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1.
ARP Rheumatol ; 3(1): 49-52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558064

RESUMO

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder which may affect the gastrointestinal system. Half of the patients with SLE experience gastrointestinal symptoms, with the most common being nausea, vomiting, anorexia, and abdominal pain. Mesenteric vasculitis is a severe and rare complication of SLE and one of the most frequent causes of severe acute abdominal pain. The authors present a case of a 57-year-old woman with SLE who was diagnosed with necrotizing mesenteric vasculitis following a urinary septic shock. The patient was treated with high-dose corticosteroid therapy and cyclophosphamide, with resolution of the clinical picture.


Assuntos
Gastroenteropatias , Lúpus Eritematoso Sistêmico , Lesões do Sistema Vascular , Vasculite , Feminino , Humanos , Pessoa de Meia-Idade , Lúpus Eritematoso Sistêmico/complicações , Vasculite/complicações , Gastroenteropatias/complicações , Ciclofosfamida/uso terapêutico , Dor Abdominal/complicações , Lesões do Sistema Vascular/complicações
2.
Food Chem ; 449: 139184, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38579651

RESUMO

Fresh sea urchin (Paracentrotus lividus) gonads are a delicacy with short seasonal availability, very often heterogeneous in size and intrinsic characteristics. This study aimed to valorise this resource through the preparation of canned products (with/without Porphyra spp.) and evaluate their physicochemical and sensory quality (3-12 months). Canning contributed to a decrease in protein, K and most carotenoids contents; and a concentration of lipids, ash, Na and Se levels. A simulated 12-month ageing led to decrease the protein and ß-carotene contents; and the Na and lutein levels concentration. The macroalgae addition resulted in an orange, darker and less soft product, with higher carbohydrates, Na, Se and carotenoids contents. A 25 g-dose contributes to significant daily intakes of protein (8-9%), EPA+DHA (47-53%), I (35-62%) and Se (30-47%). The products were commercially stable/sterile and had good sensory acceptance. Overall, canning constitutes a strategy to provide a nutritionally balanced product available all year-round.

3.
J Hazard Mater ; 471: 134243, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38657506

RESUMO

Iron-magnetic nanoparticles (Fe-NMPs) are widely used in environmental remediation, while porphyrin-based hybrid materials anchored to silica-coated Fe3O4-nanoparticles (Fe3O4-NPs) have been used for water disinfection purposes. To assess their safety on plants, especially concerning potential environmental release, it was investigated for the first time, the impact on plants of a silica-coated Fe3O4-NPs bearing a porphyrinic formulation (FORM) - FORM@NMP. Additionally, FORM alone and the magnetic nanoparticles without FORM anchored (NH2@NMP) were used for comparison. Wheat (Triticum aestivum L.) was chosen as a model species and was subjected to three environmentally relevant doses during germination and tiller development through root application. Morphological, physiological, and metabolic parameters were assessed. Despite a modest biomass decrease and alterations in membrane properties, no major impairments in germination or seedling development were observed. During tiller phase, both Fe3O4-NPs increased leaf length, and photosynthesis exhibited varied impacts: both Fe3O4-NPs and FORM alone increased pigments; only Fe3O4-NPs promoted gas exchange; all treatments improved the photochemical phase. Regarding oxidative stress, lipid peroxidation decreased in FORM and FORM@NMP, yet with increased O2-• in FORM@NMP; total flavonoids decreased in NH2@NMP and antioxidant enzymes declined across all materials. Phenolic profiling revealed a generalized trend towards a decrease in flavones. In conclusion, these nanoparticles can modulate wheat physiology/metabolism without apparently inducing phytotoxicity at low doses and during short-time exposure. ENVIRONMENTAL IMPLICATION: Iron-magnetic nanoparticles are widely used in environmental remediation and fertilization, besides of new applications continuously being developed, making them emerging contaminants. Soil is a major sink for these nanoparticles and their fate and potential environmental risks in ecosystems must be addressed to achieve more sustainable environmental applications. Furthermore, as the reuse of treated wastewater for agricultural irrigation is being claimed, it is of major importance to disclose the impact on crops of the nanoparticles used for wastewater decontamination, such as those proposed in this work.

4.
Polymers (Basel) ; 16(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38611137

RESUMO

In this work, hybrid materials within the polydimethylsiloxane-silica (PDMS-SiO2) system, synthesized via the sol-gel method, were developed and characterized for their potential to incorporate and release the bioactive compound resveratrol (RES). RES was incorporated into the materials with a high loading efficiency (>75%) using the rotary evaporator technique. This incorporation induced the amorphization of RES, resulting in enhanced solubility and in vitro release when compared to the free polyphenolic compound. The release profiles displayed pH dependence, exhibiting notably faster release at pH 5.2 compared to pH 7.4. The gradual release of RES over time demonstrated an initial time lag of approximately 4 h, being well described by the Weibull model. In vitro cytotoxicity studies were conducted on human osteosarcoma cells (MG-63), revealing a concentration-dependent decrease in cell viability for RES-loaded samples (for concentrations >50 µg mL-1).

5.
Ecotoxicol Environ Saf ; 275: 116254, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38547729

RESUMO

Heavy metal exposure leads to multiple system dysfunctions. The mechanisms are likely multifactorial and involve inflammation and oxidative stress. The aim of this study was to evaluate markers and risk factors for atherosclerosis in the LDL receptor knockout mouse model chronically exposed to inorganic mercury (Hg) in the drinking water. Results revealed that Hg exposed mice present increased plasma levels of cholesterol, without alterations in glucose. As a major source and target of oxidants, we evaluated mitochondrial function. We found that liver mitochondria from Hg treated mice show worse respiratory control, lower oxidative phosphorylation efficiency and increased H2O2 release. In addition, Hg induced mitochondrial membrane permeability transition. Erythrocytes from Hg treated mice showed a 50% reduction in their ability to take up oxygen, lower levels of reduced glutathione (GSH) and of antioxidant enzymes (SOD, catalase and GPx). The Hg treatment disturbed immune system cells counting and function. While lymphocytes were reduced, monocytes, eosinophils and neutrophils were increased. Peritoneal macrophages from Hg treated mice showed increased phagocytic activity. Hg exposed mice tissues present metal impregnation and parenchymal architecture alterations. In agreement, increased systemic markers of liver and kidney dysfunction were observed. Plasma, liver and kidney oxidative damage indicators (MDA and carbonyl) were increased while GSH and thiol groups were diminished by Hg exposure. Importantly, atherosclerotic lesion size in the aorta root of Hg exposed mice were larger than in controls. In conclusion, in vivo chronic exposure to Hg worsens the hypercholesterolemia, impairs mitochondrial bioenergetics and redox function, alters immune cells profile and function, causes several tissues oxidative damage and accelerates atherosclerosis development.


Assuntos
Aterosclerose , Hipercolesterolemia , Mercúrio , Animais , Camundongos , Aterosclerose/induzido quimicamente , Peróxido de Hidrogênio , Nefropatias , Mercúrio/toxicidade , Camundongos Knockout , Estresse Oxidativo/fisiologia , Receptores de LDL/genética
6.
Vet Clin Pathol ; 53(1): 85-92, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38418390

RESUMO

Telangiectatic osteosarcoma is a rare variant of osteosarcoma histologically and clinically similar to hemangiosarcoma (HSA). This case series describes the imaging and cytologic features of four histologically confirmed telangiectatic osteosarcomas, including the use of cytochemical stains. Alkaline phosphatase (ALP) was applied to Wright-Giemsa-stained cytology slides, and Factor VIII immunohistochemistry was evaluated. Cytologic characteristics included atypical mesenchymal cells with evidence of acute and chronic hemorrhage. Telangiectatic osteosarcoma cases had positive ALP cytochemical staining, while control HSA cases were negative. Factor VIII immunohistochemistry was negative in telangiectatic osteosarcoma and positive in HSA. Cytologic diagnosis of telangiectatic osteosarcoma with positive ALP cytochemical staining can help differentiate this neoplasm from HSA.


Assuntos
Neoplasias Ósseas , Doenças do Cão , Hemangiossarcoma , Osteossarcoma , Cães , Animais , Fator VIII , Doenças do Cão/diagnóstico , Osteossarcoma/diagnóstico , Osteossarcoma/veterinária , Hemangiossarcoma/patologia , Hemangiossarcoma/veterinária , Corantes , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/veterinária
7.
Toxicon ; 240: 107653, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38387755

RESUMO

Population growth leads to the need for more efficient techniques and compounds in agriculture, such as pesticides, to deal with the ever-growing demand. Pesticides may end up in the environment, often compromising the ecosystem affecting all organisms including humans. Therefore, the consequences of exposure to these compounds to biota and humans needs to be assessed. Bearing this in mind, the aim of this study was to examine the in vitro cytotoxicity and genotoxicity attributed to exposure to the biopesticide Turex® utilizing the liver cell line HepG2. Cells were incubated with biopesticide Turex® at 250, 500, 1000, 1500 or 2000 µg/L in both non-activated and activated forms for 24 and 48 h. Subsequent effects on cell viability were assessed using the MTT. The influence on cell cycle dynamics was determined by flow cytometry, while DNA damage was measured by the comet assay. Data demonstrated that activated Turex® induced cytotoxicity and DNA damage after 48 h in HepG2 cell line. The cell cycle progression was not markedly affected by Turex® at any concentration or duration of exposure. In conclusion, data demonstrated the potential adverse effects attributed to exposure to biopesticide Turex® in human cell line HepG2. Consequently, this type of biopesticide needs to be further investigated to determine the potential adverse in vivo effects on various non-target organisms.


Assuntos
Agentes de Controle Biológico , Praguicidas , Humanos , Células Hep G2 , Agentes de Controle Biológico/farmacologia , Ecossistema , Dano ao DNA , Pontos de Checagem do Ciclo Celular , Praguicidas/toxicidade , Ciclo Celular , Sobrevivência Celular
8.
Biochimie ; 216: 99-107, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37879427

RESUMO

Cancer is a huge public health problem being one of the main causes of death globally. Specifically, melanoma is one of the most threatening cancer types due to the metastatic capacity, treatment resistance and mortality rates. It is evident the urgent need for research on new agents with pharmacological potential for cancer treatment, in order to develop new cancer therapeutic strategies and overcome drug resistance. The present work investigated the anti-tumoral potential of Chartergellus-CP1 peptide, isolated from Chartergellus communis wasp venom on human melanoma cell lines with different pigmentation degrees, namely the amelanotic cell line A375 and pigmented cell line MNT-1. Chartergellus-CP1 induced selective cytotoxicity to melanoma cell lines when compared to the lower induced cytotoxicity towards to nontumorigenic keratinocytes. Chartergellus-CP1 peptide induced apoptosis in both melanoma cell lines, cell cycle impairment in amelanotic A375 cells and intracellular ROS increase in pigmented MNT-1 cells. The amelanotic A375 cell line showed higher sensitivity to the peptide than the pigmented cell line MNT-1. From our knowledge, this is the first study reporting the cytotoxic effects of Chartergellus-CP1 on melanoma cells.


Assuntos
Antineoplásicos , Melanoma , Humanos , Melanoma/patologia , Venenos de Vespas/farmacologia , Venenos de Vespas/uso terapêutico , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Apoptose
9.
Dent Mater ; 40(1): 80-89, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37919111

RESUMO

OBJECTIVES: To evaluate the effect of mono and multi-wave light-curing units (LCUs) on the Knoop hardness of resin-based composites (RBC) that use different photoinitiators. METHODS: Central incisor-shaped specimens 12 mm long, 9 mm wide, and 1.5 mm thick were made from 2 RBCs that use different photoinitiators: Tetric N-Ceram (Ivoclar Vivadent) - and Vittra APS (FGM), both A2E shade. They were light-cured with 4 different LCUs: two claimed to be multi-wave - VALO Grand (Ultradent) and Emitter Now Duo (Schuster); and two were monowave - Radii Xpert (SDI) and Elipar DeepCure-L (3 M Oral Care) using 2 different light exposure protocols: one 40 s exposure centered over the specimen; and two 20 s light exposures that delivered light from two positions to better cover the entire tooth. 16 groups with 10 specimens in each group were made. The Knoop hardness (KH, kg/mm2) was measured at the top and bottom of the specimen in the center and at the cervical, incisal, mesial, and distal peripheral regions. The active tip diameters (mm) and spectral radiant powers (mW/nm) of the LCUs were measured with and without the interposition of the RBC, as well as the radiant exposure beam profiles (J/cm²) delivered to the top of the RBCs. The data was analyzed using Three-way ANOVA and Tukey's tests (α = 0.05). RESULTS: The VALO Grand (1029 mW) emitted twice the power of the Radii Xpert (500 mW). The KH values of VI and TN resin composite specimens were significantly affected by the LCU used (p < .001), the measurement location (p < .001), and the surface of the specimen (p < .001). LCUs with wider tip diameters produced greater Knoop hardness values at the peripheries of the 12 mm of long, 9 mm wide specimens. In general, the VALO Grand produced the highest KH values, followed by Elipar DeepCure-L, then by Radii Xpert. The Emitter Now Duo LCU produced the lowest values. Exposing the veneers from two locations reduced the differences between the LCUs and the effect of the measurement location. Only the VALO Grand could fully cover the composite veneer with light when the two locations were used. SIGNIFICANCE: The light tip must cover the entire restoration to photocure the RBC beneath the light tip.


Assuntos
Luzes de Cura Dentária , Cura Luminosa de Adesivos Dentários , Dureza , Teste de Materiais , Resinas Compostas , Materiais Dentários , Polimerização
10.
Adv Healthc Mater ; : e2303861, 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38041539

RESUMO

Responsive magnetic nanomaterials offer significant advantages for innovative therapies, for instance, in cancer treatments that exploit on-demand delivery on alternating magnetic field (AMF) stimulus. In this work, biocompatible magnetic bionanocomposite films are fabricated from chitosan by film casting with incorporation of magnetite nanoparticles (MNPs) produced by facile one pot synthesis. The influence of synthesis conditions and MNP concentration on the films' heating efficiency and heat dissipation are evaluated through spatio-temporal mapping of the surface temperature changes by video-thermography. The cast films have a thickness below 100 µm, and upon exposure to AMF (663 kHz, 12.8 kA m-1 ), induce exceptionally strong heating, reaching a maximum temperature increase of 82 °C within 270 s irradiation. Further, it is demonstrated that the films can serve as substrates that supply heat for multiple hyperthermia scenarios, including: i) non-contact automated heating of cell culture medium, ii) heating of gelatine-based hydrogels of different shapes, and iii) killing of cancerous melanoma cells. The films are versatile components for non-contact stimulus with translational potential in multiple biomedical applications.

11.
Int J Mol Sci ; 24(23)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38069233

RESUMO

Atmospheric particulate matter (PM) with diameters below 10 µm (PM10) may enter the lungs through inhalation and are linked to various negative health consequences. Emergent evidence emphasizes the significance of cell metabolism as a sensitive target of PM exposure. However, the current understanding of the relationship between PM composition, conventional toxicity measures, and the rewiring of intracellular metabolic processes remains limited. In this work, PM10 sampled at a residential area (urban background, UB) and a traffic-impacted location (roadside, RS) of a Portuguese city was comprehensively characterized in terms of polycyclic aromatic hydrocarbons and plasticizers. Epithelial lung cells (A549) were then exposed for 72 h to PM10 organic extracts and different biological outcomes were assessed. UB and RS PM10 extracts dose-dependently decreased cell viability, induced reactive oxygen species (ROS), decreased mitochondrial membrane potential, caused cell cycle arrest at the G0/G1 phase, and modulated the intracellular metabolic profile. Interestingly, the RS sample, richer in particularly toxic PAHs and plasticizers, had a greater metabolic impact than the UB extract. Changes comprised significant increases in glutathione, reflecting activation of antioxidant defences to counterbalance ROS production, together with increases in lactate, NAD+, and ATP, which suggest stimulation of glycolytic energy production, possibly to compensate for reduced mitochondrial activity. Furthermore, a number of other metabolic variations hinted at changes in membrane turnover and TCA cycle dynamics, which represent novel clues on potential PM10 biological effects.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Material Particulado/toxicidade , Material Particulado/análise , Poluentes Atmosféricos/análise , Espécies Reativas de Oxigênio/farmacologia , Plastificantes/farmacologia , Pulmão/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Monitoramento Ambiental
12.
J Appl Oral Sci ; 31: e20230241, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37909530

RESUMO

OBJECTIVE: The use of a fiber glass post (FGP) type and choice of FGP diameter to restore endodontically treated incisors without ferrule is controversial. This study evaluated survival rate and failure mode of severely compromised central incisors without ferrule rehabilitated using resin-based composite (RBC) with or without FGP with different diameters. METHODOLOGY: A total of 60 decoronated bovine incisors without a ferrule were endodontically treated and prepared for 1.4, 1.6, and 1.8 mm diameter FGPs (Whitepost System DC 0.5, Fit 0.4, and DCE 0.5; FGM). Half of the teeth received FGPs cemented using dual-cure resin cement (Allcem Core; FGM), the other half were filled using only bulk-fill RBC (OPUS Bulk Fill; FGM). The crowns were directly restored with RBC. The roots were embedded in polystyrene resin and the periodontal ligament was simulated with polyether impression material. Fatigue testing was conducted under 5 Hz cyclic loading at 30 degrees to the incisal edge, beginning at 50 N (5,000 cycles) as a warmup. After, the load was increased 100 N every 15,000 cycles until fracture occurred. All specimens were subjected to transillumination, micro-CT analysis, and digital radiography before and after fatigue testing. Fracture mode was classified according to severity and repair potential. Data were analyzed with Kaplan-Meier survival test and post hoc log-rank test (α=0.05) for pairwise comparisons. RESULTS: Using FGP significantly increased the number of cycles to failure, irrespective of FGP diameters (p=0.001). The FGP diameters had no statistically significant effect on cycles to failure or failure mode. CONCLUSION: Using FGP without ferrule improved survival rate of structurally severely compromised central incisors compared with rehabilitation without FGP. The diameter of the FGPs had no effect on the survival rate and failure mode.


Assuntos
Técnica para Retentor Intrarradicular , Fraturas dos Dentes , Dente não Vital , Animais , Bovinos , Resinas Compostas , Coroas , Materiais Dentários , Vidro , Análise do Estresse Dentário , Falha de Restauração Dentária
13.
Biomolecules ; 13(10)2023 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-37892238

RESUMO

CETP activity reduces plasma HDL-cholesterol concentrations, a correlate of an increased risk of atherosclerotic events. However, our recent findings suggest that CETP expression in macrophages promotes an intracellular antioxidant state, reduces free cholesterol accumulation and phagocytosis, and attenuates pro-inflammatory gene expression. To determine whether CETP expression in macrophages affects atherosclerosis development, we transplanted bone marrow from transgenic mice expressing simian CETP or non-expressing littermates into hypercholesterolemic LDL-receptor-deficient mice. The CETP expression did not change the lipid-stained lesion areas but decreased the macrophage content (CD68), neutrophil accumulation (LY6G), and TNF-α aorta content of young male transplanted mice and decreased LY6G, TNF-α, iNOS, and nitrotyrosine (3-NT) in aged female transplanted mice. These findings suggest that CETP expression in bone-marrow-derived cells reduces the inflammatory features of atherosclerosis. These novel mechanistic observations may help to explain the failure of CETP inhibitors in reducing atherosclerotic events in humans.


Assuntos
Aterosclerose , Medula Óssea , Humanos , Camundongos , Animais , Masculino , Feminino , Idoso , Medula Óssea/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas de Transferência de Ésteres de Colesterol/genética , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Aterosclerose/metabolismo , Colesterol/metabolismo , Camundongos Transgênicos , Camundongos Endogâmicos C57BL
14.
Cell Physiol Biochem ; 57(5): 331-344, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37724045

RESUMO

BACKGROUND/AIMS: Recombinant adeno-associated viruses (rAAV) are an important tool for lung targeted gene therapy. Substitution of tyrosine with phenylalanine residues (Y-F) in the capsid have been shown to protect the AAV vector from ubiquitin/proteasome degradation, increasing transduction efficiency. We tested the mutant Y733F-AAV8 vector for mucus diffusion, as well as the safety and efficacy of pigment epithelium-derived factor (PEDF) gene transfer to the lung. METHODS: For this purpose, Y733F-AAV8-PEDF (1010 viral genome) was administered intratracheally to C57BL/6 mice. Lung mechanics, morphometry, and inflammation were evaluated 7, 14, 21, and 28 days after injection. RESULTS: The tyrosine-mutant AAV8 vector was efficient at penetrating mucus in ex vivo assays and at transferring the gene to lung cells after in vivo instillation. Increased levels of transgene mRNA were observed 28 days after vector administration. Overexpression of PEDF did not affect in vivo lung parameters. CONCLUSION: These findings provide a basis for further development of Y733F-AAV8-based gene therapies for safe and effective delivery of PEDF, which has anti-angiogenic, anti-inflammatory and anti-fibrotic activities and might be a promising therapy for lung inflammatory disorders.


Assuntos
Proteínas do Olho , Técnicas de Transferência de Genes , Serpinas , Animais , Camundongos , Proteínas do Olho/genética , Camundongos Endogâmicos C57BL , Fatores de Crescimento Neural/genética , Serpinas/genética
15.
ACS Appl Mater Interfaces ; 15(34): 40898-40912, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37584276

RESUMO

3D bioprinting is a versatile technique that allows the fabrication of living tissue analogs through the layer-by-layer deposition of cell-laden biomaterials, viz. bioinks. In this work, composite alginate hydrogel-based bioinks reinforced with curcumin-loaded particles of cellulose esters (CEpCUR) and laden with human keratinocytes (HaCaT) are developed. The addition of the CEpCUR particles, with sizes of 740 ± 147 nm, improves the rheological properties of the inks, increasing their shear stress and viscosity, while preserving the recovery rate and the mechanical and viscoelastic properties of the resulting fully cross-linked hydrogels. Moreover, the presence of these particles reduces the degradation rate of the hydrogels from 26.3 ± 0.8% (ALG) to 18.7 ± 1.3% (ALG:CEpCUR_10%) after 3 days in the culture medium. The 3D structures printed with the ALG:CEpCUR inks reveal increased printing definition and the ability to release curcumin (with nearly 70% of cumulative release after 24 h in PBS). After being laden with HaCaT cells (1.2 × 106 cells mL-1), the ALG:CEpCUR bioinks can be successfully 3D bioprinted, and the obtained living constructs show good dimensional stability and high cell viabilities at 7 days post-bioprinting (nearly 90%), confirming their great potential for application in fields like wound healing.


Assuntos
Bioimpressão , Curcumina , Humanos , Hidrogéis/química , Curcumina/farmacologia , Celulose , Alginatos/química , Impressão Tridimensional , Tecidos Suporte/química , Bioimpressão/métodos , Engenharia Tecidual/métodos
16.
Mater Today Bio ; 22: 100733, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37533730

RESUMO

Antimicrobial photodynamic therapy (aPDT) is a potent tool to surpass the global rise of antimicrobial resistance; still, the effective topical administration of photosensitizers remains a challenge. Biopolymer-based adhesive films can safely extend the residence time of photosensitizers. However, their wide application is narrowed by their limited water absorption capacity and gel strength. In this study, pullulan-based films with a switchable character (from a solid film to an adhesive hydrogel) were developed. This was accomplished by the incorporation of a betaine-based deep eutectic solvent (DES) containing curcumin (4.4 µg.cm-2) into the pullulan films, which tuned the films' skin moisture absorption ability, and therefore they switch into an adhesive hydrogel capable of delivering the photosensitizer. The obtained transparent films presented higher extensibility (elongation at break up to 338.2%) than the pullulan counterparts (6.08%), when stored at 54% of relative humidity, and the corresponding hydrogels a 4-fold higher adhesiveness than commercial hydrogels. These non-cytotoxic adhesives allowed the inactivation (∼5 log reduction), down to the detection limit of the method, of multiresistant strains of Staphylococcus aureus in ex vivo skin samples. Overall, these materials are promising for aPDT in the treatment of resistant skin infections, while being easily removed from the skin.

17.
Am J Physiol Heart Circ Physiol ; 325(3): H592-H600, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37539470

RESUMO

Endothelial dysfunction is an early manifestation of atherosclerosis. The cholesteryl ester transfer protein (CETP) has been considered proatherogenic by reducing plasma HDL levels. However, CETP may exhibit cell- or tissue-specific effects. We have previously reported that male mice expressing the human CETP gene show impaired endothelium-mediated vascular relaxation associated with oxidative stress. Although sexual dimorphisms on the metabolic role of CETP have been proposed, possible sex differences in the vascular effects of CETP were not previously studied. Thus, here we investigated the endothelial function of female CETP transgenic mice as compared with nontransgenic controls (NTg). Aortas from CETP females presented preserved endothelium-dependent relaxation to acetylcholine and an endothelium-dependent reduction of phenylephrine-induced contraction. eNOS phosphorylation (Ser1177) and calcium-induced NO levels were enhanced, whereas reactive oxygen species (ROS) production and NOX2 and SOD2 expression were reduced in the CETP female aortas. Furthermore, CETP females exhibited increased aortic relaxation to 17ß-estradiol (E2) and upregulation of heat shock protein 90 (HSP90) and caveolin-1, proteins that stabilize estrogen receptor (ER) in the caveolae. Indeed, CETP females showed an increased E2-induced relaxation in a manner sensitive to estrogen receptor-α (ERα) and HSP90 inhibitors methylpiperidinopyrazole (MPP) and geldanamycin, respectively. MPP also impaired the relaxation response to acetylcholine in CETP but not in NTg females. Altogether, the study indicates that CETP expression ameliorates the anticontractile endothelial effect and relaxation to E2 in females. This was associated with less ROS production, and increased eNOS-NO and E2-ERα pathways. These results highlight the need for considering the sex-specific effects of CETP on cardiovascular risk.NEW & NOTEWORTHY Here we demonstrated that CETP expression has a sex-specific impact on the endothelium function. Contrary to what was described for males, CETP-expressing females present preserved endothelium-dependent relaxation to acetylcholine and improved relaxation response to 17ß-estradiol. This was associated with less ROS production, increased eNOS-derived NO, and increased expression of proteins that stabilize estrogen receptor-α (ERα), thus increasing E2-ERα signaling sensitivity. These results highlight the need for considering the sex-specific effects of CETP on cardiovascular risk.


Assuntos
Proteínas de Transferência de Ésteres de Colesterol , Receptor alfa de Estrogênio , Óxido Nítrico Sintase Tipo III , Animais , Feminino , Camundongos , Acetilcolina/farmacologia , Proteínas de Transferência de Ésteres de Colesterol/genética , Endotélio/metabolismo , Endotélio Vascular/metabolismo , Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Vasodilatação
18.
Environ Sci Pollut Res Int ; 30(37): 87242-87259, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37421522

RESUMO

This study aimed to comprehensively assess the performance of HKUST-1, a metal-organic framework (MOF), as an adsorbent for various classes of textile dyes, including direct, acid, basic, and vinyl sulfonic reactive dyes. Real-world dyeing scenarios were simulated using carefully selected combinations of dyes to evaluate HKUST-1's effectiveness in treating dyeing process effluents. The results demonstrated that HKUST-1 exhibited highly efficient adsorption capabilities across all dye classes. Isolated direct dyes showed the best adsorption outcomes, with adsorption percentages exceeding 75% and reaching 100% for direct blue dye (Sirius Blue K-CFN). Basic dyes exhibited adsorption levels of nearly 85% for blue dye (Astrazon Blue FG), while the adsorption performance for the yellow dye (Yellow GL-E) was the poorest. The adsorption of dyes in combined systems followed a similar trend to that of isolated dyes, with the trichromy of direct dyes yielding the best results. Kinetic studies indicated that the adsorption of dyes followed a pseudo-second-order model, with nearly instantaneous adsorption observed in all cases. Furthermore, most dyes adhered to the Langmuir isotherm, further confirming the effectiveness of the adsorption process. The exothermic nature of the adsorption process was evident. Importantly, the study demonstrated the feasibility of reusing the HKUST-1, highlighting its potential as an exceptional adsorbent for removing hazardous textile dyes from effluents.


Assuntos
Estruturas Metalorgânicas , Poluentes Químicos da Água , Cinética , Corantes , Adsorção , Têxteis
19.
Molecules ; 28(12)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37375331

RESUMO

Melanoma incidence, a type of skin cancer, has been increasing worldwide. There is a strong need to develop new therapeutic strategies to improve melanoma treatment. Morin is a bioflavonoid with the potential for use in the treatment of cancer, including melanoma. However, therapeutic applications of morin are restrained owing to its low aqueous solubility and limited bioavailability. This work investigates morin hydrate (MH) encapsulation in mesoporous silica nanoparticles (MSNs) to enhance morin bioavailability and consequently increase the antitumor effects in melanoma cells. Spheroidal MSNs with a mean size of 56.3 ± 6.5 nm and a specific surface area of 816 m2/g were synthesized. MH was successfully loaded (MH-MSN) using the evaporation method, with a loading capacity of 28.3% and loading efficiency of 99.1%. In vitro release studies showed that morin release from MH-MSNs was enhanced at pH 5.2, indicating increased flavonoid solubility. The in vitro cytotoxicity of MH and MH-MSNs on human A375, MNT-1 and SK-MEL-28 melanoma cell lines was investigated. Exposure to MSNs did not affect the cell viability of any of the cell lines tested, suggesting that the nanoparticles are biocompatible. The effect of MH and MH-MSNs on reducing cell viability was time- and concentration-dependent in all melanoma cell lines. The A375 and SK-MEL-28 cell lines were slightly more sensitive than MNT-1 cells in both the MH and MH-MSN treatments. Our findings suggest that MH-MSNs are a promising delivery system for the treatment of melanoma.


Assuntos
Melanoma , Nanopartículas , Humanos , Dióxido de Silício , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos , Melanoma/tratamento farmacológico , Flavonoides/farmacologia , Porosidade
20.
Pharmaceuticals (Basel) ; 16(6)2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37375852

RESUMO

Lycopene is a carotenoid with potential use in the treatment of chronic illnesses. Here, different formulations of lycopene were studied: lycopene-rich extract from red guava (LEG), purified lycopene from red guava (LPG) and a self-emulsifying drug delivery system loaded with LPG (nanoLPG). The effects of administering orally various doses of LEG to hypercholesterolemic hamsters were evaluated regarding the liver function of the animals. The cytotoxicity of LPG in Vero cells was analyzed by a crystal violet assay and by fluorescence microscopy. In addition, nanoLPG was employed in stability tests. LPG and nanoLPG were tested for their cytotoxic effect on human keratinocytes and antioxidant capacity on cells in an endothelial dysfunction model in an isolated rat aorta. Finally, the effect of different nanoLPG concentrations on the expression of immune-related genes (IL-10, TNF-α, COX-2 and IFN-γ) from peripheral blood mononuclear cells (PBMC) using real-time PCR was also analyzed. Results suggest that LEG, despite not being able to improve blood markers indicative of liver function in hypercholesterolemic hamsters, reduced hepatic degenerative changes. Additionally, LPG did not show cytotoxicity in Vero cells. In relation to nanoLPG, the effects produced by heat stress evaluated by Dynamics Light Scattering (DLS) and visually were loss of color, texture change and phase separation after 15 days without interfering with the droplet size, so the formulation proved to be efficient in stabilizing the encapsulated lycopene. Although LPG and nanoLPG showed moderate toxicity to keratinocytes, which may be related to cell lineage characteristics, both revealed potent antioxidant activity. LPG and nanoLPG showed vasoprotective effects in aortic preparations. The gene expression assay indicates that, although no significant differences were observed in the expression of IL-10 and TNF-α, the PBMCs treated with nanoLPG showed a reduction in transcriptional levels of IFN-γ and an increased expression of COX-2. Thus, the work adds evidence to the safety of the use of lycopene by humans and shows that tested formulations, mainly nanoLPG due to its stability, stand out as promising and biosafe products for the treatment of diseases that have oxidative stress and inflammation in their etiopathology.

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