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1.
Int J Ophthalmol ; 17(6): 1028-1035, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895680

RESUMO

AIM: To evaluate the effect of auraptene (AUR) treatment in forms of free and encapsulated in niosome nanoparticles by investigating the mRNA expression level of vascular endothelium growth factor (VEGF)-A and platelet-derived growth factors (PDGFs) in human retinal pigment epithelium (RPE) cell line. METHODS: Niosome nanocarriers were produced using two surfactants Span 60 and Tween 80. RPE cell line was treated with both free AUR and niosome-encapsulated. Optimum dosage of treatments was calculated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression of VEGF-A and PDGF-A, PDGF-B, PDGF-C, PDGF-D genes was measured after total RNA extraction and cDNA synthesis, using real-time polymerase chain reaction (RT-PCR). RESULTS: The highest entrapment efficiency (EE) was achieved by Span 60:cholesterol (1:1) with 64.3%. The half maximal inhibitory concentration (IC50) of free and niosome-encapsulated AUR were 38.5 and 27.78 µg/mL, respectively. Release study revealed that niosomal AUR had more gradual delivery to the cells. RT-PCR results showed reduced expression levels of VEGF-A, PDGF-A, PDGF-B, PDGF-C, and PDGF-D after treatment with both free and niosomal AUR. CONCLUSION: Niosomal formulation of Span 60: cholesterol (1:1) is an effective drug delivery approach to transfer AUR to RPE cells. VEGF-A, PDGF-A, PDGF-B, PDGF-C, and PDGF-D are four angiogenic factors, inhibiting which by niosomal AUR may be effective in age-related macular degeneration.

2.
J Infect Chemother ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38432556

RESUMO

INTRODUCTION: Development of multi-, extensively-, and pandrug-resistant (MDR, XDR, and PDR) strains of Pseudomonas aeruginosa remains a major problem in medical care. The present study evaluated the effect of antimicrobial photodynamic therapy (aPDT) as a monotherapy and in combination with colistin against P. aeruginosa isolates. METHODS: Two P. aeruginosa isolates recovered from patients with respiratory tract infections were examined in this study. Minimum inhibitory concentration (MIC) of colistin was determined by the colistin broth disk elution (CBDE) and the reference broth microdilution (rBMD) methods. aPDT was performed using the photosensitizer (Ps) riboflavin at several concentrations and a light-emitting diode (LED) emitting blue light for different irradiation times with or without colistin at 1/2 × MIC concentration. RESULTS: Both PA1 and PA2 isolates were identified as colistin-resistant P. aeruginosa with a MIC ≥4 µg/mL by the CBDE and MICs of 512 µg/mL and 256 µg/mL, respectively, by the rBMD. In aPDT, neither riboflavin nor LED light alone had antibacterial effects. The values of colony forming units per milliliter (CFU/mL) in both isolates were significantly reduced by LED + Ps treatments in a time-dependent manner (LED irradiation time) and dose-dependent manner (Ps concentration). In comparison with control, treatment with Ps (50 µM) + LED (120 s) and Ps (100 µM) + LED (120 s) resulted in 0.27 log10 CFU/mL and 0.43 log10 CFU/mL reductions in PA1, and 0.28 log10 CFU/mL and 0.34 log10 CFU/mL reductions in PA2, respectively, (P < 0.01). The best results were obtained after the combination of aPDT followed by colistin, which increased bacterial reduction, resulting in a 0.41-0.7 log10 CFU/mL reduction for PA1 and 0.35-0.83 log10 CFU/mL reduction for PA2 (P = 0.001). CONCLUSIONS: This study suggests the potential implications of aPDT in combination with antibiotics, such as colistin for treatment of difficult-to-treat P. aeruginosa infections.

3.
Int J Ophthalmol ; 17(1): 7-15, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38239942

RESUMO

AIM: To investigate the impact of niosome nanoparticles carrying umbelliprenin (UMB), an anti-angiogenic and anti-inflammatory plant compound, on the expression of vascular endothelial growth factor (VEGF-A) and connective tissue growth factor (CTGF) genes in a human retinal pigment epithelium (RPE)-like retina-derived cell line. METHODS: UMB-containing niosomes were created, optimized, and characterized. RPE-like cells were treated with free UMB and UMB-containing niosomes. The IC50 values of the treatments were determined using an MTT assay. Gene expression of VEGF-A and CTGF was evaluated using real-time polymerase chain reaction after RNA extraction and cDNA synthesis. Niosomes' characteristics, including drug entrapment efficiency, size, dispersion index, and zeta potential were assessed. Free UMB had an IC50 of 96.2 µg/mL, while UMB-containing niosomes had an IC50 of 25 µg/mL. RESULTS: Treatment with UMB-containing niosomes and free UMB resulted in a significant reduction in VEGF-A expression compared to control cells (P=0.001). Additionally, UMB-containing niosomes demonstrated a significant reduction in CTGF expression compared to control cells (P=0.05). However, there was no significant reduction in the expression of both genes in cells treated with free UMB. CONCLUSION: Both free UMB and niosome-encapsulated UMB inhibits VEGF-A and CTGF genes expression. However, the latter demonstrates significantly greater efficacy, potentially due to the lower UMB dosage and gradual delivery. These findings have implications for anti-angiogenesis therapeutic approaches targeting age-related macular degeneration.

4.
Biol Trace Elem Res ; 201(7): 3387-3394, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36319827

RESUMO

Esophageal cancer is one of the leading causes of cancer death and the seventh most prevalent cancer worldwide. Considering the positive association of high selenium with the prevalence of esophageal cancer, we have investigated the effect of high doses of selenium on gene expression in the normal esophageal tissue of rats. Twenty male rats were randomly divided into four groups: control group, group 2 mg Se/L, 10 mg Se/L, and 20 mg Se/L rats fed with a basal basic diet and 2, 10, and 20 mg Se/L as sodium selenite in drinking water, respectively, for 20 weeks. Serum malondialdehyde and glutathione peroxidase activity were measured. Moreover, the expression and concentration of the cyclin D1, cyclin E, KRAS, p53, NF-kB, TGF-ß, and MGMT in the esophageal tissue were analyzed and compared between the four groups. In normal esophageal tissue, selenium supplementations (2, 10, and 20 mg Se/L) increased the mRNA levels of cyclin D1, P53, KRAS, NF-κB p65, and MGMT and decreased the mRNA level of TGFß1. The concentrations of cyclin D1 and MGMT were also significantly increased by selenium supplementations. Selenium supplementations had no significant effect on serum MDA but significantly increased GPX activity. The present study suggests that selenium supplementation (2, 10, and 20 mg Se/L) affects gene expression related to inflammation, Cell proliferation, and apoptosis in the normal esophageal tissue. However, there were no observed abnormalities other than reduced growth with supplementation of 20 mg/L as Na2SeO3 in rats.


Assuntos
Neoplasias Esofágicas , Selênio , Ratos , Masculino , Animais , Selênio/farmacologia , Selênio/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína Supressora de Tumor p53/genética , Glutationa Peroxidase/metabolismo , RNA Mensageiro/metabolismo , Suplementos Nutricionais , Neoplasias Esofágicas/genética , Expressão Gênica
5.
Cancer Rep (Hoboken) ; 5(11): e1716, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36147024

RESUMO

Esophageal cancer (EC) is a common malignancy with a poor prognosis worldwide. There are two core pathways that repair double-strand breaks, homologous recombination (HR) and non-homologous end joining (NHEJ) and numerous proteins are recognized that affect the occurrence of HR and NHEJ. Altered DNA damage response (DDR) pathways are associated with cancer susceptibility and affect therapeutic response and resistance in cancers. DDR pathway alterations in EC are still poorly understood. Therefore, the identification of alterations in specific genes in DDR pathways may potentially result in novel treatments for resistant cancers, especially EC. In this review, we aimed to focus on different aspects of DNA damage and repair processes in EC. Also, we reviewed new therapeutic strategies via targeting DNA repair machinery components.


Assuntos
Quebras de DNA de Cadeia Dupla , Neoplasias Esofágicas , Humanos , Reparo do DNA por Junção de Extremidades , Reparo do DNA , Dano ao DNA , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia
7.
J Liposome Res ; 30(2): 117-125, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30917715

RESUMO

Although niosomes structurally resemble liposomes, they are composed of nonionic surfactants which result in less toxicity and more stability. Here, we developed a novel niosomal formulation of I3C and investigated the nuclear translocation and activation of AhR among human acute myeloid leukaemia (AML) monocytic THP-1 cell line. Niosomal vesicles comprised of nonionic surfactants, cholesterol and I3C were prepared using thin film hydration (TFH) method and characterized according to the entrapment efficiency (EE %), size and zeta potential, by Dynamic light scattering method (DLS), and the surface morphology visualized by Transmission electron microscopy (TEM). In vitro release of I3C was evaluated and MTS assay was used to evaluate the viability of THP-1 cells. The nuclear translocation of AhR was assessed by immunocytochemistry (ICC) and Real-time RT-PCR was conducted using AhR target genes. The ratio of Cholesterol:Span 60 (1:1) niosomal formulations with the highest significant EE% were selected. I3C exerted cytotoxic effects on THP-1 cells in a dose- and time-dependent manner, while administration of niosomal I3C reduced these effects. Both niosomal and free I3C formulations facilitated the nuclear translocation of AhR. CYP1A1 was overexpressed in response to both free and niosomal I3C treatments, while IL1ß was overexpressed merely in niosomal I3C-treated THP-1 cells. Niosomal formulation of I3C resulted in reduced cytotoxicity effects by enhancing the functional effects of I3C on AhR in THP-1 cells, including its nuclear translocation and overexpression of the target genes.


Assuntos
Antineoplásicos/farmacologia , Núcleo Celular/efeitos dos fármacos , Indóis/farmacologia , Receptores de Hidrocarboneto Arílico/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Núcleo Celular/química , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/síntese química , Indóis/química , Lipossomos/síntese química , Lipossomos/química , Tamanho da Partícula , Receptores de Hidrocarboneto Arílico/química , Relação Estrutura-Atividade , Propriedades de Superfície , Tensoativos/química , Células THP-1 , Células Tumorais Cultivadas
8.
Protein Expr Purif ; 154: 147-151, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30389592

RESUMO

One of a major drawbacks correlated with expressing antibody fragments in bacterial cells is insolubility, which is often regarded as an obstacle in obtaining active molecules. Recombinant proteins aggregated as inclusion bodies within bacterial cells are thought to be unfolded or misfolded, and therefore inactive. So, denaturing and refolding strategies, which are laborious and sometime inefficient, are used to obtain correctly-folded active proteins. In the current study, we show that large quantities of correctly folded and completely active scFv molecules are there in bacterial inclusion bodies; they only need to be isolated from inclusion bodies.


Assuntos
Anticorpos Monoclonais Humanizados/química , Escherichia coli/química , Corpos de Inclusão/química , Desnaturação Proteica , Redobramento de Proteína , Proteínas Recombinantes/química
9.
J Org Chem ; 75(18): 6208-13, 2010 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-20726549

RESUMO

1,3,5-Triazo-2,4,6-triphosphorine-2,2,4,4,6,6-tetrachloride (TAPC) was found to be an efficient promoter for the oxidation of sulfides and deoxygenation of sulfoxides. Excellent yields, short reaction time, easy and quick isolation of the products, solvent-free process, and excellent chemoselectivity are the main advantages of this procedure.


Assuntos
Compostos Azo/química , Sulfetos/química , Sulfóxidos/química , Estrutura Molecular , Oxirredução , Estereoisomerismo
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