RESUMEN
BACKGROUND: Plasmodium falciparum, the malaria-causing parasite, is a leading cause of infection-induced deaths worldwide. The preferred treatment approach is artemisinin-based combination therapy, which couples fast-acting artemisinin derivatives with longer-acting drugs, such as lumefantrine, mefloquine, and amodiaquine. However, the urgency for new treatments has risen due to the parasite's growing resistance to existing therapies. In this study, a common characteristic of the P. falciparum proteome-stretches of poly-lysine residues, such as those found in proteins related to adhesion and pathogenicity-is investigated for its potential to treat infected erythrocytes. METHODS: This study utilizes in vitro culturing of intra-erythrocytic P. falciparum to assess the ability of poly-lysine peptides to inhibit the parasite's growth, measured via flow cytometry of acridine orange-stained infected erythrocytes. The inhibitory effect of many poly-lysine lengths and modifications were tested this way. Affinity pull-downs and mass spectrometry were performed to identify the proteins interacting with these poly-lysines. RESULTS: A single dose of these poly-basic peptides can successfully diminish parasitemia in human erythrocytes in vitro with minimal toxicity. The effectiveness of the treatment correlates with the length of the poly-lysine peptide, with 30 lysine peptides supporting the eradication of erythrocytic parasites within 72 h. PEG-ylation of the poly-lysine peptides or utilizing poly-lysine dendrimers and polymers retains or increases parasite clearance efficiency and bolsters the stability of these potential new therapeutics. Lastly, affinity pull-downs and mass-spectrometry identify P. falciparum's outer membrane proteins as likely targets for polybasic peptide medications. CONCLUSION: Since poly-lysine dendrimers are already FDA-approved for drug delivery and this study displays their potency against intraerythrocytic P. falciparum, their adaptation as anti-malarial drugs presents a promising new therapeutic strategy for malaria.
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Antimaláricos , Eritrocitos , Plasmodium falciparum , Plasmodium falciparum/efectos de los fármacos , Antimaláricos/farmacología , Antimaláricos/química , Eritrocitos/efectos de los fármacos , Eritrocitos/parasitología , Péptidos/farmacología , Péptidos/química , Humanos , Polímeros/farmacología , Polímeros/química , Polilisina/farmacología , Polilisina/químicaRESUMEN
Human norovirus (HuNoV) is an enteric infectious pathogen belonging to the Caliciviridae family that causes occasional epidemics. Circulating alcohol-tolerant viral particles that are readily transmitted via food-borne routes significantly contribute to the global burden of HuNoV-induced gastroenteritis. Moreover, contact with enzymes secreted by other microorganisms in the environment can impact the infectivity of viruses. Hence, understanding the circulation dynamics of Caliciviridae is critical to mitigating epidemics. Accordingly, in this study, we screened whether environmentally abundant secretase components, particularly proteases, affect Caliciviridae infectivity. Results showed that combining Bacillaceae serine proteases with epsilon-poly-L-lysine (EPL) produced by Streptomyces-a natural antimicrobial-elicited anti-Caliciviridae properties, including against the epidemic HuNoV GII.4_Sydney_2012 strain. In vitro and in vivo biochemical and virological analyses revealed that EPL has two unique synergistic viral inactivation functions. First, it maintains an optimal pH to promote viral surface conformational changes to the protease-sensitive structure. Subsequently, it inhibits viral RNA genome release via partial protease digestion at the P2 and S domains in the VP1 capsid. This study provides new insights regarding the high-dimensional environmental interactions between bacteria and Caliciviridae, while promoting the development of protease-based anti-viral disinfectants.
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Bacillaceae , Polilisina , Serina Proteasas , Streptomyces , Streptomyces/enzimología , Polilisina/farmacología , Polilisina/química , Polilisina/metabolismo , Serina Proteasas/metabolismo , Bacillaceae/enzimología , ARN Viral/genética , ARN Viral/metabolismo , Humanos , Genoma Viral , Animales , Norovirus/efectos de los fármacos , Norovirus/genética , Inactivación de Virus/efectos de los fármacos , Caliciviridae/genética , Antivirales/farmacologíaRESUMEN
AIMS: This study evaluates the antibacterial characteristics and mechanisms of combined tea polyphenols (TPs), Nisin, and ε-polylysine (PL) against Streptococcus canis, Streptococcus minor, Streptococcus mutans, and Actinomyces oris, common zoonotic pathogens in companion animals. METHODS AND RESULTS: Pathogenic strains were isolated from feline oral cavities and assessed using minimum inhibitory concentration (MIC) tests, inhibition zone assays, growth kinetics, and biofilm inhibition studies. Among single agents, PL exhibited the lowest MIC values against all four pathogens. TP showed significant resistance against S. minor, and Nisin against S. mutans. The combination treatment (Comb) of TP, Nisin, and PL in a ratio of 13:5:1 demonstrated broad-spectrum antibacterial activity, maintaining low MIC values, forming large inhibition zones, prolonging the bacterial lag phase, reducing growth rates, and inhibiting biofilm formation. RNA sequencing and metabolomic analysis indicated that TP, Nisin, and PL inhibited various membrane-bound carbohydrate-specific transferases through the phosphoenolpyruvate-dependent phosphotransferase system in S. canis, disrupting carbohydrate uptake. They also downregulated glycolysis and the citric acid cycle, inhibiting cellular energy metabolism. Additionally, they modulated the activities of peptidoglycan glycosyltransferases and d-alanyl-d-alanine carboxypeptidase, interfering with peptidoglycan cross-linking and bacterial cell wall stability. CONCLUSIONS: The Comb therapy significantly enhances antibacterial efficacy by targeting multiple bacterial pathways, offering potential applications in food and pharmaceutical antimicrobials.
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Antibacterianos , Biopelículas , Pruebas de Sensibilidad Microbiana , Nisina , Polilisina , Polifenoles , Té , Animales , Nisina/farmacología , Antibacterianos/farmacología , Polilisina/farmacología , Polifenoles/farmacología , Gatos , Té/química , Biopelículas/efectos de los fármacos , Streptococcus/efectos de los fármacos , Streptococcus/genética , Transcriptoma , Boca/microbiología , MetabolómicaRESUMEN
Myocardial infarction (MI) is a serious cardiovascular disease with complex complications and high lethality. Currently, exosome (Exo) therapy has emerged as a promising treatment of ischemic MI due to its antioxidant, anti-inflammatory, and vascular abilities. However, traditional Exo delivery lacks spatiotemporal precision and targeting of microenvironment modulation, making it difficult to localize the lesion site for sustained effects. In this study, an injectable oxidized hyaluronic acid-polylysine (OHA-PL) hydrogel was developed to conveniently load adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) and improve their retention under physiological conditions. The OHA-PL@Exo hydrogel with high spatiotemporal precision is transplanted minimally invasively into the ischemic myocardium to scavenge intracellular and extracellular reactive oxygen species, regulate macrophage polarization, and attenuate inflammation in the early phase of MI. In addition, this synergistic microenvironment modulation can effectively reduce myocardial fibrosis and ventricular remodeling, promote angiogenesis, and restore electrophysiological function in the late stage of MI. Therefore, this hyaluronic acid-polylysine to deliver exosomes has become a promising therapeutic strategy for myocardial repair.
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Exosomas , Ácido Hialurónico , Hidrogeles , Inflamación , Estrés Oxidativo , Polilisina , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Exosomas/metabolismo , Polilisina/química , Polilisina/farmacología , Polilisina/análogos & derivados , Hidrogeles/química , Animales , Estrés Oxidativo/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/metabolismo , Infarto del Miocardio/terapia , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Ratones , Microambiente Celular/efectos de los fármacos , Masculino , Miocardio/metabolismo , Miocardio/patología , Inyecciones , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Introduction: Persistent endodontic infections (PEIs) mediated by bacterial biofilm mainly cause persistent periapical inflammation, resulting in recurrent periapical abscesses and progressive bone destruction. However, conventional root canal disinfectants are highly damaging to the tooth and periodontal tissue and ineffective in treating persistent root canal infections. Antimicrobial materials that are biocompatible with apical tissues and can eliminate PEIs-associated bacteria are urgently needed. Methods: Here, ε-poly (L-lysine) derived carbon quantum dots (PL-CQDs) are fabricated using pyrolysis to remove PEIs-associated bacterial biofilms. Results: Due to their ultra-small size, high positive charge, and active reactive oxygen species (ROS) generation capacity, PL-CQDs exhibit highly effective antibacterial activity against Enterococcus faecalis (E. faecalis), which is greatly dependent on PL-CQDs concentrations. 100 µg/mL PL-CQDs could kill E. faecalis in 5 min. Importantly, PL-CQDs effectively achieved a reduction of biofilms in the isolated teeth model, disrupting the dense structure of biofilms. PL-CQDs have acceptable cytocompatibility and hemocompatibility in vitro and good biosafety in vivo. Discussion: Thus, PL-CQDs provide a new strategy for treating E. faecalis-associated PEIs.
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Biopelículas , Carbono , Enterococcus faecalis , Infecciones por Bacterias Grampositivas , Polilisina , Puntos Cuánticos , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/fisiología , Puntos Cuánticos/química , Biopelículas/efectos de los fármacos , Polilisina/química , Polilisina/farmacología , Carbono/química , Carbono/farmacología , Animales , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Especies Reactivas de Oxígeno/metabolismo , RatonesRESUMEN
Introduction: The emergence and rapid spread of multidrug-resistant bacteria (MRB) caused by the excessive use of antibiotics and the development of biofilms have been a growing threat to global public health. Nanoparticles as substitutes for antibiotics were proven to possess substantial abilities for tackling MRB infections via new antimicrobial mechanisms. Particularly, carbon dots (CDs) with unique (bio)physicochemical characteristics have been receiving considerable attention in combating MRB by damaging the bacterial wall, binding to DNA or enzymes, inducing hyperthermia locally, or forming reactive oxygen species. Methods: Herein, how the physicochemical features of various CDs affect their antimicrobial capacity is investigated with the assistance of machine learning (ML) tools. Results: The synthetic conditions and intrinsic properties of CDs from 121 samples are initially gathered to form the raw dataset, with Minimum inhibitory concentration (MIC) being the output. Four classification algorithms (KNN, SVM, RF, and XGBoost) are trained and validated with the input data. It is found that the ensemble learning methods turn out to be the best on our data. Also, ε-poly(L-lysine) CDs (PL-CDs) were developed to validate the practical application ability of the well-trained ML models in a laboratory with two ensemble models managing the prediction. Discussion: Thus, our results demonstrate that ML-based high-throughput theoretical calculation could be used to predict and decode the relationship between CD properties and the anti-bacterial effect, accelerating the development of high-performance nanoparticles and potential clinical translation.
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Antibacterianos , Carbono , Aprendizaje Automático , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química , Carbono/química , Carbono/farmacología , Puntos Cuánticos/química , Humanos , Polilisina/química , Polilisina/farmacología , AlgoritmosRESUMEN
ε-Poly-l-lysine (ε-PL) is an effective antimicrobial peptide for controlling fungal plant diseases, exhibiting significant antifungal activity and safety. Despite its known efficacy, the potential of ε-PL in combating plant bacterial diseases remains underexplored. This study evaluated the effectiveness of ε-PL and its nanomaterial derivative in managing tomato bacterial spot disease caused by Pseudomonas syringae pv. tomato. Results indicated that ε-PL substantially inhibited the growth of Pseudomonas syringae pv. tomato. Additionally, when ε-PL was loaded onto attapulgite (encoded as ATT@PL), its antibacterial effect was significantly enhanced. Notably, the antibacterial efficiency of ATT@PL containing 18.80 µg/mL ε-PL was even close to that of 100 µg/mL pure ε-PL. Further molecular study results showed that, ATT@PL stimulated the antioxidant system and the salicylic acid signaling pathway in tomatoes, bolstering the plants disease resistance. Importantly, the nanocomposite demonstrated no negative effects on both seed germination and plant growth, indicating its safety and aligning with sustainable agricultural practices. This study not only confirmed the effectiveness of ε-PL in controlling tomato bacterial spot disease, but also introduced an innovative high antibacterial efficiency ε-PL composite with good bio-safety. This strategy we believe can also be used in improving other bio-pesticides, and has high applicability in agriculture practice.
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Antibacterianos , Enfermedades de las Plantas , Polilisina , Pseudomonas syringae , Compuestos de Silicona , Solanum lycopersicum , Pseudomonas syringae/efectos de los fármacos , Solanum lycopersicum/microbiología , Polilisina/farmacología , Polilisina/química , Antibacterianos/farmacología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Compuestos de Silicona/farmacología , Compuestos de Silicona/química , Compuestos de MagnesioRESUMEN
Microfluidic cell encapsulation has provided a platform for studying the behavior of individual cells and has become a turning point in single-cell analysis during the last decade. The engineered microenvironment, along with protecting the immune response, has led to increasingly presenting the results of practical and pre-clinical studies with the goals of disease treatment, tissue engineering, intelligent control of stem cell differentiation, and regenerative medicine. However, the significance of cell-substrate interaction versus cell-cell communications in the microgel is still unclear. In this study, monodisperse alginate microgels were generated using a flow-focusing microfluidic device to determine how the cell microenvironment can control human bone marrow-derived mesenchymal stem cells (hBMSCs) viability, proliferation, and biomechanical features in single-cell droplets versus multi-cell droplets. Collected results show insufficient cell proliferation (234 % and 329 %) in both single- and multi-cell alginate microgels. Alginate hydrogels supplemented with poly-l-lysine (PLL) showed a better proliferation rate (514 % and 780 %) in a comparison of free alginate hydrogels. Cell stiffness data illustrate that hBMSCs cultured in alginate hydrogels have higher membrane flexibility and migration potency (Young's modulus equal to 1.06 kPa), whereas PLL introduces more binding sites for cell attachment and causes lower flexibility and migration potency (Young's modulus equal to 1.83 kPa). Considering that cell adhesion is the most important parameter in tissue engineering, in which cells do not run away from a 3D substrate, PLL enhances cell stiffness and guarantees cell attachments. In conclusion, cell attachment to PLL-mediated alginate hydrogels is crucial for cell viability and proliferation. It suggests that cell-cell signaling is good enough for stem cell viability, but cell-PLL attachment alongside cell-cell signaling is crucial for stem cell proliferation and self-renewal.
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Alginatos , Adhesión Celular , Proliferación Celular , Células Madre Mesenquimatosas , Microgeles , Polilisina , Alginatos/química , Alginatos/farmacología , Polilisina/química , Polilisina/farmacología , Humanos , Adhesión Celular/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Proliferación Celular/efectos de los fármacos , Microgeles/química , Microfluídica/métodos , Comunicación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Encapsulación Celular/métodos , Análisis de la Célula Individual , Autorrenovación de las Células/efectos de los fármacos , Diferenciación Celular/efectos de los fármacosRESUMEN
Uncontrolled bleeding and wound infections following severe trauma pose significant challenges for existing tissue adhesives, primarily due to their weak wet adhesion, slow adhesion formation, cytotoxicity concerns, and lack of antibacterial properties. Herein, an injectable hydrogel (denoted as ES gel) with rapid, robust adhesive sealing and inherent antibacterial activity based on ε-polylysine and a poly(ethylene glycol) derivative is developed. The engineered hydrogel exhibits rapid gelation behavior, high mechanical strength, strong adhesion to various tissues, and can sustain an ultrahigh burst pressure of 450 mmHg. It also presents excellent biocompatibility, biodegradability, antibacterial properties, and on-demand removability. Significantly improved hemostatic efficacy of ES gel compared to fibrin glue is demonstrated using various injury models in rats and rabbits. Remarkably, the adhesive hydrogel can effectively halt lethal non-compressible hemorrhages in visceral organs (liver, spleen, and heart) and femoral artery injury models in fully anticoagulated pigs. Furthermore, the hydrogel outperforms commercial products in sutureless wound closure and repair in the rat liver defect, skin incision, and infected full-thickness skin wound models. Overall, this study highlights the promising clinical applications of ES gel for managing uncontrolled hemorrhage, sutureless wound closure, and infected wound repair.
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Antibacterianos , Hemostasis , Hidrogeles , Cicatrización de Heridas , Animales , Hidrogeles/química , Hidrogeles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Ratas , Conejos , Hemostasis/efectos de los fármacos , Presión , Polilisina/química , Polilisina/farmacología , Inyecciones , Porcinos , Polietilenglicoles/química , Hemorragia/tratamiento farmacológico , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ratas Sprague-Dawley , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología , Adhesivos Tisulares/uso terapéuticoRESUMEN
The treatment of various types of wounds such as dermal wounds, multidrug resistant bacteria-infected wounds, and chronic diabetic wounds is one of the critical challenges facing healthcare systems. Delayed wound healing can impose a remarkable burden on patients and health care professionals. In this case, given their unique three-dimensional porous structure, biocompatibility, high hydrophilicity, capability to provide a moist environment while absorbing wound exudate, permeability to both gas and oxygen, and tunable mechanical properties, hydrogels with antibacterial function are one of the most promising candidates for wound healing applications. Polylysine is a cationic polymer with the advantages of inherent antibacterial properties, biodegradability, and biocompatibility. Therefore, its utilization to engineer antibacterial hydrogels for accelerating wound healing is of great interest. In this review, we initially discuss polylysine properties, and then focus on the most recent advances in polylysine-containing hydrogels (since 2016) prepared using various chemical and physical crosslinking methods for hemostasis and wound healing applications. Finally, the challenges and future directions in the engineering of these antibacterial hydrogels for wound healing are discussed.
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Antibacterianos , Hidrogeles , Polilisina , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Polilisina/química , Polilisina/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Animales , Hemostáticos/farmacología , Hemostáticos/química , Hemostáticos/administración & dosificación , Hemostasis/efectos de los fármacosRESUMEN
Dental Implants are expected to possess both excellent osteointegration and antibacterial activity because poor osseointegration and infection are two major causes of titanium implant failure. In this study, we constructed layer-by-layer self-assembly films consisting of anionic casein phosphopeptides-amorphous calcium phosphate (CPP-ACP) and cationic poly (L-lysine) (PLL) on sandblasted and acid etched (SLA) titanium surfaces and evaluated their osseointegration and antibacterial performance in vitro and in vivo. The surface properties were examined, including microstructure, elemental composition, wettability, and Ca2+ ion release. The impact the surfaces had on the adhesion, proliferation and differentiation abilities of MC3T3-E1 cells were investigated, as well as the material's antibacterial performance after exposure to the oral microorganisms such as Porphyromonas gingivalis (P. g) and Actinobacillus actinomycetemcomitans (A. a). For the in vivo studies, SLA and Ti (PLL/CA-3.0)10 implants were inserted into the extraction socket immediately after extracting the rabbit mandibular anterior teeth with or without exposure to mixed bacteria solution (P. g & A. a). Three rabbits in each group were sacrificed to collect samples at 2, 4, and 6 weeks of post-implantation, respectively. Radiographic and histomorphometry examinations were performed to evaluate the implant osseointegration. The modified titanium surfaces were successfully prepared and appeared as a compact nano-structure with high hydrophilicity. In particular, the Ti (PLL/CA-3.0)10 surface was able to continuously release Ca2+ ions. From the in vitro and in vivo studies, the modified titanium surfaces expressed enhanced osteogenic and antibacterial properties. Hence, the PLL/CPP-ACP multilayer coating on titanium surfaces was constructed via a layer-by-layer self-assembly technology, possibly improving the biofunctionalization of Ti-based dental implants.
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Antibacterianos , Oseointegración , Polilisina , Propiedades de Superficie , Titanio , Titanio/química , Titanio/farmacología , Oseointegración/efectos de los fármacos , Animales , Polilisina/química , Polilisina/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Ratones , Implantes Dentales/microbiología , Conejos , Porphyromonas gingivalis/efectos de los fármacos , Caseínas/química , Caseínas/farmacología , Proliferación Celular/efectos de los fármacos , Aggregatibacter actinomycetemcomitans/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Fosfatos de CalcioRESUMEN
Biomaterial properties have recently been shown to modulate extracellular vesicle (EV) secretion and cargo; however, the effects of substrate composition on EV production remain underexplored. This study investigates the impacts of surface coatings composed of collagen I (COLI), fibronectin (FN), and poly l-lysine (PLL) on EV secretion for applications in therapeutic EV production and to further understanding of how changes in the extracellular matrix microenvironment affect EVs. EV secretion from primary bone marrow-derived mesenchymal stromal cells (BMSCs), primary adipose-derived stem cells (ASCs), HEK293 cells, NIH3T3 cells, and RAW264.7 cells was characterized on the different coatings. Expression of EV biogenesis genes and cellular adhesion genes was also analyzed. COLI coatings significantly decreased EV secretion in RAW264.7 cells, with associated decreases in cell viability and changes in EV biogenesis-related and cell adhesion genes at day 4. FN coatings increased EV secretion in NIH3T3 cells, while PLL coatings increased EV secretion in ASCs. Surface coatings had significant effects on the capacity of EVs derived from RAW264.7 and NIH3T3 cells to impact in vitro macrophage proliferation. Overall, surface coatings had different cell-specific effects on EV secretion and in vitro functional capacity, thus highlighting the potential of substrate coatings to further the development of clinical EV production systems.
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Vesículas Extracelulares , Fibronectinas , Células Madre Mesenquimatosas , Ratones , Animales , Humanos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Células 3T3 NIH , Células RAW 264.7 , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Fibronectinas/química , Fibronectinas/metabolismo , Propiedades de Superficie , Polilisina/química , Polilisina/farmacología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Células HEK293 , Proliferación Celular/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colágeno Tipo I/metabolismo , Colágeno Tipo I/química , Colágeno Tipo I/genéticaRESUMEN
Salmonella is capable of surviving dehydration within various foods, such as dried fruit. Dried fruit, including apple slices, have been the subject of product recalls due to contamination with Salmonella. A study was conducted to determine the fate of Salmonella on apple slices, following immersion in three antimicrobial solutions (viz., ε-polylysine [epsilon-polylysine or EP], sodium bisulfate [SBS], or peracetic acid [PAA]), and subsequent hot air dehydration. Gala apples were aseptically cored and sliced into 0.4 cm thick rings, bisected, and inoculated with a five-strain composite of desiccation-resistant Salmonella, to a population of 8.28 log CFU/slice. Slices were then immersed for 2 min in various concentrations of antimicrobial solutions, including EP (0.005, 0.02, 0.05, and 0.1%), SBS (0.05, 0.1, 0.2, and 0.3%), PAA (18 or 42 ppm), or varying concentrations of PAA + EP, and then dehydrated at 60°C for 5 h. Salmonella populations in positive control samples (inoculated apple slices washed in sterile water) declined by 2.64 log after drying. In the present study, the inactivation of Salmonella, following EP and SBS treatments, increased with increasing concentrations, with maximum reductions of 3.87 and 6.20 log (with 0.1 and 0.3% of the two compounds, respectively). Based on preliminary studies, EP concentrations greater than 0.1% did not result in lower populations of Salmonella. Pretreatment washes with either 18 or 42 ppm of PAA inactivated Salmonella populations by 4.62 and 5.63 log, respectively, following desiccation. Combining PAA with up to 0.1% EP induced no greater population reductions of Salmonella than washing with PAA alone. The addition of EP to PAA solutions appeared to destabilize PAA concentrations, reducing its biocidal efficacy. These results may provide antimicrobial predrying treatment alternatives to promote the reduction of Salmonella during commercial or consumer hot air drying of apple slices.
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Recuento de Colonia Microbiana , Microbiología de Alimentos , Malus , Ácido Peracético , Polilisina , Salmonella , Malus/microbiología , Ácido Peracético/farmacología , Salmonella/efectos de los fármacos , Polilisina/farmacología , Humanos , Sulfatos/farmacología , Conservación de Alimentos/métodos , Relación Dosis-Respuesta a Droga , Desecación , Contaminación de Alimentos/análisis , Manipulación de Alimentos/métodos , Seguridad de Productos para el ConsumidorRESUMEN
The biggest obstacle to treating wound healing continues to be the production of simple, inexpensive wound dressings that satisfy the demands associated with full process of repair at the same time. Herein, a series of injectable composite hydrogels were successfully prepared by a one-pot method by utilizing the Schiff base reaction as well as hydrogen bonding forces between hydroxypropyl chitosan (HCS), ε-poly-l-lysine (EPL), and 2,3,4-trihydroxybenzaldehyde (TBA), and multiple cross-links formed by the reversible coordination between iron (III) and pyrogallol moieties. Notably, hydrogel exhibits excellent physicochemical properties, including injectability, self-healing, water retention, and adhesion, which enable to fill irregular wounds for a long period, providing a suitable moist environment for wound healing. Interestingly, the excellent hemostatic properties of the hydrogel can quickly stop bleeding and avoid the serious sequelae of massive blood loss in acute trauma. Moreover, the powerful antimicrobial and antioxidant properties also protect against bacterial infections and reduce inflammation at the wound site, thus promoting healing at all stages of the wound. The study of biohydrogel with multifunctional integration of wound treatment and smart medical treatment is clarified by this line of research.
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Quitosano , Hemostáticos , Hidrogeles , Polilisina , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Quitosano/química , Quitosano/farmacología , Quitosano/análogos & derivados , Polilisina/química , Polilisina/farmacología , Animales , Hemostáticos/química , Hemostáticos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Ratones , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Humanos , Antiinfecciosos/farmacología , Antiinfecciosos/química , Bases de Schiff/química , Bases de Schiff/farmacología , RatasRESUMEN
This study investigated the synergistic effects of ε-poly- L -lysine (ε-PL) and lysozyme against P. aeruginosa and L. monocytogenes biofilms. Single-culture biofilms of two bacteria were formed on silicone rubber (SR), stainless steel (SS), and beef surfaces and then treated with lysozyme (0.05-5 mg/mL) and ε-PL at minimum inhibitory concentrations (MICs) of 1 to 4 separately or in combination. On the SR surface, P. aeruginosa biofilm was reduced by 1.4 and 1.9 log CFU/cm2 within 2 h when treated with lysozyme (5 mg/mL) and ε-PL (4 MIC), respectively, but this reduction increased significantly to 4.1 log CFU/cm2 (P < 0.05) with the combined treatment. On beef surface, P. aeruginosa and L. monocytogenes biofilm was reduced by 4.2-5.0, and 3.3-4.2 log CFU/g when lysozyme was combined with 1, 2, and 4 MIC of ε-PL at 25 °C, respectively. Compared to 5 mg/mL lysozyme alone, the combined treatment with 1, 2, and 4 MIC of ε-PL on beef surface achieved additional reduction against P. aeruginosa biofilm of 0.5, 0.8, and 0.7 log CFU/g, respectively, at 25 °C. In addition, 0.25 mg/mL lysozyme and 0.5 MIC of ε-PL significantly (P < 0.05) suppressed the quorum-sensing (agrA) and virulence-associated (hlyA and prfA) genes of L. monocytogenes.
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Biopelículas , Listeria monocytogenes , Muramidasa , Polilisina , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efectos de los fármacos , Muramidasa/farmacología , Biopelículas/efectos de los fármacos , Animales , Listeria monocytogenes/efectos de los fármacos , Polilisina/farmacología , Bovinos , Sinergismo Farmacológico , Pruebas de Sensibilidad Microbiana , Carne Roja/microbiología , Microbiología de Alimentos , Acero Inoxidable , Antibacterianos/farmacologíaRESUMEN
Traditional Chinese medicine external prescriptions have displayed excellent clinical effects for treating deep soft tissue injuries. However, the effects cannot be fully utilized due to the limitations of their dosage forms and usage methods. It is still a challenge to develop a satisfactory adjuvant of traditional Chinese medicine external prescriptions. Herein, a hydrogel adjuvant was prepared based on gallic acid coupled ε-poly-l-lysine and partially oxidized hyaluronic acid. The resulting adjuvant shows great physicochemical properties, low hemolysis rate (still much less than 5% at 5 mg/mL), excellent antibacterial ability (about 95% at 2 mg/mL), strong antioxidant ability (1.687 ± 0.085 mmol FeSO4/(g hydrogel) at 1 mg/mL), as well as outstanding biocompatibility. A clinically used Chinese medicine external preparation was selected as an example to investigate the effectiveness of the adjuvant in treating deep soft tissue injuries. The results show that the prescription can be evenly dispersed in the adjuvant. Moreover, the introduction of the prescription has not significantly changed these advanced properties of the adjuvant. Importantly, the hydrogel adjuvant significantly improves the effectiveness of the prescription in treating deep soft tissue injuries. This work offers an alternative approach to the development of a new-type adjuvant of Chinese medicine external preparations and also provides a new strategy for the combination of traditional Chinese medicine and hydrogel to treat clinical diseases.
Asunto(s)
Medicamentos Herbarios Chinos , Hidrogeles , Traumatismos de los Tejidos Blandos , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Animales , Cicatrización de Heridas/efectos de los fármacos , Traumatismos de los Tejidos Blandos/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ácido Hialurónico/química , Ácido Hialurónico/uso terapéutico , Ácido Hialurónico/farmacología , Medicina Tradicional China , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/química , Ácido Gálico/química , Ácido Gálico/farmacología , Ácido Gálico/uso terapéutico , Polilisina/química , Polilisina/farmacología , Polilisina/uso terapéutico , Humanos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Hemólisis/efectos de los fármacos , RatonesRESUMEN
Blood-contacting catheters play a pivotal role in contemporary medical treatments, particularly in the management of cardiovascular diseases. However, these catheters exhibit inappropriate wettability and lack antimicrobial characteristics, which often lead to catheter-related infections and thrombosis. Therefore, there is an urgent need for blood contact catheters with antimicrobial and anticoagulant properties. In this study, we employed tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) to create a stable hydrophilic coating under mild conditions. Heparin (Hep) and poly(lysine) (PL) were then modified on the TA-APTES coating surface using the layer-by-layer (LBL) technique to create a superhydrophilic TA/APTES/(LBL)4 coating on silicone rubber (SR) catheters. Leveraging the superhydrophilic nature of this coating, it can be effectively applied to blood-contacting catheters to impart antibacterial, antiprotein adsorption, and anticoagulant properties. Due to Hep's anticoagulant attributes, the activated partial thromboplastin time and thrombin time tests conducted on SR/TA-APTES/(LBL)4 catheters revealed remarkable extensions of 276 and 103%, respectively, when compared to uncoated commercial SR catheters. Furthermore, the synergistic interaction between PL and TA serves to enhance the resistance of SR/TA-APTES/(LBL)4 catheters against bacterial adherence, reducing it by up to 99.9% compared to uncoated commercial SR catheters. Remarkably, the SR/TA-APTES/(LBL)4 catheter exhibits good biocompatibility with human umbilical vein endothelial cells in culture, positioning it as a promising solution to address the current challenges associated with blood-contact catheters.
Asunto(s)
Catéteres , Materiales Biocompatibles Revestidos , Heparina , Polifenoles , Taninos , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Humanos , Catéteres/microbiología , Polifenoles/química , Polifenoles/farmacología , Heparina/química , Heparina/farmacología , Taninos/química , Taninos/farmacología , Silanos/química , Silanos/farmacología , Anticoagulantes/química , Anticoagulantes/farmacología , Propilaminas/química , Aminas/química , Aminas/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Polilisina/química , Polilisina/farmacología , Propiedades de Superficie , Interacciones Hidrofóbicas e Hidrofílicas , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Elastómeros de Silicona/química , Adsorción , Escherichia coli/efectos de los fármacosRESUMEN
Skin wounds are susceptible to infection, leading to severe inflammatory reactions that can progress to chronic wounds, ultimately causing significant physical and mental distress to the patient. In this study, we propose an injectable composite hydrogel achieved through one-pot gelation of oxidized xyloglucan (OXG), cationic polyamide ε-poly-l-lysine (EPL), and surface amino-rich silicon nanoparticles (SiNPs). OXG exhibits commendable anti-inflammatory properties and provides crosslinking sites. SiNPs serve as mechanically reinforced crosslinkers, facilitating the construction of a dynamic Schiff base network. SiNPs significantly reduced the gelation time to 3 s and tripled the storage modulus of the hydrogels. Additionally, the combination of EPL and SiNPs demonstrated synergistic antimicrobial activity against both S. aureus and E. coli. Notably, the hydrogel effectively halted liver bleeding within 30 s. The hydrogel demonstrated outstanding shear-thinning and self-healing properties, crucial considerations for the design of injectable hydrogels. Furthermore, its efficacy was evaluated as a wound dressing in a mouse model with S. aureus infection. The results indicated that, compared to commercial products, the hydrogel exhibited a shorter wound healing time, decreased inflammation, thinner epithelium, increased hair follicles, enhanced neovascularization, and more substantial collagen deposition. These findings strongly suggest the promising potential of the proposed hydrogel as an effective wound dressing for the treatment of infected wounds.
Asunto(s)
Antibacterianos , Escherichia coli , Glucanos , Hidrogeles , Nanopartículas , Polilisina , Staphylococcus aureus , Cicatrización de Heridas , Xilanos , Glucanos/química , Glucanos/farmacología , Animales , Cicatrización de Heridas/efectos de los fármacos , Xilanos/química , Xilanos/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Polilisina/química , Polilisina/farmacología , Ratones , Nanopartículas/química , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Infecciones Estafilocócicas/tratamiento farmacológico , Reactivos de Enlaces Cruzados/química , Infección de Heridas/tratamiento farmacológico , MasculinoRESUMEN
Combating antimicrobial resistance is one of the biggest health challenges because of the ineffectiveness of standard biocide treatments. This challenge could be approached using natural products, which have demonstrated powerful therapeutics against multidrug-resistant microbes. In the present work, a nanodevice consisting of mesoporous silica nanoparticles loaded with an essential oil component (cinnamaldehyde) and functionalized with the polypeptide ε-poly-l-lysine is developed and used as an antimicrobial agent. In the presence of the corresponding stimuli (i.e., exogenous proteolytic enzymes from bacteria or fungi), the polypeptide is hydrolyzed, and the cinnamaldehyde delivery is enhanced. The nanodevice's release mechanism and efficacy are evaluated in vitro against the pathogenic microorganisms Escherichia coli, Staphylococcus aureus, and Candida albicans. The results demonstrate that the new device increases the delivery of the cinnamaldehyde via a biocontrolled uncapping mechanism triggered by proteolytic enzymes. Moreover, the nanodevice notably improves the antimicrobial efficacy of cinnamaldehyde when compared to the free compound, ca. 52-fold for E. coli, ca. 60-fold for S. aureus, and ca. 7-fold for C. albicans. The enhancement of the antimicrobial activity of the essential oil component is attributed to the decrease of its volatility due to its encapsulation in the porous silica matrix and the increase of its local concentration when released due to the presence of microorganisms.
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Acroleína , Acroleína/análogos & derivados , Antiinfecciosos , Candida albicans , Escherichia coli , Nanopartículas , Dióxido de Silicio , Staphylococcus aureus , Acroleína/farmacología , Acroleína/química , Nanopartículas/química , Escherichia coli/efectos de los fármacos , Candida albicans/efectos de los fármacos , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Staphylococcus aureus/efectos de los fármacos , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/administración & dosificación , Porosidad , Pruebas de Sensibilidad Microbiana , Polilisina/química , Polilisina/farmacologíaRESUMEN
MicroRNAs (miRNAs) play important roles in plant defense against various pathogens. ε-poly-l-lysine (ε-PL), a natural anti-microbial peptide produced by microorganisms, effectively suppresses tobacco mosaic virus (TMV) infection. To investigate the anti-viral mechanism of ε-PL, the expression profiles of miRNAs in TMV-infected Nicotiana tabacum after ε-PL treatment were analyzed. The results showed that the expression levels of 328 miRNAs were significantly altered by ε-PL. Degradome sequencing was used to identify their target genes. Integrative analysis of miRNAs target genes and gene-enriched GO/KEGG pathways indicated that ε-PL regulates the expression of miRNAs involved in critical pathways of plant hormone signal transduction, host defense response, and plant pathogen interaction. Subsequently, virus induced gene silencing combined with the short tandem targets mimic technology was used to analyze the function of these miRNAs and their target genes. The results indicated that silencing miR319 and miR164 reduced TMV accumulation in N. benthamiana, indicating the essential roles of these miRNAs and their target genes during ε-PL-mediated anti-viral responses. Collectively, this study reveals that microbial source metabolites can inhibit plant viruses by regulating crucial host miRNAs and further elucidate anti-viral mechanisms of ε-PL.