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Currently, there is a great clinical demand for biocompatible and robust tissue-engineered tubular scaffolds for use as artificial vascular graft materials. Despite considerable research on vascular scaffolds, there has still been only limited development of scaffold materials possessing both sufficient mechanical strengths and biological effects for vascular application. In this work, we designed a mechanically robust, bilayered scaffold and manufactured it by combining electrospinning (ELSP) and three-dimensional (3D) printing techniques. This material was coated with polydopamine (PDA) and vascular endothelial growth factor (VEGF) was grafted directly on the scaffold surface to induce potent angiogenic activity. We confirmed that the coated-PDA layer was evenly deposited on the bare polycaprolactone (PCL) scaffold and could enable abundant VEGF immobilization with enhanced hydrophilicity. The VEGF immobilized porous tubular scaffold was well prepared without mechanical weakness induced by surface modification steps. During in vitro and in vivo testing, VEGF immobilized scaffolds elicited markedly enhanced vascular cell proliferation and angiogenic differentiation, as compared to non-treated groups. These results demonstrate that the developed scaffolds may represent an innovative paradigm in vascular tissue engineering by inducing angiogenesis as a means of remodeling and healing vascular defects for use in restorative procedures.

A bone-remodeling imbalance induced by increased bone resorption and osteoclast formation causes skeletal diseases such as osteoporosis. Induction of osteogenic differentiation of bone marrow stromal cells (BMSCs) leads to bone regeneration. Many researchers have tried to develop new adjuvants as specific stimulators of bone regeneration for therapeutic use in patients with bone resorption. We tried to develop a new adjuvant that has stronger osteogenic differentiation-promoting activity than bone morphogenetic proteins (BMPs). In this study, we identified a new peptide, which we called bone-forming peptide (BFP)-3, derived from the immature precursor of BMP-7. Upon osteogenic differentiation, BMSCs treated with BFP-3 exhibited higher alkaline phosphatase (ALP) activity and mineralization ability and significantly up-regulated expression of osteogenic genes such as ALP, osteocalcin (OC), Osterix, and Runx2 compared with control BMSCs. Furthermore, fluorescence-activated cell sorting (FACS) and immunofluorescence analyses demonstrated that BFP-3 treatment up-regulated CD44 expression. Interestingly, extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad1/5/8 phosphorylation was increased by BFP-3 treatment during osteogenic differentiation. Furthermore, BFP-3-induced osteogenic differentiation was significantly decreased by treatment with ERK1/2- and Smad-specific inhibitors. These results suggest that BFP-3 plays an important role in regulating osteogenic differentiation of BMSCs through increasing levels of osteogenic-inducing factors and regulating the ERK1/2 and Smad1/5/8 signaling pathways. Our finding indicates that BFP-3 may be a potential new therapeutic target for promoting bone formation.

Thyroid cancer is the most common endocrine malignancy and can range in severity from relatively slow-growing occult differentiated thyroid cancer to uniformly aggressive and fatal anaplastic thyroid cancer. A subset of patients with papillary thyroid cancer present with aggressive disease that is refractory to conventional treatment. Myricetin is a flavonol compound found in a variety of berries as well as walnuts and herbs. Previous studies have demonstrated that myricetin exhibits anti-cancer activity against several tumor types. However, an anti-cancer effect of myricetin against human papillary thyroid cancer (HPTC) cells has not been established. The present investigation was undertaken to gain insights into the molecular mechanism of the anti-cancer activity of myricetin against HPTC cells. We examined the cytotoxicity, DNA damaging, and cell cycle arresting activities of myricetin using SNU-790 HPTC cells. We found that myricetin exhibited cytotoxicity and induced DNA condensation in SNU-790 HPTC cells in a dose-dependent manner. Moreover, myricetin up-regulated the activation of caspase cascades and the Bax:Bcl-2 expression ratio. In addition, myricetin induced the release of apoptosis-inducing factor (AIF) and altered the mitochondrial membrane potential. Our results suggest that myricetin induces the death of SNU-790 HPTC cells and thus may prove useful in the development of therapeutic agents for human thyroid cancers.

Introduction Stress can lead to poor sleep and compromise immune function and it is important to identify approaches that can address such problems and improve quality of life. The aim of this randomized controlled trial was to examine whether aromatherapy via inhalation of essential oils could relieve perceived stress, depression, and improve sleep quality, and immune function. Methods Subjects aged 20–60 years responding to a recruitment advertisement posted in a general hospital were randomly assigned into either an aromatherapy group (n = 30) or a waiting list control group (n = 30). The subjects in the experimental treatment were asked to inhale an essential oil blend of lemon, eucalyptus, tea tree, and peppermint in a ratio of 4:2:2:1. The essential oil blend was inhaled by wearing a pendant during the day and sleeping near an aromatherapy stone at night for four weeks. Perceived stress, stress index, autonomic nervous system (ANS) activation, and glycated hemoglobin (HbA1c) levels were measured to examine stress. In addition, depression was measured using the Center for Epidemiologic Studies Depression Scale (CES-D). Sleep quality and immune state were also measured. Results The aromatherapy group had significantly lower perceived stress levels (p Conclusions In conclusion, inhalation of essential oils as per aromatherapy, resulted in lower perceived stress and depression, as well as better sleep quality, but did not influence physiological parameters, such as the stress index or immune state.

FoxO has been proposed to play a role in the promotion of insulin resistance, and inflammation. FoxO is a pro-inflammatory transcription factor that is a key mediator of generation of inflammatory cytokines such as IL-1β in the liver. However, the detailed association of FoxO6 with insulin resistance and age-related inflammation has not been fully documented. Here, we showed that FoxO6 was elevated in the livers of aging rats and obese mice that exhibited insulin resistance. In addition, virus-mediated FoxO6 activation led to insulin resistance in mice with a notable increase in PAR2 and inflammatory signaling in the liver. On the other hand, FoxO6-KO mice showed reduced PAR2 signaling with a decrease in inflammatory cytokine expression and elevated insulin signaling. Because FoxO6 is closely associated with abnormal production of IL-1β in the liver, we focused on the FoxO6/IL-1β/PAR2 axis to further examine mechanisms underlying FoxO6-mediated insulin resistance and inflammation in the liver. In vitro experiments showed that FoxO6 directly binds to and elevates IL-1β expression. In turn, IL-1β treatment elevated the protein levels of PAR2 with a significant decrease in hepatic insulin signaling, whereas PAR2-siRNA treatment abolished these effects. However, PAR2-siRNA treatment had no effect on IL-1β expression induced by FoxO6, indicating that IL-1β may not be downstream of PAR2. Taken together, we assume that FoxO6-mediated IL-1β is involved in hepatic inflammation and insulin resistance via TF/PAR2 pathway in the liver. Keywords: FoxO6, IL-1β, TF/PAR2 signaling, Aging, Inflammation, Insulin resistance

Bisphenol A (BPA) is widely used in the manufacture of plastics and epoxy resins, and is known to affect reproductive organ growth and development. However, the effects of BPA on hippocampal neurogenesis are unclear in young adult mice. Therefore, the present study was conducted to examine the effects of BPA on hippocampal neurogenesis and learning as well as memory performance in young adult mice. BPA (1, 5, and 20 mg/kg/day) was administered orally to mice for 2 weeks. It was found that high-dose BPA (20 mg/kg/day) decreased the number of newly generated cells in hippocampus, but that low-dose BPA (1 mg/kg) increased the survival of newly generated cells in hippocampi of young mice. Furthermore, high-dose BPA (20 mg/kg/day) was found to impair learning and memory performance significantly. However, no significant differences were observed between high- and low-dose treated mice in terms of levels of brain-derived neurotrophic factor (BDNF) or reactive oxygen species production in hippocampus. In addition, BPA treatment did not induce neuronal loss or damage or astrocyte activation. These data suggest that exposure to BPA causes fluctuations in hippocampal neurogenesis in young adult mice that result in spatial learning and memory impairment via a BDNF-independent pathway.