RESUMO
Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.
Assuntos
Células Dendríticas , Hidrogéis , Melanoma , Cicatrização , Hidrogéis/química , Animais , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Melanoma/terapia , Melanoma/patologia , Cicatrização/efeitos dos fármacos , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Camundongos Endogâmicos C57BL , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/farmacologia , Camundongos , Linhagem Celular Tumoral , FemininoRESUMO
Green synthesis leverages biological resources such as plant extracts to produce cost-effectively and environmentally friendly NPs. In our study, silver nanoparticles (AgNPs) are biosynthesized using blank roasted grams (Cicer arietinum) as reducing agents. CA-AgNPs were characterized by a characteristic surface plasmon resonance (SPR) peak at 224 nm in the UV-Vis spectrum. FTIR analysis revealed functional groups with O-H stretching at 3410 cm-1, C-H stretching at 2922 cm-1, and C=O stretching at 1635 cm-1. XRD patterns exhibited sharp peaks at 33.2°, 38.4°, 55.7°, and 66.6°, confirming high crystallinity. Morphological analysis through FESEM indicated spherical CA-AgNPs averaging 500 nm in size, with EDS revealing Ag at 97.51% by weight. Antimicrobial assays showed zones of inhibition of 14 mm against Candida albicans, 18 mm against Escherichia coli., and 12 mm against Propionibacterium acnes. The total phenolic content of CA-AgNPs was 26.17 ± 13.54 mg GAE/g, significantly higher than the 11.85 ± 9.57 mg GAE/g in CA extract. The ABTS assay confirmed the antioxidant potential with a lower IC50 value of 1.73 ± 0.41 µg/mL, indicating enhanced radical scavenging activity. Anti-melanogenesis was validated through tyrosinase, showing inhibition rates of 97.97% at the highest concentrations. The anti-inflammatory was evaluated by western blot, which showed decreased expression of iNOS and COX-2. This study demonstrates the green synthesis of CA-AgNPs and its potential biomedical applications. The results of this study demonstrate that biosynthesized CA-AgNPs have key biological applications.
Assuntos
Cicer , Química Verde , Nanopartículas Metálicas , Extratos Vegetais , Prata , Prata/química , Nanopartículas Metálicas/química , Cicer/química , Química Verde/métodos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Testes de Sensibilidade Microbiana , Animais , Candida albicans/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
BACKGROUND The environmentally friendly production of silver nanoparticles (AgNPs) has gained significant attention as a sustainable alternative to traditional chemical methods. This study focused on synthesizing AgNPs using extract of Dracocephalum kotschyi (D. kotschyi), a medicinal plant. MATERIAL AND METHODS The biosynthesis of AgNPs was monitored using UV-visible spectrophotometry. The role of phytoconstituents from D. kotschyi in stabilizing AgNPs was analyzed using Fourier-transform infrared (FTIR) spectroscopy. Dynamic light scattering (DLS) spectroscopy was used to determine the size, charge, and polydispersity of the nanoparticles, while scanning electron microscopy (SEM) was employed to assess their morphology. We evaluated the antimicrobial efficacy of the synthesized AgNPs against various bacteria, their antioxidant properties via a 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay, and their cytotoxic activity against the HeLa cervical cancer cell line. RESULTS The formation of AgNPs was indicated by a color change and the emergence of a surface plasmon resonance peak at 418 nm. The nanoparticles demonstrated significant antimicrobial, antioxidant, cytotoxic, and anticancer activities. Morphology, size, and shape analysis revealed nearly spherical particles with an average size of 43 nm. FTIR confirmed the presence of phenolic compounds in the extract, serving as reducing and capping agents. X-ray diffraction (XRD) analysis confirmed the crystalline structure of the nanoparticles. Antimicrobial assessments showed effectiveness against Escherichia coli and Staphylococcus aureus. The DPPH scavenging assay demonstrated efficient antioxidant activity, and potent apoptotic anticancer effects were observed on cervical cancer cells. CONCLUSIONS The extract of D. kotschyi was effective as a reducing agent in the environmentally friendly synthesis of AgNPs, which exhibited noteworthy antimicrobial, antioxidant, and anticancer properties. These findings suggest potential biomedical applications for the synthesized AgNPs.
Assuntos
Anti-Infecciosos , Antineoplásicos , Antioxidantes , Química Verde , Nanopartículas Metálicas , Extratos Vegetais , Prata , Nanopartículas Metálicas/química , Prata/farmacologia , Prata/química , Antioxidantes/farmacologia , Antioxidantes/síntese química , Antioxidantes/química , Humanos , Química Verde/métodos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/síntese química , Células HeLa , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Testes de Sensibilidade Microbiana , Lamiaceae/química , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos/farmacologia , Antibacterianos/síntese química , Staphylococcus aureus/efeitos dos fármacosRESUMO
Controlling multidrug-resistant microorganisms (MRM) has a long history with the extensive and inappropriate use of antibiotics. At the cost of these drugs being scarce, new possibilities have to be explored to inhibit the growth of microorganisms. Thus, metallic compounds have shown to be promising as a viable alternative to contain pathogens resistant to conventional antimicrobials. Gallium (Ga3+) can be highlighted, which is an antimicrobial agent capable of disrupting the essential activities of microorganisms, such as metabolism, cellular respiration and DNA synthesis. It was observed that this occurs due to the similar properties between Ga3+ and iron (Fe3+), which is a fundamental ion for the correct functioning of bacterial activities. The mimetic effect performed by Ga3+ prevents iron transporters from distinguishing both ions and results in the substitution of Fe3+ for Ga3+ and in adverse metabolic disturbances in rapidly growing cells. This review focuses on analyzing the development of research involving Ga3+, elucidating the intracellular incorporation of the "Trojan Horse", summarizing the mechanism of interaction between gallium and iron and comparing the most recent and broad-spectrum studies using gallium-based compounds with antimicrobial scope.
Assuntos
Bactérias , Gálio , Ferro , Gálio/farmacologia , Gálio/metabolismo , Ferro/metabolismo , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Antibacterianos/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Anti-Infecciosos/farmacologia , Anti-Infecciosos/metabolismoRESUMO
This study investigates the colonization of endophytic fungi in nettle leaf tissues and evaluates their antibacterial and antioxidant activities. Using an inverted optical microscope, extensive fungal colonization was observed in all leaf parts, with hyphae prevalent in epidermal cells, parenchyma cells, and vascular tissues. 144 endophytic fungal isolates were isolated from 800 leaf fragments, indicating an 18% retention rate. ANOVA analysis revealed significant differences (p < 0. 001) in colonization frequencies among 20 subjects, with subject 3 showing the highest frequency (40%) and subject 11 the lowest (2. 5%). Ethyl acetate extracts of the three most abundant endophytic fungi demonstrated notable antibacterial activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Inhibition zones ranged from 9. 5 to 15. 16 mm, with minimum inhibitory concentrations (MICs) between 0. 19 to 25 mg/mL. Alternaria sp. exhibited the highest antimicrobial activity against MRSA. Antioxidant activity was assessed using the DPPH radical scavenging test and FRAP method. All extracts showed substantial free radical scavenging properties, with IC50 values close to those of standards like BHT. Alternaria sp. had the highest antioxidant activity, followed by Epicocum sp. and Ulocladium sp. The FRAP method confirmed high reducing potential, with Alternaria sp. again exhibiting the highest activity. These findings highlight the potential of endophytic fungi in nettle leaves as sources of antimicrobial and antioxidant agents, with significant implications for pharmaceutical and biotechnological applications.
Assuntos
Anti-Infecciosos , Antioxidantes , Endófitos , Fungos , Testes de Sensibilidade Microbiana , Folhas de Planta , Antioxidantes/farmacologia , Antioxidantes/química , Fungos/efeitos dos fármacos , Endófitos/química , Folhas de Planta/microbiologia , Folhas de Planta/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Paint is a versatile material that can be used to coat surfaces for which routine disinfection practices may be lacking. EPA-registered copper-containing supplemental residual antimicrobial paints could be used to reduce the bioburden on often-neglected surfaces. An interventional study was conducted by painting the walls of a preschool restroom and metal locker surfaces in two hospital locker rooms with a copper-containing antimicrobial paint to evaluate the potential for bioburden reduction compared to a non-copper-containing control paint. The antimicrobial paint reduced the bioburden on the preschool restroom walls by 57% and on lockers in one locker room by 63% compared to the control paint; no significant difference was observed between the two paint types in the second locker room. The upper quartile bacterial counts, which drive the overall risk by increasing exposure to pathogens, also exhibited 63% and 47% reductions for the antimicrobial paint compared to the control paint in the preschool restroom and the first locker room, respectively. Because detectible levels of bioburden are found on large-area surfaces such as walls and lockers, surfaces painted with copper-containing paints may make large-area surfaces that are prone to contamination safer in a way that is practical and economical.
Assuntos
Anti-Infecciosos , Desinfecção , Pintura , Pintura/análise , Desinfecção/métodos , Anti-Infecciosos/farmacologia , Humanos , Cobre/farmacologia , Propriedades de SuperfícieRESUMO
The high incidence and mortality rates associated with acute and chronic wound infections impose a significant burden on global healthcare systems. In terms of the management of wound infection, the reconstruction and regeneration of skin appendages are essential for the recovery of mechanical strength and physiological function in the regenerated skin tissue. Novel therapeutic approaches are a requisite for enhancing the healing of infected wounds and promoting the regeneration of skin appendages. Herein, a novel antimicrobial microneedle patch has been fabricated for the transdermal controlled delivery of adipose tissue-derived apoptotic vesicles (ApoEVs-AT@MNP) for the treatment of infected wounds, which is expected to achieve high-quality scarless healing of the wound skin while inhibiting the bacteria in the infected wound. The microneedle patch (MNP) system possesses adequate mechanical strength to penetrate the skin, allowing the tips to remain inside tissue for continuous active release of biomolecules, and subsequently degrades safely within the host body. In vivo transplantation demonstrates that ApoEVs-AT@MNP not only inhibits bacterial proliferation in infected wounds but also significantly promotes effective and rapid scarless wound healing. Particularly noteworthy is the ability of ApoEVs-AT@MNP to promote the rapid formation of mature, evenly arranged hair follicles in infected wounds, observed as early as 8 days following implantation, which is essential for the restoration of skin function. This rapid development of skin appendages has not been reported this early in previous studies. Therefore, ApoEVs-AT@MNP has emerged as an excellent, painless, non-invasive, and highly promising treatment for infected wounds.
Assuntos
Tecido Adiposo , Apoptose , Agulhas , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Tecido Adiposo/citologia , Camundongos , Apoptose/efeitos dos fármacos , Pele/efeitos dos fármacos , Masculino , Antibacterianos/farmacologia , Antibacterianos/química , Vesículas Extracelulares/química , Infecção dos Ferimentos/tratamento farmacológico , Anti-Infecciosos/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Camundongos Endogâmicos BALB CRESUMO
Antibiotic resistance has emerged as a global threat, rendering the existing conventional treatment strategies ineffective. In view of this, antimicrobial peptides (AMPs) have proven to be potent alternative therapeutic interventions with a wide range of applications in clinical health. AMPs are small peptides produced naturally as a part of the innate immune responses against a broad range of bacterial, fungal and viral pathogens. AMPs present a myriad of advantages over traditional antibiotics, including their ability to target multiple sites, reduced susceptibility to resistance development, and high efficacy at low doses. These peptides have demonstrated notable potential in inhibiting microbes resistant to traditional antibiotics, including the notorious ESKAPE pathogens, recognized as the primary culprits behind nosocomial infections. AMPs, with their multifaceted benefits, emerge as promising candidates in the ongoing efforts to combat the escalating challenges posed by antibiotic resistance. This in-depth review provides a detailed discussion on AMPs, encompassing their classification, mechanism of action, and diverse clinical applications. Focus has been laid on combating newly emerging drug-resistant organisms, emphasizing the significance of AMPs in mitigating this pressing challenge. The review also illuminates potential future strategies that may be implemented to improve AMP efficacy, such as structural modifications and using AMPs in combination with antibiotics and matrix-inhibiting compounds.
Assuntos
Peptídeos Antimicrobianos , Bactérias , Humanos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Bactérias/efeitos dos fármacos , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Fungos/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Farmacorresistência Bacteriana , Peptídeos Catiônicos Antimicrobianos/farmacologia , Animais , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologiaRESUMO
Nanotechnology is a treasure trove of diversified themes which are endowed with broad applications. Herein, iron oxide (Fe2O3) nanoparticles were synthesized using Phyllanthus emblica aqueous fruit extract. The UV-Visible spectrum exhibited a surface plasmon resonance peak at 295nm. Fourier Transform Infrared Spectroscopy provided insight into the functional groups responsible for capping. X-ray diffraction analysis authenticated the crystalline nature of nanoparticles, while energy dispersive X-ray spectroscopy divulged that iron and oxygen comprised 54% of the nanoparticles' weight. Scanning electron microscopy established irregular morphology and agglomeration of nanoparticles. The Fe2O3 nanoparticles validated potent antimicrobial activity against 11 bacterial and 1 fungal isolates. The biggest zone of inhibition (23mm) was measured against S. enterica, whereas the smallest zone of inhibition (12mm) was documented against C. albicans and E. coli. The values for minimum inhibitory concentration ranged between 10 and 15µg/ml for all microbes. Nevertheless, no synergy was exhibited by the nanoparticles with any of the selected antibiotics (Fractional Inhibitory Concentration Index > 1). The photocatalytic dye degradation capability of Fe2O3 nanoparticles was assessed and the observations implied a significant increase in degradation of methyl red although, not of methylene blue. Furthermore, the nanoparticles were in possession of substantial antioxidant (34-38%) and anti-inflammatory (31-38%) capacities. Consequent upon the robust activities of P. emblica-mediated nanoparticles, these can be scrutinized for biomedical and environmental implementations in future.
Assuntos
Frutas , Testes de Sensibilidade Microbiana , Phyllanthus emblica , Extratos Vegetais , Phyllanthus emblica/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Frutas/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Nanopartículas Magnéticas de Óxido de Ferro/química , Difração de Raios X , Compostos Férricos/química , Candida albicans/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
OBJECTIVE: To determine the effects of adding a quaternary ammonium methacryloxy silicate (K18) and K18-functionalized filler (K18-Filler) on the material and antimicrobial properties of a hard denture reline material. MATERIALS AND METHODS: 30% K18 in methyl methacrylate (K18-MMA; 0-20 wt% of reliner) and K18-Filler (0-30 wt% of reliner) were incorporated into KoolinerTM hard denture reliner. KoolinerTM served as the control. The cure (Shore A hardness), hydrophilicity (contact angles), mechanical (3-point bend test), water sorption, and antimicrobial properties against Streptococcus mutans, S. sanguinis, and Candida albicans were determined. RESULTS: Most K18 groups cured well and had comparable Shore A hardness values (range ~52 to 70 DHN) to that of controls (67.2 ± 1.8 DHN; Bonferroni corrected p > 0.0003). Even the softest group had hardness values within the range of commercial products. Half of the K18 groups had comparable contact angles to that of controls (range ~75° to 80° vs 83.41° ± 2.66°; Bonferroni corrected p > 0.0003), and most were within the range of commercial liners. K18-MMA and K18-Filler increased modulus but decreased ultimate transverse strength (UTS). All experimental groups had comparable or higher moduli than controls (range ~966 to 2069 MPa vs 1340 ± 119 MPa; Bonferroni corrected p < 0.0003), but only half of the experimental groups had comparable UTS to that of controls (range ~41 to 49 MPa vs 55.8 ± 1.5 MPa; Bonferroni corrected p > 0.0003). The 15% and 20% K18-MMA with 30% K18-Filler groups had significant antimicrobial activity against all three microbes (p < 0.05). However, the 15% and 20% K18-MMA with 30% K18-Filler groups had significantly higher water sorption at early time points (p < 0.05). After 8 weeks, they were comparable to each other (p > 0.05). CONCLUSIONS: K18-MMA and K18-Filler are promising antimicrobial additives that produce hard denture liners with material properties within the range of commercial products and significant antimicrobial properties against S. mutans, S. sanguinis, and C. albicans. Further development is needed to reduce water sorption.
Assuntos
Anti-Infecciosos , Candida albicans , Compostos de Amônio Quaternário , Streptococcus mutans , Candida albicans/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Silicatos/química , Reembasadores de Dentadura , Teste de Materiais , Dureza , Metacrilatos/químicaRESUMO
Agricultural yields are often limited by damage caused by pathogenic microorganisms, including plant-pathogenic bacteria. The chemical control options to cope with bacterial diseases in agriculture are limited, predominantly relying on copper-based products. These compounds, however, possess limited efficacy. Therefore, there is an urgent need to develop novel technologies to manage bacterial plant diseases and reduce food loss. In this study, a new antimicrobial agent was developed using a doping method that entraps small bioactive organic molecules inside copper as the metal matrix. The food preservative agent lauroyl arginate ethyl ester (ethyl lauroyl arginate; LAE) was chosen as the doped organic compound. The new composites were termed LAE@[Cu]. Bactericidal assays against Acidovorax citrulli, a severe plant pathogen, revealed that LAE and copper in the composites possess a synergistic interaction as compared with each component individually. LAE@[Cu] composites were further characterised in terms of chemical properties and in planta assays demonstrated their potential for further development as crop protection agents.
Assuntos
Cobre , Proteção de Cultivos , Doenças das Plantas , Cobre/química , Cobre/farmacologia , Proteção de Cultivos/métodos , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Comamonadaceae/efeitos dos fármacos , Comamonadaceae/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Arginina/química , Arginina/farmacologia , Arginina/análogos & derivados , Antibacterianos/farmacologia , Antibacterianos/química , Viabilidade Microbiana/efeitos dos fármacosRESUMO
The rapid resistance developed by pathogenic microorganisms against the current antimicrobial pool represents a serious global public health problem, leading to the search for new antibiotic agents. The scorpion Tityus stigmurus, an abundant species in Northeastern Brazil, presents a rich arsenal of bioactive molecules in its venom, with high potential for biotechnological applications. However, venom cytotoxicity constitutes a barrier to the therapeutic application of its different components. The objective of this study was to produce T. stigmurus-venom-loaded cross-linked chitosan nanoparticles (Tsv/CN) at concentrations of 0.5% and 1.0% to improve their biological antimicrobial activity. Polymeric nanoparticles were formed with a homogeneous particle size and spherical shape. Experimental formulation parameters were verified in relation to mean size (<180 nm), zeta potential, polydispersity index and encapsulation efficiency (>78%). Tsv/CN 1.0% demonstrated an ability to increase the antimicrobial venom effect against Staphylococcus aureus bacteria, exhibiting an MIC value of 44.6 µg/mL. It also inhibited different yeast species of the Candida genus, and Tsv/CN 0.5% and 1.0% led to a greater inhibitory effect of C. tropicalis and C. parapsilosis strains, presenting MIC values between 22.2 and 5.5 µg/mL, respectively. These data demonstrate the biotechnological potential of these nanosystems to obtain a new therapeutic agent with potential antimicrobial activity.
Assuntos
Quitosana , Testes de Sensibilidade Microbiana , Nanopartículas , Venenos de Escorpião , Escorpiões , Quitosana/química , Quitosana/farmacologia , Nanopartículas/química , Animais , Venenos de Escorpião/química , Venenos de Escorpião/farmacologia , Escorpiões/química , Staphylococcus aureus/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Candida/efeitos dos fármacos , Tamanho da Partícula , Antibacterianos/farmacologia , Antibacterianos/química , Animais PeçonhentosRESUMO
Over the last ten years, researchers' efforts have aimed to replace the classic linear economy model with the circular economy model, favoring green chemical and industrial processes. From this point of view, biologically active molecules, coming from plants, flowers and biomass, are gaining considerable value. In this study, firstly we focus on the development of a green protocol to obtain the purification of anthocyanins from the flower of Callistemon citrinus, based on simulation and on response surface optimization methodology. After that, we utilize them to manufacture and add new properties to bioplastics belonging to class 3, based on modified polyvinyl alcohol (PVA) with increasing amounts from 0.10 to 1.00%. The new polymers are analyzed to monitor morphological changes, optical properties, mechanical properties and antioxidant and antimicrobial activities. Fourier transform infrared spectroscopy (FTIR) spectra of the new materials show the characteristic bands of the PVA alone and a modification of the band at around 1138 cm-1 and 1083 cm-1, showing an influence of the anthocyanins' addition on the sequence with crystalline and amorphous structures of the starting materials, as also shown by the results of the mechanical tests. These last showed an increase in thickening (from 29.92 µm to approx. 37 µm) and hydrophobicity with the concomitant increase in the added anthocyanins (change in wettability with water from 14° to 31°), decreasing the poor water/moisture resistance of PVA that decreases its strength and limits its application in food packaging, which makes the new materials ideal candidates for biodegradable packaging to extend the shelf-life of food. The functionalization also determines an increase in the opacity, from 2.46 to 3.42 T%/mm, the acquisition of antioxidant activity against 2,2-diphenyl-1-picrylhdrazyl and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals and, in the ferric reducing power assay, the antimicrobial (bactericidal) activity against different Staphylococcus aureus strains at the maximum tested concentration (1.00% of anthocyanins). On the whole, functionalization with anthocyanins results in the acquisition of new properties, making it suitable for food packaging purposes, as highlighted by a food fresh-keeping test.
Assuntos
Antocianinas , Antioxidantes , Embalagem de Alimentos , Álcool de Polivinil , Antocianinas/química , Antocianinas/farmacologia , Álcool de Polivinil/química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/síntese química , Embalagem de Alimentos/métodos , Espectroscopia de Infravermelho com Transformada de Fourier , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/químicaRESUMO
Within class II bacteriocins, we assume the presence of a separate subfamily of antimicrobial peptides possessing a broad spectrum of antimicrobial activity. Although these peptides are structurally related to the subclass IIa (pediocin-like) bacteriocins, they have significant differences in biological activities and, probably, a mechanism of their antimicrobial action. A representative of this subfamily is acidocin A from Lactobacillus acidophilus TK9201. We discovered the similarity between acidocin A and acidocin 8912 from Lactobacillus acidophilus TK8912 when analyzing plasmids from lactic acid bacteria and suggested the presence of a single evolutionary predecessor of these peptides. We obtained the C-terminally extended homolog of acidocin 8912, named acidocin 8912A, a possible intermediate form in the evolution of the former. The study of secondary structures and biological activities of these peptides showed their structural similarity to acidocin A; however, the antimicrobial activities of acidocin 8912 and acidocin 8912A were lower than that of acidocin A. In addition, these peptides demonstrated stronger cytotoxic and membranotropic effects. Building upon what we previously discovered about the immunomodulatory properties of acidocin A, we studied its proteolytic stability under conditions simulating those in the digestive tract and also assessed its ability to permeate intestinal epithelium using the Caco-2 cells monolayer model. In addition, we found a pronounced effect of acidocin A against fungi of the genus Candida, which might also expand the therapeutic potential of this bacterial antimicrobial peptide.
Assuntos
Bacteriocinas , Lactobacillus acidophilus , Bacteriocinas/química , Bacteriocinas/farmacologia , Bacteriocinas/genética , Humanos , Lactobacillus acidophilus/efeitos dos fármacos , Sequência de Aminoácidos , Células CACO-2 , Testes de Sensibilidade Microbiana , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Hemólise/efeitos dos fármacos , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/farmacologia , Estrutura Secundária de Proteína , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Cinnamaldehyde (CIN), a harmless bioactive chemical, is used in bio-based packaging films for its antibacterial and antioxidant properties. However, high amounts can change food flavor and odor. Thus, ZnO nanoparticles (NPs) as a supplementary antimicrobial agent are added to gelatin film with CIN. The CIN/ZnO interactions are the main topic of this investigation. FTIR-Attenuated Total Reflection (ATR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) were utilized to investigate CIN/ZnO@gelatin films. Transmission electron microscope (TEM) images revealed nanospheres morphology of ZnO NPs, with particle sizes ranging from 12 to 22 nm. ZnO NPs integration increased the overall activation energy of CIN/ZnO@gelatin by 11.94%. The incorporation of ZnO NPs into the CIN@gelatin film significantly reduced water vapour permeability (WVP) of the CIN/ZnO@gelatin film by 12.07% and the oxygen permeability (OP) by 86.86%. The water sorption isotherms of CIN/ZnO@gelatin were described using Guggenheim-Anderson-de Boer (GAB) model. The incorporation of ZnO NPs into the CIN@gelatin film reduced monolayer moisture content (M0) by 35.79% and significantly decreased the solubility of CIN/ZnO@gelatin by 15.15%. The inclusion of ZnO into CIN@gelatin film significantly decreased tensile strength of CIN/ZnO@gelatin by 13.32% and Young`s modulus by 18.33% and enhanced elongation at break by 11.27%. The incorporation of ZnO NPs into the CIN@gelatin film caused a significant decrease of antioxidant activity of CIN/ZnO@gelatin film by 9.09%. The most susceptible organisms to the CIN/ZnO@gelatin film included Candida albicans, Helicobacter pylori, and Micrococcus leutus. The inhibition zone produced by the CIN/ZnO@gelatin film versus Micrococcus leutus was 25.0 mm, which was comparable to the inhibition zone created by antibacterial gentamicin (23.33 mm) and cell viability assessment revealed that ZnO/CIN@gelatin (96.8 ± 0.1%) showed great performance as potent biocompatible active packaging material.
Assuntos
Acroleína , Embalagem de Alimentos , Gelatina , Óxido de Zinco , Acroleína/análogos & derivados , Acroleína/química , Acroleína/farmacologia , Gelatina/química , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Embalagem de Alimentos/métodos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Nanopartículas/química , Permeabilidade , Testes de Sensibilidade Microbiana , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Difração de Raios XRESUMO
BACKGROUND: Glioblastoma, a malignant tumor, has no curative treatment. Mitochondria have been reported to be involved in tumorigenesis and drug resistance in various cancers. Recently, mitochondria have been considered a potential target for treating glioblastoma. We are developing a new treatment for glioblastoma targeting mitochondria. The microenvironment of glioblastoma is reported to be a low-nutrition and hypoxic condition. We focused our research on how mitochondria work under tumor circumstances. METHODS: In this research, we used cell lines including U87, LN229, U373, T98G, and two patient-derived stem-like cells. First, we investigated the efficacy of mitochondria-targeted glioblastoma therapy in cell lines under glucose-starved conditions and the mechanism of cell death caused by mitochondria-targeted therapy. Second, we developed a treatment effective for cells with more glucose, because we believe that there is some lesion with higher glucose concentration in the tumor considering the heterogeneity of the tumor. RESULTS: We discovered that under glucose-starved conditions, mitochondria-related proteins and oxidative phosphorylation activity increased in glioblastoma cells, and in this condition, glioblastoma cells strongly depended on mitochondria. Administration of agents causing mitochondrial dysfunction including chloramphenicol was very effective and it led to cell death. The mechanism of cell death was not apoptosis but ferroptosis which is a recently discovered type of cell death caused by iron accumulation. In normoglycemic conditions, the effect of chloramphenicol was poor for the short term, however, for the long term, it was effective and caused cell death. Although both chloramphenicol alone and combined treatment using 2-DG (glycolysis inhibitor) and chloramphenicol had poor effects on cells in glucose-sufficient conditions, combined treatment was very effective for the short term under normal glucose conditions. These results suggest the importance of controlling glucose concentration. The effect of combined treatment was also confirmed in hypoxic conditions and for patient-derived neurosphere cells. And the mechanism of cell death was ferroptosis, too. CONCLUSIONS: Our mitochondria-targeted treatment was effective for cells with both glucose-starved conditions and normoglycemic conditions. It is necessary to investigate its effectiveness in vivo in the future. However, chloramphenicol has already been used, and therefore, this treatment can be used for humans safely. This discovery is expected to make a major contribution to the development of treatments for glioblastomas.
Assuntos
Ferroptose , Glioblastoma , Mitocôndrias , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ferroptose/efeitos dos fármacos , Linhagem Celular Tumoral , Anti-Infecciosos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Proliferação de Células/efeitos dos fármacosRESUMO
OBJECTIVE: To develop a novel calcium silver zeolite (Ca-Ag-Zeo) and assess its biocompatibility, physiochemical properties and antimicrobial effects. METHODS: Ca-Ag-Zeo was synthesized using ion-exchange method with calcium chloride, silver nitrate and Zeolite X (Zeo). Silver zeolite X (Ag-Zeo) and Zeo were set as control. The chemical structure, morphology, crystal structure and elemental composition of Ca-Ag-Zeo was characterized by X-ray diffraction spectrum, scanning electron microscopy, transmission electron microscopy and energy dispersive spectroscopy, respectively. Its biocompatibility on the human gingival fibroblasts was assessed by cell counting kit-8 assay. Its physiochemical properties were determined by the released calcium and silver ion using Inductive Coupled Plasma Emission Spectrometry for up to 12 weeks. The antimicrobial properties on Streptococcus mutans, Lactobacillus acidophilus, Lactobacillus casei, and Candida albicans were assessed by minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC) assay. RESULTS: Ca-Ag-Zeo with a hexagonal cage structure was synthesized. As for biocompatibility, the half-maximal inhibitory concentration (± SD in mg/mL) of Ca-Ag-Zeo, Ag-Zeo and Zeo in human gingival fibroblasts were 0.52 ± 0.05, 0.15 ± 0.01 and 3.35 ± 0.58, respectively (Zeo > Ca-Ag-Zeo > Ag-Zeo; p < 0.05). As for physiochemical properties, the accumulated ion release (± SD in mg) of Ca-Ag-Zeo, Ag-Zeo and Zeo were 0.011 ± 0.003, 0 and 0 for calcium ion, respectively (Ca-Ag-Zeo > Ag-Zeo, Zeo; p < 0.001), and 0.213 ± 0.032, 0.209 ± 0.019 and 0 for silver ion, respectively (Ca-Ag-Zeo, Ag-Zeo > Zeo; p < 0.001). As for anti-microbial ability, the MBC/MFC (mg/mL) of Ca-Ag-Zeo, Ag-Zeo and Zeo were 32, 16 and > 256 against Streptococcus mutans; 32, 16, > 256 against Lactobacillus acidophilus; 16, 16, and 256 against Lactobacillus casei; 0.25, 0.125; and 2, 1, > 256 against Candida albicans, respectively. CONCLUSION: A novel Ca-Ag-Zeo was developed. It presented better biocompatibility compared to Ag-Zeo. It released calcium and silver ions sustainably, and it could inhibit the growth of common cariogenic microorganisms.
Assuntos
Cálcio , Candida albicans , Cárie Dentária , Fibroblastos , Testes de Sensibilidade Microbiana , Prata , Streptococcus mutans , Zeolitas , Humanos , Zeolitas/farmacologia , Zeolitas/química , Streptococcus mutans/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Cárie Dentária/prevenção & controle , Cárie Dentária/microbiologia , Prata/farmacologia , Prata/química , Lactobacillus acidophilus/efeitos dos fármacos , Difração de Raios X , Gengiva/efeitos dos fármacos , Gengiva/citologia , Lacticaseibacillus casei/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Materiais Biocompatíveis/farmacologia , Microscopia Eletrônica de Transmissão , Teste de Materiais , Nitrato de Prata/farmacologia , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologiaRESUMO
The newly recorded Phyllymenia gibesii in the Mediterranean Sea at Alexandria coast of Egypt is regarded as a significant source of bioactive substances and is applied as an antioxidant, anti-inflammatory, and antimicrobial agent. According to the HPLC chromatograms, the acetone extract of P. gibesii comprised ten photosynthetic pigments (chlorophyll-a, chlorophyll-d, α-carotene, ß-carotene, phycocyanin, allophycocyanin, antheraxanthin, ß-cryptoxanthin, lutein, and violaxanthin). Total carotenoids were the dominant class in the pigments' profile, achieving a concentration of 257 g/g dry weight. The P. gibbesii extract had a total content of phenols (146.67 mg/g) and a total content of flavonoids (104.40 mg/g). The capacity of all the investigated biological activities augmented with the concentration of the algal extract. The maximal DPPH scavenging capacity was 81.44%, with an inhibitory concentration (IC50) of 9.88 µg/mL. Additionally, the highest ABTS scavenging capacity was 89.62%, recording an IC50 of 21.77 µg/mL. The hemolytic activity of P. gibbesii attained a maximum capacity of 49.88% with an IC50 of 100.25 µg/mL. Data also showed the maximum anti-inflammatory effectiveness at 81.25%, with an IC50 of 99.75 µg/mL. Furthermore, the extract exhibited antimicrobial capacity against all reference strains, particularly at high concentrations (0.1 mg/mL), with the greatest effect on C. albicans and E. coli.
Assuntos
Polifenóis , Polifenóis/farmacologia , Polifenóis/química , Antioxidantes/farmacologia , Antioxidantes/química , Pigmentos Biológicos/química , Pigmentos Biológicos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Estramenópilas/química , Mar Mediterrâneo , Cromatografia Líquida de Alta Pressão , Testes de Sensibilidade MicrobianaRESUMO
Sulfur-containing compounds have diverse biological functions and are crucial in crop protection chemistry. In this study, a series of novel 1-methyl-1H-pyrazol-5-amine derivatives incorporating disulfide moieties were synthesized and evaluated for their antimicrobial properties. In vitro bioassays demonstrated that compound 7f displayed potent antifungal activity against Valsa mali, with an EC50 value of 0.64 mg/L, outperforming allicin (EC50 = 26.0 mg/L) but lower than tebuconazole (EC50 = 0.33 mg/L). In vivo experiments confirmed that compound 7f could effectively inhibit V. mali infection on apples at a concentration of 100 mg/L, similar to the positive control tebuconazole. Mechanistic studies revealed that compound 7f could induce hyphal shrinkage and collapse, trigger intracellular reactive oxygen species accumulation, modulate antioxidant enzyme activities, initiate lipid peroxidation, and ultimately cause irreversible oxidative damage to the cells of V. mali. Additionally, compound 7b exhibited notable antibacterial activity, particularly against Pseudomonas syringae pv. actinidiae, with a MIC90 value of 1.56 mg/L, surpassing the positive controls allicin, bismerthiazol, and streptomycin sulfate. These findings suggest that 1-methyl-1H-pyrazol-5-amine derivatives containing disulfide moieties hold promise as potent candidates for the development of novel antimicrobial agents.