RESUMO
In this study, polycaprolactone/gelatin (PCL/GEL) electrospun nanofibers containing biogenic selenium nanoparticles (Se NPs) and Se NPs/vitamin E (VE) with average diameters of 397.8 nm and 279.5 nm, respectively (as determined by SEM inspection) were prepared and their effect on wound healing was evaluated using in-vivo studies. The energy dispersive X-ray (EDX) mapping, TEM micrograph, and FTIR spectra of the prepared nanofibers strongly demonstrated well entrapment of Se NPs and VE into scaffolds. An amount of 57% Se NPs and 43% VE were gradually released from PCL/GEL/Se NPs/VE scaffold after 4 days immersion in PBS solution (pH 7.4). The both PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds supported 3T3 cell proliferation and attachment as confirmed by MTT assay and SEM imaging. Complete re-epithelialization, low level of edema and inflammatory cells in coordination with high level of oriented collagens demonstrated the wound healing activity of PCL/GEL/Se NPs/VE. Besides, significant antioxidant efficacy of PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds was demonstrated according to GSH and MDA assays. To sum up, the prepared PCL/GEL/Se NPs/VE scaffold in the present study represented suitable healing effect on animal model which candidate it for further studies.
Assuntos
Bandagens , Gelatina/química , Nanofibras/química , Nanopartículas/química , Poliésteres/química , Vitamina E/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Masculino , Camundongos , Nanofibras/toxicidade , Ratos , Ratos Wistar , Reepitelização/efeitos dos fármacos , Selênio/química , Pele/patologia , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacosRESUMO
The goal of this survey is to evaluate the anti-proliferative effects of the hydroalcholic extract of Blepharis persica seeds and its synergic effect on doxorubicin (DOX) in human colon cancer (HT-29) and gastric cancer cell (AGS) lines. 70% Ethanol was used for extraction of B. persica seed. Aluminum-chloride colorimetric and Folin-Ciocalteu reagent methods were used to measure total flavonoid and total phenolic contents of the extract respectively. Gas chromatography-mass spectrometry (GC-MS) analysis of the B. persica extract was performed on GC-MS equipment after silylation. HT-29, AGS, and human fibroblast (SKM) cell lines were treated by different concentration of the B. persica extract, (DOX) and the combination of extraction and DOX. The cytotoxicity was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay while the apoptosis induction was monitored using flowcytometry by annexin-V FITC/PI double-staining. The changes in expression levels of BAX and BCL-2 were determined using Real-Time RT-qPCR. GC-MS analysis of the hydroalcoholic extract from B. persica seeds revealed 24 major components. The MTT assay revealed the cytotoxicity against three cell lines and also it was shown that 125 ng/mL of DOX and 0.625 mg/mL of B. persica extract had synergistic behavior against HT29 cell line. These results showed B. persica extract induced apoptosis in AGS and HT29 cells and its extract caused dose-dependent increase in up-regulation of BAX level (p < 0.05) and down-regulation of BCL2 (p < 0.05). B. persica showed the synergistic effect in combination with DOX on HT29 cell line. These findings demonstrated a basis for further studies on the characterization and mechanistic evaluation of the bioactive compounds of B. persica extract which had antiproliferative effects on cancer cell lines.
Assuntos
Acanthaceae/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Células HT29/efeitos dos fármacos , Humanos , Sementes/metabolismo , Neoplasias Gástricas/metabolismoRESUMO
Nickel-ferrite (NiFe2O4) nanorods particles (NRP) was biosynthesised for the first time by the Rosemary Extract. The NRP was fully characterised, including the type, nanostructure and physicochemical properties of using XRD, HRTEM, FeSEM, XPS, FTIR and VSM. TEM confirmed rod-shaped nano-sized particles with average sizes ranging from 10 nm to 28 nm. The EDAX Analysis showed the presence of iron, nickel, oxygen, and carbon. XRD analysis confirmed the synthesis of NiFe2O4 crystals. XPS curves showed photoelectron for iron, oxygen and nickel. EDS showed the atomic, weight percentages ratios of Ni(12%): Fe(24%) and: O(48) are close to the theoretical value (Ni: Fe:O = 1:2:4), of bimetallic magnetic NiFe2O4 NRP. NiFe2O4 NRP had cytotoxicity effect on MCF-7 cells survival which suggests that NiFe2O4 NRP can be used as a new class of anticancer agent in design novel cancer therapy research.
Assuntos
Compostos Férricos/química , Nanopartículas/química , Nanotecnologia , Nanotubos/química , Níquel/química , Rosmarinus/química , Técnicas de Química Sintética , Química Verde , Extratos Vegetais/metabolismoRESUMO
Thymoquinone (TQ), a phytochemical compound found in Carum carvil seeds (C. carvil), has a lot of applications in medical especially cancer therapy. However, TQ has a hydrophobic nature, and because of that, its solubility, permeability and its bioavailability in biological mediums are poor. To diminish these drawbacks, we have designed a herbal carrier composed of Ergosterol (herbal lipid), Carum carvil extract (Carum) and nonionic surfactants for herbal cancer treatment. C. carvil was extracted and characterized by GC/Mass. Two different formulations containing TQ and Carum were encapsulated into niosomes (Nio/TQ and Nio/Carum, respectively) and their properties were compared together. Morphology, size, zeta potential, encapsulation efficiency (EE%), profile release rate, in vitro cytotoxicity, flow cytometric, DNA fragmentation and cell migration assay of formulations were evaluated. Results show that both loaded formulations have a spherical morphology, nanometric size and negative zeta potential. EE% of TQ and Carum loaded niosomes was about 92.32% ± 2.32 and 86.25% ± 1.85, respectively. Both loaded formulations provided a controlled release compared with free TQ. MTT assay showed that loaded niosomes have more anti-cancer activity compared with Free TQ and free Carum against MCF-7 cancer cell line and these results were confirmed by flow cytometric analysis. Cell cycle analysis showed G2/M arrest in TQ, Nio/TQ and Nio/Carum formulations. TQ, Nio/TQ and Nio/Carum decreased the migration of MCF7 cells remarkedly. These results show that the TQ and Carum loaded niosomes are novel carriers with high efficiency for encapsulation of low soluble phytochemicals and also would be favourable systems for breast cancer treatment.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/genética , Carum/química , Antineoplásicos Fitogênicos/química , Benzoquinonas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA , Preparações de Ação Retardada , Feminino , Humanos , Lipossomos/química , Células MCF-7 , Extratos Vegetais/químicaRESUMO
Phytochemicals like Lawsone have some drawbacks that stem from their poor solubility. Low solubility in aqueous mediums results in low bioavailability, poor permeability and instability of phytochemical compounds in biological environments. The aim of this study was to design nanoniosomes containing Lawsone (Law) using non-ionic surfactants and cholesterol. Niosomes were prepared by thin film hydration method (TFH). Then, they were loaded with Henna extract (HLaw) and standard Lawsone (SLaw), and two resulted formulations were compared. The henna extract was analyzed by mass gas chromatography. Size, zeta potential, polydispersity index (PDI) and morphology of the loaded formulations were evaluated by dynamic light scattering (DLS) and scanning electron spectroscopy (SEM). The incorporation and release rate of Law from niosome bilayers were evaluated by UV-Vis spectroscopy. In vitro experiments were carried out to evaluate antitumor activity in MCF-7 cell line. The results showed distinct spherical shapes and particle sizes were about 250 nm in diameter and have negative zeta potentials. Niosomes were stable at 4 °C for 2 months. Entrapment efficiently of both formulations was about 70% and showed a sustained release profile. In vitro study exhibited that using of niosome to encapsulating Law can significantly increase antitumor activity of formulation in MCF-7 cell line compared to Law solution (free Law). Thus, niosomes are a promising carrier system for delivery of phytochemical compounds that have poor solubility in biological fluids. Graphical abstract á .
Assuntos
Naftoquinonas/administração & dosagem , Naftoquinonas/farmacologia , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colesterol/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Lawsonia (Planta)/química , Lipossomos , Tamanho da Partícula , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Propriedades de Superfície , Tensoativos/químicaRESUMO
The synthesis and characterization of three dioxo U(VI) complexes, [UO2(L1)(OH2)], [UO2(L2)DMF], and [UO2(L2)DMSO], [L1]2- = 1,1'-(4-methyl-1,2-phenylenebis (nitrilomethylidyne))di-2-naphtholate: [L2]2- = 1,1'-(o-phenylenebis (nitrilomethylidyne)) di-2-naphtholate, are reported. Elemental analysis, FT-IR, 1HNMR, UV-Vis spectroscopy, molar conductivity and single crystal X-ray diffraction were used to characterize the complexes. It was found that the complexes adopt a distorted pentagonal bipyramidal coordination geometry. The interaction of the synthesized complexes with DNA and bovine serum albumin was thoroughly investigated using both experimental and theoretical studies. UV-Vis absorption and fluorescence quenching techniques were applied to determine the binding parameters as well as the mechanism of the interaction of each complex with DNA and the protein. The results obtained suggested that interaction of the complexes with DNA occurred through partial intercalation into the minor grooves of DNA with binding constants in the range of 0.661 × 105-1.56 × 105 M-1. In addition, interaction of the complexes with bovine serum albumin quenched the fluorescence emission of the tryptophan residues of the protein binding constants and thermodynamic parameters were obtained from the fluorescence quenching experiments at different temperatures. The values of binding constants revealed moderate interactions between the synthesized complexes and the protein suggesting that this protein could act as a suitable vehicle for transportation of the compounds. The results of molecular docking confirmed those of the experimental studies. The anticancer properties of the title complexes were also evaluated through a study of the in vitro cytotoxicity of the compounds against the HT-29 and MCF-7 cancer cell lines and the DPSC normal cell line using an MTT assay.
Assuntos
Antineoplásicos/farmacologia , Compostos Organometálicos/farmacologia , Salicilatos/farmacologia , Urânio/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Sítios de Ligação/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , DNA de Neoplasias/química , DNA de Neoplasias/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Salicilatos/química , Soroalbumina Bovina/química , Soroalbumina Bovina/efeitos dos fármacos , Relação Estrutura-Atividade , Termodinâmica , Células Tumorais Cultivadas , Urânio/químicaRESUMO
A mononuclear dioxido-uranium(IV) complex [UO2(L)(DMSO)2], was prepared from the reaction of (2-hydroxy-3-methoxybenzylidene)benzohydrazide [HL] with UO2(OAc)2·2H2O in DMSO. The obtained complex was fully characterized. Single crystal X-ray diffraction analysis of [UO2(L)(DMSO)2] revealed that U(VI) ion has been coordinated by ONO donor atoms of the dianionic ligand (L(2-)), oxo groups and two DMSO molecules in a pentagonal bipyramid geometry. In addition, interactions of the complex with salmon sperm DNA and bovine serum albumin (BSA) were thoroughly investigated using UV-vis absorption, voltammetry and molecular docking methods. The experimental studies showed an intercalative mode of interaction between the complex and DNA. Experiments on BSA interaction indicated a change in the polarity of the environment surrounded the complex as a result of the interaction between BSA and [UO2(L)(DMSO)2]. Finally, MTT assays indicated that the U(VI) complex had excellent cytotoxicity against human carcinoma cell lines of MCF-7, HPG-2, and HT-29, with IC50 values of 8.4, 10.6 and 10.0µM, respectively.
Assuntos
Antineoplásicos/síntese química , DNA/metabolismo , Hidrazonas/química , Soroalbumina Bovina/metabolismo , Urânio/química , Antineoplásicos/farmacologia , Cristalografia por Raios X , Humanos , Simulação de Acoplamento Molecular , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Inositol 1,4,5-trisphosphate (IP(3)) is a crucial second messenger that regulates complicated signaling processes in various physiological events. Alteration in its content has been observed in many diseases. Hence, development of a high-throughput screening system to monitor temporal changes of IP(3) is essential for screening of new potential therapeutic compounds. Toward a simple, sensitive and rapid method for measuring IP(3), we describe the development and application of a novel biosensor based on luciferase fragment assisted complementation strategy, which converts the ligand-induced conformational changes to light. Designed sensor comprising the IP(3)-binding core domain of IP(3)-receptor fused between complementary non-functional fragments of firefly luciferase allows direct detection of IP(3) in presence of luciferin substrate both in cell lysate and in living cells. According to the result presented in this manuscript, the screening time was very fast and maximum response was obtained up to 11-fold higher than untreated cells. Moreover, the designed biosensor was able to monitor release of IP(3) upon induction by different inducers like Bradykinin and ATP. The current biosensor not only provides a specific IP(3) detector in vitro but also facilitates monitoring of the response of IP(3) in living organisms.