Spheroid-Induced Epithelial-Mesenchymal Transition Provokes Global Alterations of Breast Cancer Lipidome: A Multi-Layered Omics Analysis

Metabolic rewiring has been recognized as an important feature to the progression of cancer. However, the essential components and functions of lipid metabolic networks in breast cancer progression are not fully understood. In this study, we investigated the roles of altered lipid metabolism in the malignant phenotype of breast cancer. Using a spheroid-induced epithelial-mesenchymal transition (EMT) model, we conducted multi-layered lipidomic and transcriptomic analysis to comprehensively describe the rewiring of the breast cancer lipidome during the malignant transformation. A tremendous homeostatic disturbance of various complex lipid species including ceramide, sphingomyelin, ether-linked phosphatidylcholines, and ether-linked phosphatidylethanolamine was found in the mesenchymal state of cancer cells. Noticeably, polyunsaturated fatty acids composition in spheroid cells was significantly decreased, accordingly with the gene expression patterns observed in the transcriptomic analysis of associated regulators. For instance, the up-regulation of SCD, ACOX3, and FADS1 and the down-regulation of PTPLB, PECR, and ELOVL2 were found among other lipid metabolic regulators. Significantly, the ratio of C22:6n3 (docosahexaenoic acid, DHA) to C22:5n3 was dramatically reduced in spheroid cells analogously to the down-regulation of ELOVL2. Following mechanistic study confirmed the up-regulation of SCD and down-regulation of PTPLB, PECR, ELOVL2, and ELOVL3 in the spheroid cells. Furthermore, the depletion of ELOVL2 induced metastatic characteristics in breast cancer cells via the SREBPs axis. A subsequent large-scale analysis using 51 breast cancer cell lines demonstrated the reduced expression of ELOVL2 in basal-like phenotypes. Breast cancer patients with low ELOVL2 expression exhibited poor prognoses (HR = 0.76, CI = 0.67–0.86). Collectively, ELOVL2 expression is associated with the malignant phenotypes and appear to be a novel prognostic biomarker in breast cancer. In conclusion, the present study demonstrates that there is a global alteration of the lipid composition during EMT and suggests the down-regulation of ELOVL2 induces lipid metabolism reprogramming in breast cancer and contributes to their malignant phenotypes

NMR and GC-MS based metabolic profiling and free-radical scavenging activities of Cordyceps pruinosa mycelia cultivated under different media and light conditions.

Variation of metabolic profiles in Cordyceps pruinosa mycelia cultivated under various media and light conditions was investigated using 1H nuclear magnetic resonance (NMR) analysis and gas chromatography mass spectrometry (GC-MS) with multivariate statistical analysis. A total of 71 metabolites were identified (5 alcohols, 21 amino acids, 15 organic acids, 4 purines, 3 pyrimidines, 7 sugars, 11 fatty acids, and 5 other metabolites) by NMR and GC-MS analysis. The mycelia grown in nitrogen media and under dark conditions showed the lowest growth and ergosterol levels, essential to a functional fungal cell membrane; these mycelia, however, had the highest levels of putrescine, which is involved in abiotic stress tolerance. In contrast, mycelia cultivated in sabouraud dextrose agar with yeast extract (SDAY) media and under light conditions contained relatively higher levels of fatty acids, including valeric acid, stearic acid, lignoceric acid, myristic acid, oleic acid, palmitoleic acid, hepadecenoic acid, and linoleic acid. These mycelia also had the highest phenolic content and antioxidant activity, and did not exhibit growth retardation due to enhanced asexual development caused by higher levels of linoleic acid. Therefore, we suggested that a light-enriched environment with SDAY media was more optimal than dark condition for cultivation of C. pruinosa mycelia as biopharmaceutical or nutraceutical resources

Inhibition of MMP-2 and MMP-9 activities by solvent-partitioned Sargassum horneri extracts

Abstract Background Matrix metalloproteinases (MMPs) are linked with several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Brown seaweeds are being extensively studied for their bioactive molecule content against cancer progression. In this context, Sargassum horneri was reported to possess various bioactivities including antiviral, antimicrobial, and anti-inflammatory partly due to its phenolic compound content. Methods In this study, potential of S. horneri was evaluated through anti-MMP effect in HT1080 fibrosarcoma cells. S. horneri crude extract was fractionated with organic solvents, namely, water (H2O), n-buthanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and n-hexane. The non-toxicity of fraction samples (Sargassum horneri solvent-partitioned extracts (SHEs)) was confirmed by cell-viability assay. SHEs were tested for their ability to inhibit MMP enzymatic activity through gelatin digestion evaluation and cell migration assay. Expressions of MMP-2 and MMP-9 and tissue inhibitors of MMP (TIMPs) were evaluated by reverse transcription and Western blotting. Results All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to gelatin zymography. Except H2O fraction, fractions hindered the cell migration significantly. All tested fractions suppressed both mRNA and protein levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Conclusion Overall, current results suggested that S. horneri has potential to be a good source for anti-MMP agents, and further investigations are underway for better understanding of the action mechanism and isolation and elucidation of the bioactive molecules

Isolation and Analytical Method Validation for Phytocomponents of Aqueous Leaf Extracts from Vaccinium bracteatum Thunb. in Korea

In this study, major phytochemical compounds of Vaccinium bracteatum Thunb. (VB) aqueous leaf extract were isolated and analyzed using a HPLC-based method, followed by method validation in accordance with the International Conference on Harmonisation (ICH) guidelines for drug development. Five major compounds were isolated in VB extract. Apart from vaccinoside, which had been the only compound isolated in VB extract to date, vanillic acid and protocatechuic acid were isolated for the first time. Isolation of orientin and isoorientin in the VB extract helped validate the reverse-phase analytical method. A new simple and rapid high-performance liquid chromatography (HPLC)-based method was developed for the validation of orientin and isoorientin in VB extract and was determinated according to the ICH guidelines. The analytical method was validated through a Waters Alliance HPLC System containing an e2695 separation module and a 2998 photodiode array (PDA) detector. The VB extract and solutions of orientin and isoorientin were analyzed using a reverse-phase Eclipse XDB-C18 column (4.6 × 250 mm ID, 5 µm, Waters), which was maintained at 30 °C. A mobile phase of methanol and 0.01% formic acid in water was used at a flow rate of 1.0 mL/min to achieve gradient elution. The linearity of the orientin and isoorientin was excellent results (R2 ≥ 0.9999) in the concentration range of 1.0–50.0 μg/mL. Precision values ranged 98.55–101.70% and 98.70–101.18%, respectively. The intra-day and inter-day relative standard deviation (RSD) values of the orientin and isoorientin were all <2.0%. The average recoveries of orientin ranged 98.30–101.57%, whereas isoorientin ranged 97.81–102.14% with RSD values <2.0%. Quantitative analysis found that VB extract contained 2.90 mg/g of orientin and 3.45 mg/g of isoorientin

Organic Transistor-Based Chemical Sensors for Wearable Bioelectronics

CONSPECTUS: Bioelectronics for healthcare that monitor the health information on users in real time have stepped into the limelight as crucial electronic devices for the future due to the increased demand for "point-of-care" testing, which is defined as medical diagnostic testing at the time and place of patient care. In contrast to traditional diagnostic testing, which is generally conducted at medical institutions with diagnostic instruments and requires a long time for specimen analysis, point-of-care testing can be accomplished personally at the bedside, and health information on users can be monitored in real time. Advances in materials science and device technology have enabled next-generation electronics, including flexible, stretchable, and biocompatible electronic devices, bringing the commercialization of personalized healthcare devices increasingly within reach, e.g., wearable bioelectronics attached to the body that monitor the health information on users in real time. Additionally, the monitoring of harmful factors in the environment surrounding the user, such as air pollutants, chemicals, and ultraviolet light, is also important for health maintenance because such factors can have short- and long-term detrimental effects on the human body. The precise detection of chemical species from both the human body and the surrounding environment is crucial for personal health care because of the abundant information that such factors can provide when determining a person's health condition. In this respect, sensor applications based on an organic-transistor platform have various advantages, including signal amplification, molecular design capability, low cost, and mechanical robustness (e.g., flexibility and stretchability). This Account covers recent progress in organic transistor-based chemical sensors that detect various chemical species in the human body or the surrounding environment, which will be the core elements of wearable electronic devices. There has been considerable effort to develop high-performance chemical sensors based on organic-transistor platforms through material design and device engineering. Various experimental approaches have been adopted to develop chemical sensors with high sensitivity, selectivity, and stability, including the synthesis of new materials, structural engineering, surface functionalization, and device engineering. In this Account, we first provide a brief introduction to the operating principles of transistor-based chemical sensors. Then we summarize the progress in the fabrication of transistor-based chemical sensors that detect chemical species from the human body (e.g., molecules in sweat, saliva, urine, tears, etc.). We then highlight examples of chemical sensors for detecting harmful chemicals in the environment surrounding the user (e.g., nitrogen oxides, sulfur dioxide, volatile organic compounds, liquid-phase organic solvents, and heavy metal ions). Finally, we conclude this Account with a perspective on the wearable bioelectronics, especially focusing on organic electronic materials and devices.11sciescopu

Freshwater Biodiversity Platform (FBP): an Integrated Information Management System of Freshwater Ecosystem for the Conservation and Sustainable Use of Biodiversity

Since the Nagoya Protocol on Access to genetic resources and Benefit Sharing (ABS) came into force in 2014, the conservation and assurance of national biodiversity has been internationally stressed. The Government of South Korea is exercising significant efforts to integrate and manage the information pertaining to biological resources in line with this global trend. However, connecting and sharing biodiversity data has certain challenges because the existing databases and information systems are being operated using different standards. In the present study, we established an integrated management system for freshwater biodiversity information, the Freshwater Biodiversity Platform (FBP), to support the conservation and sustainable use of biodiversity. This platform allows the management of various types of biodiversity data, such as occurrences, habitats and genetics, for freshwater species inhabiting South Korea. The data fields are based on a global biodiversity data standard, Darwin Core, and national biodiversity standards of South Korea in order to share our data more efficiently, both nationally and internationally. It is important to note that the platform deals with information related to the utilization of biological resources as well as information representing the national biodiversity. We have collected bibliographical data, such as papers and patents, from databases, including information on the use of biological resources. The data have been refined by applying a national species list of South Korea and ontology terms in (MeSH) to compile valuable information for biological industries. Furthermore, our platform is open source and is compatible with multiple language packs to facilitate the availability of biodiversity data for other countries and institutions. Currently, the Freshwater Biodiversity Platform is being used to collect and standardize various types of existing freshwater biodiversity data to build foundations for data management. Based on these data, we will improve the platform by adding new systems that can analyze and release data for public access. This platform will provide integrated information on freshwater species from the Korean Peninsula to the world and contribute to the conservation and sustainable use of biological resources

Hyaluronate and Its Derivatives for Customized Biomedical Applications

Since hyaluronate (HA) was firstly isolated from the vitreous of bovine eyes in 1934, HA has been widely investigated for various biomedical applications. As a naturally-occurring polysaccharide, HA has been used for joint lubrication and ocular treatment in its intact form due to the excellent biocompatibility, viscoelasticity, biodegradability, and hygroscopic properties. HA can be easily functionalized via the chemical modification of its carboxyl and hydroxyl groups. Recently, a variety of biological functions of HA have been explored and a number of customized applications have been investigated taking advantages of the interaction between HA and biological tissues. HA has been used for drug delivery to enhance the blood circulation time of drugs with target-specificity to HA receptors in the body. HA has been also used to prepare tissue engineering hydrogel scaffolds for the spatiotemporal control of encapsulated cells. In this review, we describe the key biological functions of HA in the body in terms of its structure, physical properties, biodistribution and interaction with HA receptors. After that, we describe unique advantages that allow HA to be applied in various biomedical fields. Finally, we report the conventional and newly emerging applications of HA and its derivatives under commercial development stages.1114sciescopu

Sargassum miyabei Yendo Brown Algae Exert Anti-Oxidative and Anti-AdipogenicEffects on 3T3-L1 Adipocytes by Downregulating PPARγ

Background and objectives: Sargassum miyabei Yendo, belonging to the family Sargassaceae, has been reported to have various biological effects such as anti-tyrosinase activity and anti-inflammation. However, the anti-obesity effect of Sargassum miyabei Yendo has not yet been reported. Materials and Methods: The effects of Sargassum miyabei Yendo extract (SME) on 3T3-L1 adipocytes were screened by3-(4,5)-dimethylthiazo-2-yl-2,5-diphenyltetrazolium bromide (MTT), Oil red O staining, western blot, and Real-time reverse transcription polymerase chain reaction analyses. Results: Here, we show that SME had potent 2,2’-azinobis-3-ehtlbezothiazoline-6-sulfonic acid radical decolorization (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant activity with half maximal inhibitory concentration (IC50) value of 0.2868 ± 0.011 mg/mL and 0.2941 ± 0.014 mg/mL, respectively. In addition, SME significantly suppressed lipid accumulation and differentiation of 3T3-L1 preadipocytes, as shown by Oil Red O staining results. SME attenuated the expression of adipogenic- and lipogenic-related genes such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT-enhancer-binding protein alpha (C/EBPα), CCAAT-enhancer-binding protein delta (C/EBPδ), adiponectin, adipose triglyceride lipase (ATGL), fatty acid synthase (FAS), hormone-sensitive lipase (HSL), and lipoprotein lipase (LPL). Conclusions: These findings suggest that SME may have therapeutic implications for developing a new anti-obesity agent

Schematic diagram of the metabolic pathway and relative levels of the major compounds detected in <i>C. pruinosa</i> extracted with 70% MeOH and 100% <i>n-</i>hexane plus D₂O.

<p>This was modified from pathways presented in KEGG database (<a href="http://www.genome.jp/kegg/" target="_blank">http://www.genome.jp/kegg/</a>). ANOVA was performed to assess the statistical significance of differences between samples (p<0.05). Data are mean values with error bars representing standard deviation values. Different letters in bars represent the difference of statistical significance of metabolites levels. The superscript numbers in compounds represent analysis methods. 1: NMR analysis of D₂O extracts, 2: GC-MS analysis of 70% methanol extracts, 3: GC-MS analysis of n-hexane extracts.</p