports the fabrication of chondroitin sulfate–copper complex (CSCu) and chondroitin sulfate–zinc complex (CSZn) through an ion exchange method, wherein Cu²⁺ and Zn²⁺ ions bind to the groups of carboxylate, sulfate, or N-acetyl from the CS backbone. The resulting complexes exhibited copper or zinc loading capacities of about 6.6% and demonstrated potent antibacterial activity against E. coli and S. aureus. The integration of CSCu or CSZn with sodium alginate yielded a hydrogel system with a higher apparent viscosity, possessing injectability and spreadability on the skin surface and a porous three-dimensional internal structure conducive to wound healing applications. In a murine model of S. aureus-infected full-thickness wounds, topical application of CSCu and CSZn hydrogels substantially accelerated wound closure, achieving 97.46% and 98.11% healing, respectively, by day 10. Additionally, treatment with CSCu or CSZn hydrogels significantly attenuated systemic inflammatory responses, as reflected in lowered serum TNF-α, IL-1β, and IL-6 alongside increased IL-10. Histological evaluation confirmed enhanced re-epithelialization and stratum spinosum formation in treated wounds. These findings establish CSCu and CSZn as a promising bioactive agent for addressing bacterial wound infections through a dual mechanism of direct antibacterial action and immunomodulatory effects, offering a valuable alternative to conventional antibiotic therapies. Full article

Impaired wound healing is often caused by persistent inflammation, bacterial infection, and insufficient extracellular matrix remodeling. Natural polymer-based hydrogels represent ideal wound dressings but often struggle to balance structural stability and biological activity. Herein, we report a dual-functional network regulation strategy enabled by highly soluble mussel foot protein (HMFP) that acts simultaneously as a structural crosslinking regulator and bioactive effector to fabricate synergistic hydrogels (CS-SH-H) from β-chitosan (CS) and sodium hyaluronate (SH). HMFP homogenizes the porous microstructure, strengthens intermolecular interactions, and significantly improves thermal and structural stability via multivalent non-covalent bonding. In vitro, CS-SH-H shows excellent cytocompatibility, significantly promotes fibroblast proliferation and migration, and exerts potent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In a mouse full-thickness skin defect model, the hydrogel dramatically accelerates wound closure, reducing the residual wound area to 25% on day 7, outperforming the control groups. Immunohistochemistry confirms that HMFP suppresses TNF-α-mediated inflammation and enhances Ki-67-positive cell proliferation, leading to accelerated re-epithelialization and collagen deposition. This study establishes HMFP as a promising marine-derived dual-functional network regulator for designing high-performance hydrogel dressings. This strategy is scalable and translatable for treating infected and inflammatory wounds. Full article

Introduction: While global burden is underappreciated, traumatic wounds account for 23 million annual emergency department visits in the United States, accounting for trillions in medical costs and work and quality of life loss. We hypothesized that the use of intact fish skin grafts (IFSGs) would result in faster time to obtain a graftable wound bed compared to a synthetic matrix (SM). Methods: This retrospective analysis of patients with full-thickness acute traumatic wound was conducted on a matched sample of patients receiving IFSG versus SM. We hypothesized that there would be at least a 10-day difference between the two treatments. Two surgeons reviewed electronic charts for primary outcomes. Incomplete charts were excluded. For sensitivity analysis, both simple linear regression and generalized linear mixed models were utilized to adjust the primary outcome to potential confounders. Results: Data were reviewed for 80 patients. The final cohort included 38 patients [IFSG (n = 12) and SM (n = 26)]. Demographics were not different between groups. The mean age was 42.4 ± 20.7 years, with 62.2% being male and equal proportions having burns treated vs. another traumatic wound. The most common site was the lower extremity. All IFSG patients had negative pressure wound therapy (NPWT) placed at the time of implantation vs. 50% of SM (p = 0.001). The SM group had a larger TBSA (p < 0.001) and wound size (p = 0.001). Differences were subsequently used to adjust primary outcomes via regression. Patients with IFSG had faster time to a graftable wound bed compared to SM (mean ± SD: 13.9 ± 5.3 vs. 29.1 ± 10.3, p < 0.001). Neither wound size, burn severity, presence of infection, nor use of NPWT significantly altered the inference. Conclusions: In this paired sample, the use of IFSG as a dermal template for full-thickness traumatic injuries was associated with faster time to obtain a graftable wound bed compared to an SM. However, regression analysis alone is not enough to conclude that the same difference would exist in a prospectively controlled experiment, which should be performed. Full article

Oral infections are common health problems in companion animals, often associated with bacterial colonization, biofilm formation, and inflammation. This study investigates the efficacy of hypertonic salt tablets as an antibacterial approach and their effect on bacteria-associated inflammatory stimulation against important oral pathogens, Staphylococcus aureus and Pasteurella canis. Agar well diffusion showed that 0.3 g salt tablets exhibited antibacterial activity, with inhibition zones of 13.33 ± 0.89 mm for S. aureus and 28.75 ± 1.18 mm for P. canis, compared with 23.10 ± 0.87 mm and 31.43 ± 0.81 mm for 0.12% chlorhexidine, respectively. In vitro cytotoxicity assessment demonstrated that 1% v/v and 10% v/v released salt solutions maintained high cell viability (>80%), while morphology assays confirmed non-cytotoxicity of 1% v/v 24 h released salt solution. The 1% v/v and 10% v/v 10 min-released salt solution reduced relative biofilm formation in S. aureus to approximately 61% and 45%, respectively, and in P. canis to approximately 89% and 52%, respectively. Salt-treated bacterial suspensions induced lower NO production in RAW264.7 macrophages, decreasing NO levels from 33.17 ± 2.01 to 4.34 ± 0.65 µM for S. aureus and from 60.73 ± 0.99 to 36.33 ± 0.69 µM for P. canis, suggesting attenuation of bacteria-associated inflammatory stimulation. In a preliminary mouse oral mucosal wound model, local application of NaCl crystals for 30 min reduced total bacterial counts from 8.9 × 10² to 2.0 × 10² CFU/mL, corresponding to a 77.5% reduction. These findings suggest that hypertonic sodium chloride tablets may provide a simple localized approach for short-term reduction in oral bacterial burden and bacteria-associated inflammatory stimulation; however, further validation is required in clinically relevant oral disease models and companion animals. Full article

Infectious wounds are plagued by persistent infection, uncontrolled inflammation, and delayed repair, while traditional therapies suffer from the poor solubility of natural drugs, low bioavailability, and bacterial drug resistance. To address these issues, this study developed a photo-responsive chitosan composite hydrogel (BBR-AS@Ce6@Matrix) cross-linked by chitosan (CS) and oxidized sodium alginate (OSA), co-loaded with Berberine–Asiaticoside cocrystal (BBR-AS) and chlorin e6-loaded chitosan nanoparticles (Ce6@CS NPs). The BBR-AS co-crystal was prepared by solvent method and verified to significantly improve the solubility and dissolution of asiaticoside. The Ce6@CS NPs were fabricated via non-solvent-assisted counterion complexation, showing high encapsulation efficiency, uniform particle size, and efficient singlet oxygen generation under irradiation. The hydrogel exhibited a three-dimensional porous network, favorable rheology, high water content, pH-dependent swelling and erosion behaviors, and significantly promoted BBR/AS release in vitro. In vitro experiments demonstrated strong antibacterial activity against Escherichia coli and Staphylococcus aureus, good cytocompatibility, and enhanced migration of L929 and Hacat cells. In a rat infectious wound model, the hydrogel combined with light irradiation markedly accelerated wound closure, promoted collagen deposition and angiogenesis, upregulated VEGF/CD31, and downregulated TNF-α/IL-6. In conclusion, BBR-AS@Ce6@Matrix integrates co-crystal solubilization, nanoparticle-facilitated release, and photodynamic synergy to achieve antibacterial, anti-inflammatory, pro-angiogenic and tissue remodeling effects, providing a promising multifunctional platform for infectious wound repair. Full article

To address the challenges associated with prolonged inflammatory phases and delayed healing in clinically infected wounds, this research developed a multifunctional PB@GC@OD hydrogel integrating self-healing properties, injectability, and photothermal antibacterial efficacy. The hydrogel was constructed using oxidized dextran (OD) and glycol chitosan (GC) as the matrix, which were dynamically cross-linked via a Schiff-base reaction to form the GC@OD hydrogel. Subsequently, the photothermal agent prussian blue (PB) was incorporated to fabricate the PB@GC@OD hydrogel. The resulting PB@GC@OD hydrogel demonstrated robust self-healing capabilities and excellent injectability. Upon exposure to 808 nm near-infrared (NIR) irradiation, the hydrogel achieved efficient photothermal conversion, rapidly inducing localized hyperthermia that effectively eliminated Staphylococcus aureus, Escherichia coli, and methicillin-resistant Staphylococcus aureus (MRSA). In a mouse model of MRSA-infected wounds, the hydrogel not only maintained a moist wound microenvironment but also eradicated pathogenic bacteria via photothermal therapy, thereby significantly accelerating the healing process. Moreover, the hydrogel demonstrated favorable biocompatibility and long-term safety. Therefore, the PB@GC@OD hydrogel integrates photothermal sterilization, self-healing, injectability, hemostasis, and biocompatibility into a single platform, presenting a promising strategy for synergistic therapy and tissue regeneration in bacterially infected wounds. Full article

Background: Coronary artery disease is a leading cause of morbidity and mortality in Saudi Arabia. No national mechanism exists for standardized CABG outcome surveillance. The Saudi CABG Audit and Registry (SCAR) was established to address this gap. Methods: SCAR is a prospective multicenter clinical quality registry enrolling consecutive patients undergoing isolated or combined CABG across Saudi Arabia. The dataset captures more than 100 variables spanning demographics, comorbidities, operative details, in-hospital outcomes, and longitudinal follow-up to one year. Primary outcomes include in-hospital mortality, 30-day major adverse cardiac and cerebrovascular events (MACCE), deep sternal wound infection, and unplanned reoperation. Results: The registry incorporates structured follow-up at 30 days, 3 months, 6 months, and one year, governed through three national committees overseeing data quality and dissemination. A four-tier analytical framework progresses from descriptive analyses through risk-adjusted benchmarking, validation of international risk models, and future development of a locally derived risk prediction model. Implementation commences with a pilot phase enrolling 100–150 consecutive procedures across four centers over three months. Conclusions: SCAR represents the first dedicated national CABG registry in Saudi Arabia. Through risk-adjusted benchmarking and structured feedback, the registry may support quality improvement, multicenter research, healthcare planning, and development of locally relevant risk stratification tools. Full article

Background: Polymicrobial skin and soft tissue infections (SSTIs) are frequently complicated by methicillin-resistant Staphylococcus aureus (MRSA) and co-colonizing Gram-negative pathogens like Pseudomonas aeruginosa (P. aeruginosa). Mupirocin, the clinical gold standard, is limited by rising resistance and an intrinsic “mupirocin gap” against P. aeruginosa. This study evaluates a novel Nigella sativa (NS) seed oil topical formulation as an alternative. Methods: A 4-tier preclinical platform assessed the NS formulation against MRSA, methicillin-sensitive S. aureus (MSSA), Streptococcus pyogenes, and P. aeruginosa. The pipeline included: (1) in vitro agar diffusion, (2) a gauze biofilm prevention model, (3) an ex vivo porcine ear skin model challenging epidermal lipid barriers, and (4) an in vivo Galleria mellonella model evaluating trans-cuticular systemic protection. Results: The NS formulation produced extensive diffusion zones, completely inhibiting S. pyogenes and outperforming controls against MSSA and P. aeruginosa. In the gauze model, NS achieved complete eradication of MSSA and S. pyogenes, while significantly suppressing MRSA and P. aeruginosa biofilms (p < 0.001). In the ex vivo porcine model, NS yielded >1.5 to >2.5 log reductions across all pathogens at 24 h (p < 0.001). Furthermore, in the in vivo G. mellonella model, topical NS significantly reduced the systemic bioburden of MSSA, S. pyogenes, and P. aeruginosa (p < 0.001), though MRSA reduction lacked statistical significance. Conclusions: The novel NS formulation demonstrates potent broad-spectrum antimicrobial activity. By effectively bridging the “mupirocin gap” against P. aeruginosa and demonstrating significant efficacy against MRSA in in vitro and ex vivo environments, it represents a promising plant-based pre-clinical candidate that strongly warrants future evaluation in live mammalian wound healing models. Full article

Asthma is defined as a chronic airway inflammatory disorder with over-activation of the immune system accompanied by the inability to resolve inflammation. SPMs are novel potent lipid mediators that play an important role in maintaining inflammation homeostasis and macrophages’ functional plasticity. This review will look into the potential function of SPM-programmed macrophage reprogramming as a novel therapeutic strategy for asthma. Unlike current anti-inflammatory treatments, which only focus on suppressing inflammation, SPMs can actively drive the inflammation resolution phase by promoting efferocytosis and wound healing while maintaining the defense against infection. In experimental asthma animal models, lipoxins, resolvins, protectins, and maresins have been demonstrated to alleviate inflammation and airway hyperresponsiveness, shift macrophages towards pro-resolving phenotypes and thus facilitate the resolution process. Levels of some SPM subclasses were found to be reduced in severe or uncontrolled asthmatics, indicating defective resolution pathways may contribute to asthma persistence. The mechanisms include down-regulation of pro-inflammatory cytokines, alteration of macrophage phenotype, improvement of immune homeostasis in the airway milieu, etc. These molecules have become highly promising therapeutic agents after the development of metabolically stable analogs, receptor-targeted agonists, and an improved delivery system. Multi-omics studies coupled with patient stratification based on biomarkers will potentially help in the future to develop personalized resolution-based therapy, in particular for those steroid-resistant and non-type 2 asthmatics. Nevertheless, the evidence provided so far is mainly preclinical; more challenges in terms of pharmacokinetics, formulation and formulation development, regulatory agency approval, and clinical validation remain and will be overcome through further studies, thus warranting investigation into SPM-mediated strategies for asthma and other chronic inflammatory diseases. Full article

Background/Objectives: Foot and ankle presentations during Hajj occur in a dense mass-gathering environment where prolonged walking, heat exposure, crowding, variable footwear, and limited self-care can interact with chronic disease and wound vulnerability. Previous Hajj studies have described foot injuries and diabetes-related complications, but less is known about whether simple high-risk foot documentation flags identify presentation records with higher care-pathway intensity. The primary objective was to estimate the presentation-level burden of core high-risk foot profiles among pilgrims presenting with foot and ankle conditions during Hajj 2025. Secondary objectives were to evaluate associations with a surgery-coded care-intensity indicator, hospital referral, and component heterogeneity. Methods: This observational presentation-level analysis included 3957 foot and ankle presentation records. The unit of analysis was the presentation/case record, not a unique individual pilgrim. A core high-risk foot profile was defined as diabetes, neuropathy, diabetic foot ulcer, foot ulcer, complications of open wound, or osteomyelitis. The primary outcome was a surgery-coded care-intensity indicator, defined solely from treatment documentation containing “Surgery” and interpreted as a care-pathway proxy rather than confirmed operating-room surgery. Logistic regression estimated crude and adjusted odds ratios (ORs); exploratory risk-category analyses assessed heterogeneity within the composite profile. Results: Core high-risk foot profiles were identified in 1793/3957 presentations (45.3%). The primary outcome occurred in 239/1793 high-risk presentations (13.3%) and 201/2164 non-high-risk presentations (9.3%), an absolute difference of 4.0 percentage points. The crude OR was 1.50 (95% CI 1.23–1.83; p < 0.001). The association persisted in the primary adjusted model (adjusted OR 1.47; 95% CI 1.20–1.79; p < 0.001) and in the extended clinical sensitivity model (adjusted OR 1.47; 95% CI 1.20–1.80; p < 0.001). Care pathways and secondary outcomes are summarized was also more frequent in high-risk presentations (12.2% vs. 9.8%; crude OR 1.28; 95% CI 1.05–1.57; p = 0.017). Exploratory category analysis showed that chronic-risk-only presentations had a primary outcome rate similar to non-high-risk presentations (9.0% vs. 9.3%), whereas ulcer/wound/deep-infection presentations had a higher rate (17.3%; crude OR 2.04; 95% CI 1.63–2.55; p < 0.001). Model discrimination was modest (C-statistics 0.55–0.64). Conclusions: Core high-risk foot flags were common among Hajj foot and ankle presentation records and were associated with surgery-coded care-intensity and referral documentation. However, the composite was clinically heterogeneous, the outcome was not a validated surgery endpoint, and the models were not prediction tools. These findings support cautious use of high-risk foot flags as operational prompts for assessment and pathway planning rather than as standalone clinical risk estimates. Full article

Impaired wound healing arises from interacting biological and material challenges, including persistent infection, biofilm formation, oxidative stress, unresolved inflammation, impaired angiogenesis, defective epithelialization, hemorrhage, and insufficient real-time assessment of wound status. Quantum dot (QD) and nanodot nanosystems have emerged as a versatile class of bioactive wound interfaces capable of addressing these barriers through functions that extend beyond passive coverage. This review synthesizes the design rationale, material composition, validation strategies, functional outcomes, mechanistic interpretation, and translational relevance of QD-enabled platforms for precision wound repair. Across the reviewed literature, carbon dots, graphene QDs, black phosphorus QDs, metal and metal oxide QDs, transition-metal nanodots, and hybrid nanocomposites were incorporated into hydrogels, films, sponges, nanofibers, microneedles, scaffolds, membranes, sprays, and injectable matrices. Their major precision-enabling attributes include localized antimicrobial and antibiofilm activity, redox-adaptive behavior, photothermal and photodynamic activation, inflammatory and macrophage modulation, hemostasis, controlled therapeutic delivery, angiogenic and epithelial support, and fluorescence-based monitoring. The strongest conceptual advance is the transition from static wound dressings toward adaptive biointerfaces that can sense, respond to, or compensate for local wound state abnormalities. Nevertheless, the field remains largely preclinical, with important gaps in long-term safety, standardized characterization, clinically predictive models, manufacturing reproducibility, regulatory alignment, and human validation. Future progress will depend on rationally simplified multifunctional platforms, rigorous comparative testing, wound state-specific evaluation frameworks, and translation-oriented safety and usability studies. QD nanosystems therefore represent a promising foundation for precision wound repair, provided that their multifunctionality is matched by equally rigorous evidence of safety, reproducibility, and clinical relevance. Full article

Diabetic chronic wounds are often accompanied by excessive wound exudate maceration, which prolongs the inflammatory phase and increases the risk of infection. Such a complex wound microenvironment imposes more stringent requirements on multifunctional wound dressings. A multifunctional Cur Janus nanofibrous dressing is developed by integrating an electrospun poly(ε-caprolactone)/gelatin hydrophilic layer with a curcumin (Cur)-loaded PCL hydrophobic layer. Janus structure with asymmetric wettability, which exhibited unidirectional liquid transport properties both in vitro and in vivo. Its unique structure also makes it possible to carry both hydrophilic and hydrophobic drugs at the same time. The incorporation of curcumin endows the dressing with antibacterial and antioxidant functionalities, offering the potential to modulate the inflammatory microenvironment of diabetic chronic wounds. Furthermore, the wound healing ability and anti-inflammatory effects of Cur Janus nanofibers were evaluated in a diabetic mouse model. The results showed that Cur Janus nanofibers significantly reduced wound area, increased the proportion of pro-healing M2 macrophages, shortened the inflammatory phase, and ultimately accelerated diabetic wound healing. This work provides a multifunctional and scalable platform for advanced wound dressing design. Its excellent antibacterial, antioxidant (ROS scavenging) and anti-inflammatory (macrophage phenotype M1 to M2) properties, combined with the unidirectional fluid transport and dual-release potential of hydrophilic and hydrophobic drugs, demonstrate broad prospects in the management of diabetic wounds. Full article

Wound infections due to antibiotic resistance pose a global public health problem. Phage therapy is a promising approach to address this issue. To improve localization, phage stability, delivery, and antibacterial performance, we propose polymer mix gel microbeads encapsulated with phages as a model for the delivery of phiKZ bacteriophage to combat Pseudomonas aeruginosa. Phages were loaded into the alginate pre-gel under magnetic stirring, with further cross-linking by chitosan and/or Ca²⁺ ions. The obtained gel microbeads were characterized using FTIR and Raman spectroscopy, and their cytotoxicity and antimicrobial properties were evaluated. This study demonstrated the efficient loading of high-titer phage lysate, achieving up to 99% encapsulation efficiency for alginate–chitosan microbeads. The key characteristics of the microbeads include stable physicochemical properties, slow but continuous phage release over 48 h in physiological saline, and low cytotoxicity. The phage-loaded microbeads demonstrated strong in vitro antimicrobial activity against P. aeruginosa PAO1, resulting in mean reductions of 6.9 log₁₀ and 4.8 log₁₀ CFU/mL for alginate and alginate–chitosan formulations, respectively. This corresponded to a decrease in bacterial concentration from approximately 1.1 × 10¹¹ CFU/mL in untreated controls to 1.1 × 10⁵ CFU/mL and 7.7 × 10⁶ CFU/mL for alginate and alginate–chitosan formulations after 3 h of incubation. Full article