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Background Most perimenopausal and postmenopausal women experience estrogen deficiency–induced vaginal atrophy. However, estrogen replacement therapy has contraindications and side effects, which makes it unsuitable for most women. Cell-free fat extract (CEFFE) has pro-proliferative and proangiogenic tissue regeneration activities. Objectives The purpose of this study was to evaluate the effect of topical application of CEFFE in the vagina and the effect of CEFFE on vaginal keratinocytes. Methods Ovariectomized mice were treated with CEFFE via vaginal topical application for 2 weeks. The vaginal mucosal cell layer number, mucosal thickness, and vaginal collagen volume were determined by histologic analyses. Vaginal mucosa proliferation and lamina propria angiogenesis were evaluated with anti–proliferating cell nuclear antigen and anti-CD31 staining, respectively. For in vitro analysis, VK2/E6E7 cells were administered, increasing the CEFFE concentration. Cell proliferation and cell-cycle distribution were analyzed by Cell Counting Kit 8 assay and flow cytometry, respectively. Mucosal migration was evaluated with a wound-healing assay. The expression of Ki-67 and estrogen-related proteins was detected by western blotting. Results CEFFE-treated mice showed increased mucosal thickness and number of vaginal mucosal cell layers and reduced vaginal atrophy compared to ovariectomized mice. The number of proliferating cell nuclear antigen–positive cells and CD31-positive capillaries also increased. In addition, CEFFE promoted the proliferation and migration of VK2/E6E7 cells, upregulated the expression of Ki-67, and inhibited the expression of estrogen-related proteins and the PI3K/AKT pathway. Conclusions CEFFE prevents estrogen deficiency–induced vaginal atrophy by promoting vaginal mucosal proliferation and increasing neovascularization, but not through the estrogen/estrogen receptor pathway, in an ovariectomized mouse model. [ABSTRACT FROM AUTHOR]

Background: Although adipose-derived stem cells (ADSCs) and nanofat exert antiaging effects on skin, they contain cellular components that have certain limitations in clinical practice. Cell-free fat extract (Ceffe) is a fraction purified from nanofat through removal of cellular components and lipid remnants that contains various growth factors.Objectives: The purpose of this study was to evaluate the effects of Ceffe on cultured human dermal fibroblasts in vitro and on the dermis of nude mice in vivo.Methods: In the in vitro study, human dermal fibroblasts were cultured with Ceffe for 72 hours, followed by flow cytometry measurement of cell proliferation and cell cycle. In the in vivo study, different concentrations of Ceffe were injected into the dorsal skin of nude mice for 4 weeks. The thickness of the dermis; proliferation of cells; density of the capillary; and expressions of type I and III collagen (Col-1 and Col-3), matrix metalloproteinase-1, matrix metalloproteinase-3, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-3 were measured through histologic and Western blot analyses.Results: Ceffe significantly increased cell proliferation in cultured dermal fibroblasts. In the mouse skin, Ceffe significantly increased the thickness of the dermis, number of proliferating cells, density of the capillary, and expressions of Col-1 and Col-3.Conclusions: Ceffe increased the dermal thickness of nude mice, possibly by enhancing angiogenesis and extracellular matrix production, and can therefore be used for skin rejuvenation. [ABSTRACT FROM AUTHOR]

Cell-free fat extract (CEFFE), the liquid fraction derived from fat tissues, is enriched with a variety of growth factors and possesses pro-angiogenic, anti-apoptotic, and anti-oxidative properties. The aim of this study was to determine if CEFFE could accelerate chronic wound healing in mice with diabetes and investigate its underlying mechanisms. A model of circular full-thickness wound (6 mm diameter) was produced in the central dorsal region of spontaneous type 2 diabetes mellitus db/db mice. The mice were divided to three groups depending on dosage of CEFFE administered for the study; high dose CEFFE group (CEFFE high ; administered 2.5 ml/kg/day via subcutaneous injection for six days), low dose CEFFE group (CEFFE low ; administered 2.5 ml/kg/day via subcutaneous injection for three days), and a control group receiving phosphate buffer solution. Wound closure was evaluated on day 3, 7, 10, and 14 post-operation. Histological analyses, including hematoxylin-eosin staining and Masson's trichrome staining and immunohistological staining of anti-CD31 and anti-CD68, were also performed. Moreover, the effects of CEFFE on proliferation, migration, and tube formation of human immortal keratinocyte cells (HaCaT) and human vascular endothelial cells (HUVEC) were tested in vitro . The results showed that the local injection of CEFFE significantly accelerated wound healing in mice with diabetes. CEFFE improved re-epithelization and collagen secretion, promoted angiogenesis, and inhibited inflammatory macrophage infiltration in vivo . CEFFE also promoted HaCaT proliferation and migration and enhanced tubular formation in cultured HUVEC. It was concluded that CEFFE accelerates wound healing through pro-angiogenic and anti-inflammatory activities., Competing Interests: None., (AJTR Copyright © 2020.)

Combined targeted drug delivery and sustained drug release, through the application of nanomedicine, show great potential in cancer therapy and diagnostics. Systems based on folic acid conjugated with graphene oxide-based magnetic nanoparticles (NPs) show distinct advantages for such chemotherapeutic applications. Herein, we prepared FA-Fe 3 O 4 @nGO-DOX magnetic nanoparticles (MNPs) with a uniform size distribution based on nanoscale graphene oxide (nGO) encapsulated Fe 3 O 4 , which was conjugated with folic acid (FA) and loaded with doxorubicin (DOX). The prepared MNPs were characterized by various biophysical methods and featured a uniform size distribution. The uniform size of the nGO resulted in a relative narrow size distribution of the Fe 3 O 4 @nGO MNPs, which contributed to the stability of the nanocarrier system. Cell viability and in vitro biocompatibility studies of the FA-Fe 3 O 4 @nGO-DOX NPs revealed their selective uptake by MGC-803 cells. The relative viability was maintained at ∼90% after 48 h of incubation, and the hemolysis ratio confirmed the low toxicity of our modified NPs. The pH-controlled drug release and selective uptake of FA-Fe 3 O 4 @nGO NPs by MGC-803 cells via the FA receptor ensured selective killing of tumor cells. Furthermore, the nanoparticles for magnetic resonance imaging were analyzed in vitro and their signal intensity decreased as the NP concentration was increased. The nanocomposite was highly effective for in vivo imaging. Additionally, our in vivo antitumor activity and histological analysis confirmed the selective anticancer activity of the FA-Fe 3 O 4 @nGO-DOX NPs. Notably, our NPs were highly active and mice treated with FA-Fe 3 O 4 @nGO-DOX showed lower weight loss compared with mice treated with Fe 3 O 4 @nGO-DOX. More necrotic tissue was observed in the tumors of the FA-Fe 3 O 4 @nGO-DOX group compared with those observed in the control, Fe 3 O 4 @nGO-DOX, and DOX groups. Thus, FA-Fe 3 O 4 @nGO-DOX is an effective and stable candidate for targeted drug delivery.