Correction: A Bone Metastasis Nude Mouse Model Created by Ultrasound Guided Intracardiac Injection of Breast Cancer Cells: the Micro-CT, MRI and Bioluminescence Imaging Analysis.

[This corrects the article on p. 57 in vol. 64.].

Potential anti-cancer activity of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), a histone deacetylase inhibitor, against breast cancer both in vitro and in vivo.

Histone deacetylase (HDAC) is an attractive target for cancer therapy because it plays a key role in gene expression and carcinogenesis. N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) is a novel synthetic HDAC inhibitor (HDACI) that shows better pharmacological properties than a known HDACI present in the human fibrosarcoma cell: suberoylanilide hydroxamic acid (SAHA). Here, we investigate the anti-cancer activity of HNHA against breast cancer both in vitro and in vivo. HNHA arrested the cell cycle at the G(1) /S phase via p21 induction, which led to profound inhibition of cancer cell growth in vitro. In addition, HNHA-treated cells showed markedly decreased levels of VEGF and HIF-1α than SAHA and fumagillin (FUMA) when accompanied by increased histone acetylation. HNHA significantly inhibited tumor growth in an in vivo mouse xenograft model. HNHA-treated mice survived significantly longer than SAHA- and FUMA-treated mice. Dynamic MRI showed significantly decreased blood flow in the HNHA-treated mice, implying that HNHA inhibits tumor neovascularization. This finding was accompanied by marked reductions of proangiogenic factors and significant induction of angiogenesis inhibitors in tumor tissues. We have shown that HNHA is an effective anti-tumor agent in breast cancer cells in vitro and in breast cancer xenografts in vivo. Collectively, these findings indicate that HNHA may be a potent anti-cancer agent against breast cancer due to its multi-faceted inhibition of HDAC activity, as well as anti-angiogenesis activity.

Anti-inflammatory effects of Samsoeum, a Korean medicine for health insurance, on chronic bronchitis caused by lipopolysaccharide in rats.

BACKGROUND: Samsoeum (SSE), a Korean medicine, has been used to treat upper respiratory infection including residual coughs after catching a cold, and colds in patients with gastrointestinal disorder. In this study, we investigated the inhibitory effect of SSE against lipopolysaccharide (LPS)-induced bronchitis and characterized its optimal dosing range based on the improvement of SSE concentrations. MATERIALS AND METHODS: Male Sprague Dawley rats were intra-nasally administered LPS on day 0, 3 and 6. 2 g kg-1 dose of SSE for rat was determined by the human equivalent dose formula and orally administered once a day from day 3 to day 6. To clarify the optimal administration dose of SSE, various doses including 0.5 (1/4 fold), 1 (1/2 fold), 6 (3 fold), 12 (6 fold), 24 (12 fold) and 36 g kg-1 (18 fold) were also orally administered. In addition, the molecular mechanism of SSE in mucin hyperproduction was investigated in LPS-sensitized A549 cells. RESULTS: Oral administration of SSE ameliorated alveolar wall thickening and inflammatory cell infiltration of lung tissues in LPS-induced bronchitis at doses of 1/4 fold, 1/2 fold and 1 fold. The total cell and neutrophil numbers in bronchoalveolar lavage fluid (BALF) were reduced in the SSE-treated groups compared with the LPS group. In addition, 0.5, 1 and 2 g kg-1 of SSE suppressed LPS-induced mucin glycoprotein 5AC (MUC5AC) production in BALF. Furthermore, SSE treatment significantly inhibited the pro-inflammatory cytokines, resulting in the decrease of MUC5AC production by the JAK1/STAT6 signaling pathway. CONCLUSIONS: 1, 2 and 6 g kg-1 of SSE ameliorated chronic bronchitis by inhibiting LPS-induced neutrophil infiltration and MUC5AC release in BALF. These findings suggested that SSE with 0.5-3-fold of general daily intake dose would be a therapeutic agent for chronic bronchitis.

Metabotyping of rice (Oryza sativa L.) for understanding its intrinsic physiology and potential eating quality.

Rice (Oryza sativa L.), the major staple food in many countries, has genetic diversity adapted to different environmental conditions. However, metabolic traits about diverse rice plants are rarely discovered. In the present study, rice leaves and grains were collected at whole growth stages from late (LMC) and early (EMC) maturing cultivars. Metabolic dependences of rice plants on both growth and cultivar were investigated in their leaves and grains through NMR-based metabolomics approach. Rice leaf metabolome were differently regulated between two rice cultivars, thereby affecting variations of rice grain metabolome. Sucrose levels in leaves of EMC were markedly decreased compared to those in LMC, and more accumulations of sucrose, amino acids and free fatty acids were found in grains of EMC. These distinct metabolisms between EMC and LMC rice cultivars were associated with temperature during their growing seasons and might affect the eating quality of rice. The current study highlights that metabolomic approach of rice leaves and grains could lead to better understanding of the relationship between their distinct metabolisms and environmental conditions, and provide novel insights to metabolic qualities of rice grains.

Eupatilin suppresses the allergic inflammatory response in vitro and in vivo.

INTRODUCTION: Eupatilin, a pharmacologically active ingredient found in Artemisia asiatica, has been reported to have anti-oxidative, anti-inflammatory, and anti-apoptotic activities. However, molecular mechanisms underlying its anti-allergic properties are not yet clear. In this study, we investigated the effects of eupatilin on allergic inflammation in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells and a compound 48/80-induced anaphylactic shock model. METHODS: Cytokine assays, histamine assays, quantitative real-time polymerase chain reaction analysis, western blot analysis and compound 48/80-induced anaphylactic shock model were used in this study. RESULTS: Eupatilin significantly suppresses the expression and production of pro-inflammatory cytokines, such as interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6 in vitro and in vivo. In addition, eupatilin inhibits nuclear factor kappa B (NF-κB) activation by regulating the phosphorylation and degradation of IκBα via the Akt/IKK(α/ß) pathway. Eupatilin treatment also attenuates the phosphorylation of p38, ERK, and JNK MAPKs. Furthermore, eupatilin blocked anaphylactic shock and decreased the release of histamine. CONCLUSIONS: Anti-allergic inflammation may involve the expression and production of regulating pro-inflammatory cytokines via Akt/IKK(α/ß) and MAPK activation of NF-κB. On the basis of these data, eupatilin is a potential candidate for the treatment of allergic diseases.

Controlled Release of Hepatocyte Growth Factor from MPEG-b-(PCL-ran-PLLA) Diblock Copolymer for Improved Vocal Fold Regeneration.

An in situ-forming gel system comprised of diblock copolymer formed from polyethylene glycol (PEG) and polycaprolactone (PCL) {MPEG-b-(PCL-ran-PLLA)} could be used in controlled drug delivery for tissue remodeling. The purpose of this study is to demonstrate favorable vocal folds (VF) regeneration by using MPEG-b-(PCL-ran-PLLA) diblock copolymers (C97L3; CL/LA ratio 97:3) incorporating hepatocyte growth factor (HGF). Gradual release of HGF from C97L3 is detected and biochemical properties of released HGF are maintained. A scar is made with microscissors on both VFs in 32 rabbits, followed by injection of HGF-only, C97L3-only, or HGF-C97L3 composite gel in the left side VF, while the right side VF is left untreated. In vivo fluorescence live imaging system demonstrates that C97L3 enables the sustained release of injected HGF in the scarred VF for 12 weeks. The histological analysis shows increased glycosaminoglycan including hyaluronic acid accumulation and decreased collagen deposition. Videokymographic analysis shows more favorable vibrations of HGF-C97L3 treated VF mucosa, compared to other treatment groups. In conclusion, the controlled HGF release helps to regulate extracellular matrix synthesis, and leads to the eventual functional improvement of the scarred VF.

A (1)H HR-MAS NMR-Based Metabolomic Study for Metabolic Characterization of Rice Grain from Various Oryza sativa L. Cultivars.

Rice grain metabolites are important for better understanding of the plant physiology of various rice cultivars and thus for developing rice cultivars aimed at providing diverse processed products. However, the variation of global metabolites in rice grains has rarely been explored. Here, we report the identification of intra- or intercellular metabolites in rice (Oryza sativa L.) grain powder using a (1)H high-resolution magic angle spinning (HR-MAS) NMR-based metabolomic approach. Compared with nonwaxy rice cultivars, marked accumulation of lipid metabolites such as fatty acids, phospholipids, and glycerophosphocholine in the grains of waxy rice cultivars demonstrated the distinct metabolic regulation and adaptation of each cultivar for effective growth during future germination, which may be reflected by high levels of glutamate, aspartate, asparagine, alanine, and sucrose. Therefore, this study provides important insights into the metabolic variations of diverse rice cultivars and their associations with environmental conditions and genetic backgrounds, with the aim of facilitating efficient development and the improvement of rice grain quality through inbreeding with genetic or chemical modification and mutation.

Tissue-engineered artificial oesophagus patch using three-dimensionally printed polycaprolactone with mesenchymal stem cells: a preliminary report.

OBJECTIVES: There has been a recent focus on 3D printing with regard to tissue engineering. We evaluated the efficacy of a 3D-printed (3DP) scaffold coated with mesenchymal stem cells (MSCs) seeded in fibrin for the repair of partial oesophageal defects. METHODS: MSCs from rabbit bone marrow were cultured, and a 3DP polycaprolactone (PCL) scaffold was coated with the MSCs seeded in fibrin. The fibrin/MSC-coated 3DP PCL scaffold was implanted on a 5 × 10 mm artificial oesophageal defect in three rabbits (3DP/MSC group) and 3DP PCL-only scaffolds were implanted in three rabbits (3DP-only group). Three weeks post-procedure, the implanted sites were evaluated radiologically and histologically. RESULTS: None of the rabbits showed any infection, stenosis or granulation on computed tomography. In the 3DP/MSC group, the replaced scaffolds were completely covered with regenerating mucosal epithelium and smooth muscle cells as determined by haematoxylin and eosin and Desmin staining. However, mucosal epithelium and smooth muscle cell regeneration was not evident in the 3DP-only group. CONCLUSIONS: Use of the 3DP scaffold coated with MSCs seeded in fibrin resulted in successful restoration of the shape and histology of the cervical oesophagus without any graft rejection; thus, this is a promising material for use as an artificial oesophagus.

Development of a new tri-block copolymer with a functional end and its feasibility for treatment of metastatic breast cancer.

We have developed nanomedicine vehicle based on a biocompatible tri-block copolymer, poly(ethylene glycol)-block-poly(lactic acid)-block-poly(ethylene glycol) (PEG-PLA-PEG) by simple approach without toxic linker to escalate therapeutic efficacy of anticancer agent by enhanced targeting to metastasized breast cancers. The synthesized ABA type copolymer had a low polydispersity index and formed small, highly stable spherical micelles. Furthermore, a functional group at the end site of the copolymer can be decorated with imaging agents and targeting moieties. The doxorubicin loaded micelles (DLM) showed higher drug-loading capacity, faster drug release, and better cell toxicity compared to those using di-block copolymers. DLM efficiently delivered to the metastatic breast cancers in brain and bone and suppressed growing of metastasis. In demonstration of treating metastasized animal model, we present a tri-block copolymer as a potential nanomedicine vehicle to efficiently deliver anticancer drug and to effectively treat metastatic breast cancer.

Association between morningness and resilience in Korean college students.

Circadian typology and sleep quality may be essential factors associated with the promotion of resilience. However, previous studies investigating the association between circadian typology and resilience did not analyze the effects of sleep quality on resilience. Thus, the present study evaluated the association between circadian typology and resilience in Korean college students after controlling for sleep quality. Additionally, this study investigated several sleep-related variables, including sleep duration, social jetlag and sunlight exposure during the daytime, to examine the modifiable behavioral features of morningness and also investigated whether the findings regarding morningness-related modifiable habits were associated with resilience. This study included 1094 participants (947 males and 147 females) between 19 and 29 years of age (22.8 ± 1.9 years) who completed the 10-item Korean version of the Connor-Davidson Resilience Scale (CD-RISC-10), the Korean version of the Morningness-Eveningness Questionnaire (MEQ), the Pittsburgh Sleep Quality Index (PSQI), the Korean version of the Hospital Anxiety and Depression Scale (HADS) and a survey about social jetlag that determined misalignments between weekday and weekend times of awakening and activity duration under conditions of sunlight between 10:00 and 15:00. A multiple linear regression analysis revealed that sleep duration, mean daily sunlight exposure between 10:00 and 15:00 and age were positive predictors of morningness, whereas social jetlag was a negative predictor of morningness. Of these morningness-related modifiable behavioral features, mean daily sunlight exposure between 10:00 and 15:00 significantly predicted greater resilience. An additional multiple linear regression analysis revealed that morningness was a positive predictor of resilience after controlling for age, sex, depression, anxiety and sleep quality. These results support the idea that morningness and better sleep quality are associated with greater resilience. Morningness was also associated with longer sleep duration, longer sunlight exposure during the daytime and less social jetlag, whereas longer daily sunlight exposure between 10:00 and 15:00 was associated with greater resilience. Future longitudinal studies are needed to examine whether manipulations of morningness-related modifiable behavioral features can rearrange chronotype and promote resilience.

(18)F-fluoride PET imaging in a nude rat model of bone metastasis from breast cancer: Comparison with (18)F-FDG and bioluminescence imaging.

INTRODUCTION: Clinically-relevant animal models and appropriate imaging diagnostic tools are essential to study cancer and develop novel therapeutics. We evaluated a model of bone metastasis in nude rats by micro-PET and bioluminescence imaging. METHODS: A bone metastasis model was produced by intracardiac injection of osteotropic MDA-MB-231Bo-Luc human breast cancer cells into nude rats. Bioluminescence imaging and micro-PET scans using (18)F-FDG and (18)F-fluoride were acquired serially for 5 weeks. We correlated bioluminescence imaging, (18)F-FDG and (18)F-fluoride PET images, and histological slides. RESULTS: Multiple bone metastases were successfully evaluated by bioluminescence imaging and (18)F-FDG and (18)F-fluoride PET scans. Bioluminescence photon flux increased exponentially on weekly follow-up. (18)F-FDG PET revealed increased FDG uptake at the spine and bilaterally in the hind legs in week 2 images, and showed a progressive pattern up to 4 weeks that correlated with bioluminescence imaging. (18)F-fluoride PET showed minimal abnormal findings in week 2 images, but it showed an irregular pattern at the spine from week 3 or 4 images. On quantitative analysis with standardized uptake values, a pattern of gradual increase was observed from week 2 to week 4 in both (18)F-FDG PET and fluoride PET. Histopathological examination confirmed the formation of osteolytic metastasis and necrosis of the distal femur, which appeared as a photon defect on PET scans. CONCLUSION: Developing bone metastasis from breast cancer in a nude rat model was successfully evaluated with an animal PET imaging system and bioluminescence imaging. This nude rat model of bone metastasis, which can be evaluated by PET imaging, may be a valuable tool for evaluating early responses to novel therapeutics.