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A ansiedade desempenha um papel significativo na experiência de tratamentos odontológicos e pode resultar em evasão por parte dos pacientes. Isso é especialmente relevante para grupos como pacientes pediátricos e aqueles com necessidades especiais, que muitas vezes requerem técnicas de controle de comportamento ou sedação devido à ansiedade. No entanto, a ansiedade não deve ser negligenciada mesmo em pacientes sem odontofobia grave, pois está relacionada à percepção da dor durante os procedimentos odontológicos. A sedação consciente com óxido nitroso surge como uma alternativa valiosa para reduzir a ansiedade e melhorar o conforto do paciente. Ao contrário dos benzodiazepínicos e da anestesia geral, o óxido nitroso atua no sistema nervoso de uma forma que deprime levemente o córtex cerebral, sem afetar o centro respiratório. Isso permite o uso de concentrações subanestésicas do gás, administradas com oxigênio por meio de uma máscara nasal. O óxido nitroso é de rápida ação, pouco solúvel e tem um período de recuperação breve, permitindo que os pacientes retornem rapidamente às atividades normais. Este estudo, uma revisão de literatura, explora o mecanismo de ação do óxido nitroso, suas indicações na prática odontológica e examina possíveis riscos e contraindicações associados ao seu uso. Em resumo, a sedação consciente com óxido nitroso se mostra como uma opção promissora para aliviar a ansiedade e melhorar a experiência de tratamentos odontológicos, beneficiando uma ampla gama de pacientes, não apenas aqueles com fobias graves.
Anxiety, in an outpatient dental environment, plays a fundamental role in pain and discomfort expectation, resulting in increase of treatment evasion. The groups that present greater difficulty in cooperation are children and special needs patients, with behavioral control and sedation being often necessary. Nevertheless, literature emphasizes that anxiety must be evaluated as a critical stage and its management done not only in patients with elevated anxiety levels, but being crucial on pain control of every dental patient, since higher grades of restlessness equals higher pain perception. It is known that the use of nitrous oxide in conscious sedation proves to be an useful tool on reducing anxiety and enabling comfortable interventions, indicating that it is an alternative to the use of benzodiazepines and general anesthesia. The drug acts on the nervous system, promoting a slight depression of the cerebral cortex and, unlike benzodiazepines, which act at the medulla level, it does not depress the respiratory center. The technique uses sub-anesthetic concentrations of nitrous oxide delivered with oxygen through a nasal mask. Nitrous oxide is poorly soluble and has a rapid onset of action, being therefore associated with a rapid recovery period. The duration of sedation is controlled and the patient can quickly return to normal activities. This paper is a narrative review with the objective of exploring the mechanism of action of this gas, evaluating its indications for use in dental clinic and verifying possible risks and contraindications.
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Sedação Consciente , Ansiedade ao Tratamento Odontológico , Clínicas Odontológicas , Analgesia , Óxido NitrosoRESUMO
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by selective dopaminergic loss. Non dopaminergic neurotransmitters such as glutamate are also involved in PD progression. NMDA receptor/postsynaptic density protein 95 (PSD-95)/neuronal nitric oxide synthase (nNOS) activation is involved in neuronal excitability in PD. Here, we are focusing on the evaluating these post-synaptic protein levels in the 6-OHDA model of PD. Adult male C57BL/6 mice subjected to unilateral striatal injury with 6-OHDA were assessed at 1-, 2-, or 4-weeks post-lesion. Animals were subjected to an apomorphine-induced rotation test followed by the analysis of protein content, synaptic structure, and NOx production. All biochemical analysis was performed comparing the control versus lesioned sides of the same animal. 6-OHDA mice exhibited contralateral rotation activity, difficulties in coordinating movements, and changes in Iba-1 and glial fibrillary acidic protein (GFAP) expression during the whole period. At one week of survival, the mice showed a shift in NMDA composition, favoring the GluN2A subunit and increased PSD95 and nNOS expression and NOx formation. After two-weeks, a decrease in the total number of synapses was observed in the lesioned side. However, the number of excitatory synapses was increased with a higher content of GluN1 subunit and PSD95. After four weeks, NMDA receptor subunits restored to control levels. Interestingly, NOx formation in the serum increased. This study reveals, for the first time, the temporal course of behavioral deficits and glutamatergic synaptic plasticity through NMDAr subunit shift. Together, these data demonstrate that dopamine depletion leads to a fine adaptive response over time, which can be used for further studies of therapeutic management adjustments with the progression of PD.
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Copper oxide nanoparticles (CuONPs) have been produced on a large scale because they can be applied across various fields, especially in nano-enabled healthcare and agricultural products. However, the increasing use of CuONPs leads to their release and accumulation into the environment. The CuONPs uptaken by seeds and their implications on germination behavior have been reported, but little is known or understood about their impact on photosynthesis in seed tissues. To fill knowledge gaps, this study evaluated the effects of CuONP concentrations (0-300 mg L-1) on the photosynthetic activity of Inga laurina seeds. The microscopy data showed that CuONPs had an average size distribution of 57.5 ± 0.7 nm. Copper ion release and production of reactive oxygen species (ROS) by CuONPs were also evaluated by dialysis and spectroscopy experiments, respectively. CuONPs were not able to intrinsically generate ROS and released a low content of Cu2⺠ions (4.5%, w/w). Time evolution of chlorophyll fluorescence imaging and laser-induced fluorescence spectroscopy were used to monitor the seeds subjected to nanoparticles during 168 h. The data demonstrate that CuONPs affected the steady-state maximum chlorophyll fluorescence ( F m ' ), the photochemical efficiency of photosystem II ( F v / F m ), and non-photochemical quenching ( NPQ ) of Inga laurina seeds over time. Besides, the NPQ significantly increased at the seed development stage, near the root protrusion stage, probably due to energy dissipation at this germination step. Additionally, the results indicated that CuONPs can change the oscillatory rhythms of energy dissipation of the seeds, disturbing the circadian clock. In conclusion, the results indicate that CuONPs can affect the photosynthetic behavior of I. laurina seeds. These findings open opportunities for using chlorophyll fluorescence as a non-destructive tool to evaluate nanoparticle impact on photosynthetic activity in seed tissues.
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Cobre , Fabaceae , Fotossíntese , Sementes , Fotossíntese/efeitos dos fármacos , Sementes/efeitos dos fármacos , Fabaceae/efeitos dos fármacos , Germinação/efeitos dos fármacos , Nanopartículas , Clorofila/metabolismoRESUMO
Patients with sickle cell disease (SCD) display an overactive bladder (OAB). Intravascular hemolysis in SCD is associated with various severe SCD complications. However, no experimental studies have evaluated the effect of intravascular hemolysis on bladder function. This study aimed to assess the effects of intravascular hemolysis on the micturition process and the contractile mechanisms of the detrusor smooth muscle (DSM) in a mouse model with phenylhydrazine (PHZ)-induced hemolysis; furthermore, it aimed to investigate the role of intravascular hemolysis in the dysfunction of nitric oxide (NO) signaling and in increasing oxidative stress in the bladder. Mice underwent a void spot assay, and DSM contractions were evaluated in organ baths. The PHZ group exhibited increased urinary frequency and increased void volumes. DSM contractile responses to carbachol, KCl, α-ß-methylene-ATP, and EFS were increased in the PHZ group. Protein expression of phosphorylated endothelial NO synthase (eNOS) (Ser-1177), phosphorylated neuronal NO synthase (nNOS) (Ser-1417), and phosphorylated vasodilator-stimulated phosphoprotein (VASP) (Ser-239) decreased in the bladder of the PHZ group. Protein expression of oxidative stress markers, NOX-2, 3-NT, and 4-HNE, increased in the bladder of the PHZ group. Our study shows that intravascular hemolysis promotes voiding dysfunction correlated with alterations in the NO signaling pathway in the bladder, as evidenced by reduced levels of p-eNOS (Ser-1177), nNOS (Ser-1417), and p-VASP (Ser-239). The study also showed that intravascular hemolysis increases oxidative stress in the bladder. Our study indicates that intravascular hemolysis promotes an OAB phenotype similar to those observed in patients and mice with SCD.
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This study reports on the modification of bacterial cellulose (BC) membranes produced by static fermentation of Komagataeibacter xylinus bacterial strains with graphene oxide-silver nanoparticles (GO-Ag) to yield skin wound dressings with improved antibacterial properties. The GO-Ag sheets were synthesized through chemical reduction with sodium citrate and were utilized to functionalize the BC membranes (BC/GO-Ag). The BC/GO-Ag composites were characterized to determine their surface charge, morphology, exudate absorption, antimicrobial activity, and cytotoxicity by using fibroblast cells. The antimicrobial activity of the wound dressings was assessed against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The results indicate that the BC/GO-Ag dressings can inhibit â¼70% of E. coli cells. Our findings also revealed that the porous BC/GO-Ag antimicrobial dressings can efficiently retain 94% of exudate absorption after exposure to simulated body fluid (SBF) for 24 h. These results suggest that the dressings could absorb excess exudate from the wound during clinical application, maintaining adequate moisture, and promoting the proliferation of epithelial cells. The BC/GO-Ag hybrid materials exhibited excellent mechanical flexibility and low cytotoxicity to fibroblast cells, making excellent wound dressings able to control bacterial infectious processes and promote the fast healing of dermal lesions.
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Antibacterianos , Materiais Biocompatíveis , Celulose , Escherichia coli , Grafite , Teste de Materiais , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Prata , Staphylococcus aureus , Cicatrização , Grafite/química , Grafite/farmacologia , Prata/química , Prata/farmacologia , Cicatrização/efeitos dos fármacos , Celulose/química , Celulose/farmacologia , Nanopartículas Metálicas/química , Antibacterianos/química , Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Tamanho da Partícula , Pseudomonas aeruginosa/efeitos dos fármacos , Gluconacetobacter xylinus/química , Humanos , Camundongos , Bandagens , AnimaisRESUMO
OBJECTIVE: The aim of this study was to evaluate the effect of an adhesive loaded with 0.2 % copper (Cu) and 5 % zinc oxide (ZnO) nanoparticles (Nps) on its adhesive properties and enzymatic activity at the hybrid layer ex vivo in a randomized clinical model. METHODS: Fifteen patients participated in this study, and a total of 30 third molars were used. Occlusal cavities (4 × 4 × 2 mm) were made in each tooth, and randomly divided into 2 groups: (i) Experimental group: commercial adhesive loaded with 0.2wt % CuNps and 5wt % ZnONps; and (ii) Control Group: non-loaded commercial adhesive. Teeth were restored with resin composite. Thirty days later, extractions were performed. Extracted teeth were longitudinally sectioned. Nps in powder were characterized by field emission scanning electron microscope (FE-SEM) and energy dispersive X-ray (EDX) analysis. Microtensile bond strength (µTBS), degree of conversion (DC), and nanoleakeage (NL) tests were executed. In situ zymography (Zym) was performed to evaluate the gelatinolytic activity at the hybrid layer. Student's t-test (α = 0.05) was applied for all tests. RESULTS: µTBS and DC did not show significant differences (p > 0.05) between both groups. However, NL and gelatinolytic activity at the hybrid layer showed significant values (p < 0.05) for experimental group in comparison with control group. CONCLUSION: The addition of 0.2 % CuNps and 5 % ZnONps to a universal adhesive decreases NL and gelatinolytic activity at the hybrid layer, without jeopardizing its adhesive properties. SIGNIFICANCE: This randomized clinical trial with ex vivo analysis demonstrate that a commercial adhesive modified with 0.2wt % Cu and 5wt % ZnO Nps that does not affect its adhesive properties, reducing gelatinolytic activity and nanoleakage at the hybrid layer, which should contribute to an improvement of long term bonding-dentine clinical performance.
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Resinas Compostas , Cobre , Colagem Dentária , Microscopia Eletrônica de Varredura , Resistência à Tração , Óxido de Zinco , Humanos , Óxido de Zinco/química , Cobre/química , Colagem Dentária/métodos , Resinas Compostas/química , Nanopartículas/química , Adesivos Dentinários/química , Dentina/efeitos dos fármacos , Dentina/enzimologia , Teste de Materiais , Masculino , Cimentos de Resina/química , Adulto , Feminino , Propriedades de Superfície , Cimentos Dentários/química , Dente Serotino , Restauração Dentária Permanente/métodos , Espectrometria por Raios XRESUMO
The renin-angiotensin system (RAS) is composed of a series of peptides, receptors, and enzymes that play a pivotal role in maintaining cardiovascular homeostasis. Among the most important players in this system are the angiotensin-II and angiotensin-(1-7) peptides. Our group has recently demonstrated that alamandine (ALA), a peptide with structural and functional similarities to angiotensin-(1-7), interacts with cardiomyocytes, enhancing contractility via the Mas-related G protein-coupled receptor member D (MrgD). It is currently unknown whether this modulation varies along the distinct phases of the day. To address this issue, we assessed the ALA-induced contractility response of cardiomyocytes from mice at four Zeitgeber times (ZTs). At ZT2 (light phase), ALA enhanced cardiomyocyte shortening in an MrgD receptor-dependent manner, which was associated with nitric oxide (NO) production. At ZT14 (dark phase), ALA induced a negative modulation on the cardiomyocyte contraction. ß-Alanine, an MrgD agonist, reproduced the time-of-day effects of ALA on myocyte shortening. NG-nitro-l-arginine methyl ester, an NO synthase inhibitor, blocked the increase in fractional shortening induced by ALA at ZT2. No effect of ALA on myocyte shortening was observed at ZT8 and ZT20. Our results show that ALA/MrgD signaling in cardiomyocytes is subject to temporal modulation. This finding has significant implications for pharmacological approaches that combine chronotherapy for cardiac conditions triggered by disruption of circadian rhythms and hormonal signaling.NEW & NOTEWORTHY Alamandine, a member of the renin-angiotensin system, serves critical roles in cardioprotection, including the modulation of cardiomyocyte contractility. Whether this effect varies along the day is unknown. Our results provide evidence that alamandine via receptor MrgD exerts opposing actions on cardiomyocyte shortening, enhancing, or reducing contraction depending on the time of day. These findings may have significant implications for the development and effectiveness of future cardiac therapies.
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Contração Miocárdica , Miócitos Cardíacos , Óxido Nítrico , Oligopeptídeos , Receptores Acoplados a Proteínas G , Animais , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Camundongos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Óxido Nítrico/metabolismo , Oligopeptídeos/farmacologia , Camundongos Endogâmicos C57BL , Ritmo Circadiano/fisiologia , Ritmo Circadiano/efeitos dos fármacos , Receptores de Neuropeptídeos/metabolismo , Receptores de Neuropeptídeos/agonistas , Receptores de Neuropeptídeos/antagonistas & inibidores , Masculino , Células Cultivadas , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologiaRESUMO
Mammalian and reptilian vascular tissues present basal release of 6-nitrodopamine, which is reduced when the tissues are pre-incubated with the NO synthase inhibitor L-NG-Nitro arginine methyl ester (L-NAME), or when the endothelium is mechanically removed. 6-Nitrodopamine induces vasorelaxation in pre-contracted vascular rings by antagonizing the dopaminergic D2-like receptor. Here it was investigated whether male swine vessels (including carotid, left descendent coronary, renal, and femoral arteries) release 6-nitrodopamine, dopamine, noradrenaline, and adrenaline, as measured by liquid chromatography coupled to tandem mass spectrometry. The in vitro vasorelaxant action of 6-nitrodopamine was evaluated in carotid, coronary, renal, and femoral arteries precontracted by U-46619 (3 nM), and compared to that induced by the dopamine D2-receptor antagonist L-741,626. Expression of tyrosine hydroxylase and the neuromaker calretinin was investigated by immunohistochemistry. All vascular tissues presented basal release of endothelium-derived catecholamines. The relaxation induced by 6-nitrodopamine was not affected by preincubation of the tissues with either L-NAME (100 µM, 30-min preincubation) or the heme-site inhibitor of soluble guanylyl cyclase ODQ (100 µM, 30-min preincubation). Electrical field stimulation (EFS)-induced contractions were significantly potentiated by previous incubation with L-NAME, but unaffected by ODQ preincubation. The contractions induced by EFS were reduced by preincubation with either 6-nitrodopamine or L-741,626. Immunohistochemistry in all arteries revealed the presence of tyrosine hydroxylase in the endothelium, whereas immunoreactivity for calretinin was negative. Swine vessels present basal release of endothelium-derived catecholamines and expression of tyrosine hydroxylase in the endothelium. The vasodilation induced by 6-nitrodopamine is due to blockade of dopaminergic D2-like receptors.
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Vasodilatação , Animais , Masculino , Vasodilatação/efeitos dos fármacos , Suínos , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/metabolismo , Artéria Femoral/fisiologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiologia , Vasos Coronários/metabolismo , Artéria Renal/efeitos dos fármacos , Artéria Renal/metabolismo , Artéria Renal/fisiologia , Dopamina/metabolismo , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/metabolismo , Artérias Carótidas/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Vasodilatadores/farmacologiaRESUMO
Hearing loss (HL) affects more than 5% of the global population, with projections indicating an impact of up to 50% on young individuals in the next years. HL treatments remain limited due to the inner ear's hermeticism. HL often involves inflammatory processes, underscoring the need for enhanced delivery of antiinflammatory agents to the inner ear. Our research focuses on the development of a directed therapy based on magnetic nanoparticles (MNPs). We previously synthesized biocompatible folic acid-coated iron oxide-core nanoparticles (MNPs@FA) as potential carriers for the anti-inflammatory Diclofenac (Dfc). This study aims to incorporate Dfc onto MNPs@FA to facilitate targeted drug delivery to the inner ear. Through optimizing the loading procedure, we achieved optimal loading capacity. Dfc release was studied in the simulated target fluid and the administration vehicle. Complete characterization is also shown. In vitro biocompatibility testing ensured the biosafety of the resulting formulation. Subsequent ex vivo targeting assays on murine cochleae validated the nanosystems' ability to penetrate the round window membrane, one of the main HL therapy barriers. These findings serve as validation before continuing to more complex in vivo studies. Together, the data here presented represent an advancement in addressing unmet medical needs in HL therapy.
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Scaffolds for the filling and regeneration of osteochondral defects are a current challenge in the biomaterials field, and solutions with greater functionality are still being sought. The novel approach of this work was to obtain scaffolds with biologically active additives possessing microstructural, permeability, and mechanical properties, mimicking the complexity of natural cartilage. Four types of scaffolds with a gelatin/alginate matrix modified with hydroxyapatite were obtained, and the relationship between the modifiers and substrate properties was evaluated. They differed in the type of second modifier used, which was hydrated MgCl2 in two proportions, ZnO, and nanohydroxyapatite. The samples were obtained by freeze-drying by using two-stage freezing. Based on microstructural observations combined with X-ray microanalysis, the microstructure of the samples and the elemental content were assessed. Permeability and mechanical tests were also performed. The scaffolds exhibited a network of interconnected pores and complex microarchitecture, with lower porosity at the surface (15 ± 7 to 29 ± 6%) and higher porosity at the center (67 ± 8 to 75 ± 8%). The additives had varying effects on the pore sizes and permeabilities of the samples. ZnO yielded the most permeable scaffolds (5.92 × 10-11 m2), whereas nanohydroxyapatite yielded the scaffold with the lowest permeability (1.18 × 10-11 m2), values within the range reported for trabecular bone. The magnesium content had no statistically significant effect on the permeability. The best mechanical parameters were obtained for ZnO samples and those containing hydrated MgCl2. The scaffold's properties meet the criteria for filling osteochondral defects. The developed scaffolds follow a biomimetic approach in terms of hierarchical microarchitecture and mechanical parameters as well as chemical composition. The obtained composite materials have the potential as biomimetic scaffolds for the regeneration of osteochondral defects.
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Hidrogéis , Cloreto de Magnésio , Alicerces Teciduais , Óxido de Zinco , Óxido de Zinco/química , Alicerces Teciduais/química , Cloreto de Magnésio/química , Hidrogéis/química , Porosidade , Alginatos/química , Durapatita/química , Permeabilidade , Gelatina/química , Teste de MateriaisRESUMO
BACKGROUND: The role of nitric oxide (NO) in plant stress tolerance, as well as in increasing post-harvest quality, has been extensively demonstrated in several fruits and vegetable crops; however, the effects of its pre-harvest application on post-harvest quality are still poorly documented. Therefore, the pre-harvest application of NO in red beet (Beta vulgaris subsp. vulgaris) plants cultivated under well-watered and drought conditions was evaluated to assess whether it improves the post-harvest quality of their storage roots. Red beet plants cultivated under well-watered (80% of water holding capacity) or drought condition (15% of water holding capacity) were sprayed weekly with water (control) or 100 µmol L-1 sodium nitroprusside (SNP), an NO donor. Sixty-six days after sowing, red beet roots were harvested, and root yield, total sugar yield, reducing sugars, non-reducing sugars, proteins, lipids, root ashes, root moisture, soluble solids, titratable acidity, pH, vitamin C, total phenolics, total betalains, betacyanins, betaxanthins and antioxidant capacity were determined. RESULTS: While drought led to a reduction in root yield, sugars, lipids and titratable acidity, it increased phenolic compounds, betalains and the antioxidant capacity of beets. SNP reversed the negative effects of drought on sugar, lipid and organic acid contents and increased antioxidant capacity independent of stress. CONCLUSION: Pre-harvest SNP treatment reversed drought-induced yield reductions in beets, while boosting bioactive compounds and antioxidant capacity. It also enhanced vitamin C content independently, indicating its dual role in stress mitigation and beet quality improvement. Future research should explore other crops and stress conditions. © 2024 Society of Chemical Industry.
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Bone tissue engineering is a promising alternative to repair wounds caused by cellular or physical accidents that humans face daily. In this sense, the search for new graphene oxide (GO) nanofillers related to their degree of oxidation is born as an alternative bioactive component in forming new scaffolds. In the present study, three different GOs were synthesized with varying degrees of oxidation and studied chemically and tissue-wise. The oxidation degree was determined through infrared (FTIR), X-ray diffraction (XRD), X-ray photoelectron (XPS), and Raman spectroscopy (RS). The morphology of the samples was analyzed using scanning electron microscopy (SEM). The oxygen content was deeply described using the deconvolution of RS and XPS techniques. The latter represents the oxidation degree for each of the samples and the formation of new bonds promoted by the graphitization of the material. In the RS, two characteristic bands were observed according to the degree of oxidation and the degree of graphitization of the material represented in bands D and G with different relative intensities, suggesting that the samples have different crystallite sizes. This size was described using the Tuinstra-Koenig model, ranging between 18.7 and 25.1 nm. Finally, the bone neoformation observed in the cranial defects of critical size indicates that the F1 and F2 samples, besides being compatible and resorbable, acted as a bridge for bone healing through regeneration. This promoted healing by restoring bone and tissue structure without triggering a strong immune response.
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Regeneração Óssea , Grafite , Engenharia Tecidual , Alicerces Teciduais , Grafite/química , Regeneração Óssea/efeitos dos fármacos , Engenharia Tecidual/métodos , Animais , Alicerces Teciduais/química , Nanoestruturas/química , Osso e Ossos/efeitos dos fármacos , Análise Espectral Raman , Oxirredução , Difração de Raios X , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Ratos , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Leishmaniasis is a group of infectious diseases transmitted to humans during vector bites and caused by protozoans of the genus Leishmania. Conventional therapies face challenges due to their serious side effects, prompting research into new anti-leishmania agents. In this context, we investigated the effectiveness of morolic acid, a pentacyclic triterpene, on L. amazonensis promastigotes and amastigotes. The present study employed the MTT assay, cytokine analysis using optEIATM kits, an H2DCFDA test, and nitric oxide dosage involving nitrite production and Griess reagent. Morolic acid inhibited promastigote and axenic amastigote growth forms at IC50 values of 1.13 µM and 2.74 µM, respectively. For cytotoxicity to macrophages and VERO cells, morolic acid obtained respective CC50 values of 68.61 µM and 82.94 µM. The compound causes damage to the parasite membrane, leading to cellular leakage. In the infection assay, there was a decrease in parasite load, resulting in a CI50 of 2.56 µM. This effect was associated with immunomodulatory activity, altering macrophage structural and cellular parasite elimination mechanisms. Morolic acid proved to be an effective and selective natural compound, making it a strong candidate for future in vivo studies in cutaneous leishmaniasis.
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Core-shell micro/nanomotors have garnered significant interest in biomedicine owing to their versatile task-performing capabilities. However, their effectiveness for photothermal therapy (PTT) still faces challenges because of their poor tumor accumulation, lower light-to-heat conversion, and due to the limited penetration of near-infrared (NIR) light. In this study, we present a novel core-shell micromotor that combines magnetic and photothermal properties. It is synthesized via the template-assisted electrodeposition of iron (Fe) and reduced graphene oxide (rGO) on a microtubular pore-shaped membrane. The resulting Fe-rGO micromotor consists of a core of oval-shaped zero-valent iron nanoparticles with large magnetization. At the same time, the outer layer has a uniform reduced graphene oxide (rGO) topography. Combined, these Fe-rGO core-shell micromotors respond to magnetic forces and near-infrared (NIR) light (1064 nm), achieving a remarkable photothermal conversion efficiency of 78% at a concentration of 434 µg mL-1. They can also carry doxorubicin (DOX) and rapidly release it upon NIR irradiation. Additionally, preliminary results regarding the biocompatibility of these micromotors through in vitro tests on a 3D breast cancer model demonstrate low cytotoxicity and strong accumulation. These promising results suggest that such Fe-rGO core-shell micromotors could hold great potential for combined photothermal therapy.
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This research enhances ethanol sensing with Fe-doped tetragonal SnO2 films on glass, improving gas sensor reliability and sensitivity. The primary objective was to improve the sensitivity and operational efficiency of SnO2 sensors through Fe doping. The SnO2 sensors were synthesized using a flexible and adaptable method that allows for precise doping control, with energy-dispersive X-ray spectroscopy (EDX) confirming homogeneous Fe distribution within the SnO2 matrix. A morphological analysis showed a surface structure ideal for gas sensing. The results demonstrated significant improvement in ethanol response (1 to 20 ppm) and lower temperatures compared to undoped SnO2 sensors. The Fe-doped sensors exhibited higher sensitivity, enabling the detection of low ethanol concentrations and showing rapid response and recovery times. These findings suggest that Fe doping enhances the interaction between ethanol molecules and the sensor surface, improving performance. A mathematical model based on diffusion in porous media was employed to further analyze and optimize sensor performance. The model considers the diffusion of ethanol molecules through the porous SnO2 matrix, considering factors such as surface morphology and doping concentration. Additionally, the choice of electrode material plays a crucial role in extending the sensor's lifespan, highlighting the importance of material selection in sensor design.
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Campylobacter jejuni is a major cause of global foodborne illnesses. To develop alternative antimicrobial strategies against C. jejuni, this study designed and optimized the green synthesis of metallic nanoparticles (NPs) with intracellular components of the medicinal fungus Ganoderma sessile to provide the needed reducing and stabilizing agents. NPs were characterized by transmission electron microscopy and dynamic light scattering, and the quasi-spherical NPs had sizes of 2.9 ± 0.9 nm for the copper oxide NPs and 14.7 ± 0.6 nm for the silver NPs. Surface charge assessment revealed zeta potentials of -21.0 ± 6.5 mV and -24.4 ± 7.9 mV for the copper oxide and silver NPs, respectively. The growth inhibition of C. jejuni by the NPs occurred through attachment to the outer cell membrane and subsequent intracellular internalization and resulted in minimum inhibitory concentrations of the silver NPs at 6 µg/mL and copper oxide NPs at 10 µg/mL. On the other hand, a differential ROS production caused by silver and copper NPs was observed. In summary, this research presents the first demonstration of using green synthesis with the medicinal fungus G. sessile to produce metallic NPs that effectively inhibit C. jejuni growth, providing a sustainable and effective approach to the traditional use of antimicrobials.
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INTRODUCTION: Furoxan and benzofuroxan are compounds containing an N-oxide function, known for their diverse pharmacological properties, including antimicrobial and antiinflammatory effects. This study aimed to investigate these activities using an in-house library of N-oxide compounds. METHOD: Twenty compounds were tested against both Gram-positive and Gram-negative bacteria, including Cutibacterium acnes (C. acnes), a microorganism implicated in the development of acne vulgaris. One compound, (E)-4-(3-((2-(3-hydroxybenzoyl)hydrazone)methyl)phenoxy)-3- (phenylsulfonyl)-1,2,5-oxadiazol-2-N-oxide (compound 15), exhibited selective antimicrobial activity against C. acnes, with a Minimum Inhibitory Concentration (MIC) value of 2 µg/mL. Indirect measurement of Nitric Oxide (NO) release showed that compound 15 and isosorbide dinitrate, when treated with L-cysteine, produced nitrite levels of 20.1% and 9.95%, respectively. Using a NO scavenger (PTIO) in combination with compound 15 in a culture of C. acnes resulted in reduced antimicrobial activity, indicating that NO release is part of its mechanism of action. Cytotoxicity assessments using murine macrophages showed cellular viability above 70% at concentrations up to 0.78 µg/mL. RESULTS: Measurements of Interleukin-1 beta (IL1-ß) and Tumor Necrosis Factor-alpha (TNF-α) indicated that compound 15 did not reduce the levels of these pro-inflammatory cytokines. Sustained NO production by inducible Nitric Oxide Synthase (iNOS) in macrophages or neutrophils has been found to be involved in the inflammatory process in acne vulgaris and lead to toxicity in surrounding tissues. Nitrite levels in the supernatant of murine macrophages were found to be decreased at a concentration of 0.78 µg/mL of compound 15, indicating an anti-inflammatory effect. In vivo studies were conducted using Balb/c nude mice inoculated subcutaneously with C. acnes. Cream and gel formulations of compound 15 were applied to treat the animals, along with commercially available anti-acne drugs, for 14 days. Animals treated with a cream base containing 5% of compound 15 exhibited less acanthosis with mild inflammatory infiltration compared to other groups, highlighting its anti-inflammatory properties. CONCLUSION: Similar results were observed in the benzoyl peroxide group, demonstrating that compound 15 presented comparable anti-inflammatory activity to the FDA-approved drug. These promising results suggest that compound 15 has a dual mechanism of action, with selective antimicrobial activity against C. acnes and notable anti-inflammatory properties, making it a potential prototype for developing new treatments for acne vulgaris.
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Leishmaniasis, a critical Neglected Tropical Disease caused by Leishmania protozoa, represents a significant global health risk, particularly in resource-limited regions. Conventional treatments are effective but suffer from serious limitations, such as toxicity, prolonged treatment courses, and rising drug resistance. Herein, we highlight the potential of inorganic nanomaterials as an innovative approach to enhance Leishmaniasis therapy, aligning with the One Health concept by considering these treatments' environmental, veterinary, and public health impacts. By leveraging the adjustable properties of these nanomaterialsâincluding size, shape, and surface charge, tailored treatments for various diseases can be developed that are less harmful to the environment and nontarget species. We review recent advances in metal-, oxide-, and carbon-based nanomaterials for combating Leishmaniasis, examining their mechanisms of action and their dual use as standalone treatments or drug delivery systems. Our analysis highlights a promising yet underexplored frontier in employing these materials for more holistic and effective disease management.
Assuntos
Antiprotozoários , Leishmania , Leishmaniose , Nanoestruturas , Leishmaniose/tratamento farmacológico , Leishmaniose/parasitologia , Nanoestruturas/uso terapêutico , Humanos , Leishmania/efeitos dos fármacos , Antiprotozoários/uso terapêutico , Antiprotozoários/farmacologia , Animais , Sistemas de Liberação de MedicamentosRESUMO
BACKGROUND: Sepsis is a complex condition characterized by systemic host inflammation caused by an infection. Experimental and observational studies indicate that obesity, one of the components of metabolic syndrome (MetS), or aspirin (ASA) treatment could be associated with sepsis survival. However, the effects of ASA on septic mice with MetS-induced conditions have not been explored. METHODS: Swiss mice were administered monosodium glutamate (MSG) (4 mg/kg) during their first 5 days of life for MetS induction, while the control mice received an equimolar saline solution. MetS was validated in male mice on their 60th day of life. ASA treatment was administered for 15 days prior to sepsis (40 mg/kg). On the 75th day, sepsis was induced in MetS and control mice through cecal ligation and puncture (CLP). The effects of ASA on septic mice with MSG-induced MetS were assessed by determining survival rates, quantification of nitric oxide (NO), and cytokine levels in the plasma, while correlating these data with hematological, blood glucose and cardiovascular parameters. RESULTS: MetS was validated by Lee-Index (3 body weight/naso-anal length×1000), hypertension, and hyperglycemia in animals receiving MSG as neonates. In control animals, severe sepsis promoted hypoglycemia, which was associated with mortality, as well as increased plasma NO levels, hypotension, hematological alterations, and elevation of proinflammatory cytokines. In contrast, MetS and pre-treatment with ASA were able to prevent sepsis-related alterations. CONCLUSIONS: MetS and ASA pre-treatment provided protection against severe sepsis. However, ASA was ineffective in mice with MetS undergoing severe sepsis.
Assuntos
Aspirina , Citocinas , Síndrome Metabólica , Óxido Nítrico , Sepse , Animais , Sepse/tratamento farmacológico , Aspirina/uso terapêutico , Aspirina/administração & dosagem , Camundongos , Masculino , Síndrome Metabólica/tratamento farmacológico , Citocinas/sangue , Óxido Nítrico/metabolismo , Modelos Animais de Doenças , Glutamato de Sódio , Glicemia/análiseRESUMO
More sustainable materials have been becoming an important concern of worldwide scientists, and cellulosic materials are one alternative in water decontamination. An efficient strategy to improve removal capacity is functionalizing or incorporating nanomaterials in cellulose-based materials. The new hybrid cDAC/ZnONPs was produced by green synthesis of zinc oxide nanoparticles (ZnONPs), promoting the in situ reduction and immobilization on the cationic dialdehyde cellulose microfibers (cDAC) surface to remove Congo red dye from water. cDAC/ZnONPs was characterized by scanning electron microscopy (SEM-EDS) and infrared spectroscopy (FTIR), which showed efficient nanoparticles reduction. Adsorption efficiency on cationic cellulose surface was investigated by pH, contact time, initial concentration, and dye selectivity tests. The material followed the H isotherm model, which resulted in a maximum adsorption capacity of 1091.16 mg/g. Herein, was developed an efficient and ecologically correct new adsorbent, highly effective in Congo red dye adsorption even at high concentrations, suitable for the remediation of contaminated industrial effluents.