Introduction
Breast cancer is among the most prevalent mortal cancers in women worldwide. In the present study, an optimum formulation of letrozole, letrozole-loaded niosome, and empty niosome was developed, and the anticancer effect was assessed in in vitro MCF-7, MCF10A and MDA-MB-231 breast cancer cell lines.
Materials and Methods
Various niosomal formulations of letrozole were fabricated through thin-film hydration method and characterized in terms of size, polydispersity index (PDI), morphology, entrapment efficiency (EE%), release kinetics, and stability. Optimized niosomal formulation of letrozole was achieved by response surface methodology (RSM). Antiproliferative activity and the mechanism were assessed by MTT assay, quantitative real-time PCR, and flow cytometry. Furthermore, cellular uptake of optimum formulation was evaluated by confocal electron microscopy.
Results
The formulated letrozole had a spherical shape and showed a slow-release profile of the drug after 72 h. The size, PDI, and eEE% of nanoparticles showed higher stability at 4°C compared with 25°C. The drug release from niosomes was in accordance with Korsmeyer–Peppa’s kinetic model. Confocal microscopy revealed the localization of drug-loaded niosomes in the cancer cells. MTT assay revealed that all samples exhibited dose-dependent cytotoxicity against breast cancer cells. The IC
50
of mixed formulation of letrozole with letrozole-loaded niosome (L + L
3
) is the lowest value among all prepared formulations. L+L
3
influenced the gene expression in the tested breast cancer cell lines by down-regulating the expression of
Bcl
2
gene while up-regulating the expression of
p53
and
Bax
genes. The flow cytometry results revealed that L + L
3
enhanced the apoptosis rate in both MCF-7 and MDA-MB-231 cell lines compared with the letrozole (L), letrozole-loaded niosome (L
3
), and control sample.
Conclusion
Results indicated that niosomes could be a promising drug carrier for the delivery of letrozole to breast cancer cells.
Context:Vermilion lower lip cross flap is indicated for reconstruction of upper lip in residual deformities following trauma or cleft lip. Flap survival depends on incorporation of inferior labial artery in pedicle.Aims:This article reports measurement of vertical distance between inferior labial artery and vermilion surface under light microscope in midline sagittal cross-sectional specimens harvested from 22 fresh male cadavers, to design cross lip vermilion flap more accurately and reduce morbidity of donor site.Settings and Design:This study is designed to measure vertical distance between uppermost parts of inferior labial artery to vermilion surface in 22 fresh male cadavers. Tissue specimens were taken from lower lip midline in sagittal plane. Histological sections stained with Hematoxylin-eosin were reviewed by Pathologist.Materials and Methods:Measurements were done by staged micrometer which was calibrated in 10 μm subdivisions under light microscope. Vertical distance was measured in millimeter and artery location was defined as submucosal, in superficial muscle and deep muscular layer.Statistical Analysis Used:Descriptive study.Results:Analysis of data shows that mean distance was 2.42 ± 1.67 mm. In 77.27% of cases, the artery was in submucosal layer and in 13.64% of cases this artery was located in superficial muscular layer.Conclusions:As a result 4-mm depth incision of lower lip vermilion that incorporate superficial layer of orbicularis oris muscle will ensure blood supply of lower lip vermilion cross flap.
Renal ischemia-reperfusion injury (RIRI) as a pathological process induces remote organ injury such as lung complications and it is regulated in a hormone-dependent manner. This study investigates the effect of estrogen on RIR-induced pulmonary injury in ovariectomized (OV) rats. A total of 60 female Wistar rats were divided into six groups: (i) intact sham, (ii) OV sham, (iii) OV sham + estradiol valerate (E), (iv) intact ischemia, (v) OV ischemia, and (vi) OV ischemia + E. Bilateral ischemia was performed for 45 min in all groups except sham. Before the ischemia, OV groups received an intramuscular (i.m.) injection of E. After reperfusion, blood samples were collected for serum analysis and kidney and lung tissue were separated for pathological experiment and malondialdehyde (MDA) and nitrite measurement. The left lung was weighed to measure pulmonary edema. Estrogen deficiency caused a greater increase in blood urea nitrogen and creatinine levels during IRI. Ischemia reduced nitrite of serum and lung tissue. The increased level of MDA during ischemia, returned to normal levels via estrogen injection. The severity of renal and lung damage in ischemic groups increased significantly, and estrogen improved this injury. Estrogen as an antioxidant agent can reduce oxidative stress and may improve renal function and ameliorating lung damage caused by RIR.
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