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Conducting polymer (CP)-based hydrogels exhibit the behaviors of bending or contraction/relaxation due to electrical stimulation. They are similar in some ways to biological organs and have advantages regarding manipulation and miniaturization. Thus, these hydrogels have attracted considerable interest for biomedical applications. In this study, we prepared PPy/PVP hydrogel with different concentrations and content through polymerization and cross-linking induced by gamma-ray irradiation at 25 kGy to optimize the mechanical properties of the resulting PPy/PVP hydrogel. Optimization of the PPy/PVP hydrogel was confirmed by characterization using scanning electron microscopy, gel fraction, swelling ratio, and Fourier transform infrared spectroscopy. In addition, we assessed live-cell viability using live/dead assay and CCK-8 assay, and found good cell viability regardless of the concentration and content of Py/pTS. The conductivity of PPy/PVP hydrogel was at least 13 mS/cm. The mechanical properties of PPy/PVP hydrogel are important factors in their application for biomaterials. It was found that 0.15PPy/PVP20 (51.96 ± 6.12 kPa) exhibited better compressive strength than the other samples for use in CP-based hydrogels. Therefore, it was concluded that gamma rays can be used to optimize PPy/PVP hydrogel and that biomedical applications of CP-based hydrogels will be possible.Polymers 2020, 12, 111 2 of 11 due to its excellent biocompatibility and environmental stability [3,4,14]. In addition, PPy has the advantage of the range of its electrical conductivity spanning from 10 to 100 S/cm [15]. However, PPy has the disadvantage of being brittle and mechanically unstable due to its conjugated chain structure [16]. Thus, existing CP-based biomaterials have limited use in living bodies because they are too hard and brittle [4,8]. Therefore, it is necessary to develop a biomaterial by which CPs could be applied to the soft tissue of a living body. To overcome such weaknesses, CPs-based hydrogels have been actively developed [17][18][19]. The multifaceted challenge in tissue engineering is to find an ideal hydrogel prepolymer that can mimic the biology of human tissues in terms of structure, function, and performance [20]. One of the major issues in electroactive and conductive tissue engineering is the fabrication of multifunctional hydrogels with native-like biological, electrical, and mechanical properties. Therefore, the incorporation of conductive nanomaterials into hydrogels has gained substantial interest as it not only increases the electrical conductivity, but also improves the elasticity and biological activity relative to the pure hydrogel [21,22].Hydrogel is a three-dimensional network structure with a polymer chain bonded through covalent and/or secondary bonds, which enables strong hydrogen bonding with water molecules. Hydrogel can contain a large amount of water, and when in contact with water shows substantial swelling. Even so, it does not easily decompose or dissolve in water. In addition, its mechanical s...

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This study aimed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of vutiglabridin, a potential anti‐obesity treatment under development, for the first time in humans. A randomized, placebo‐controlled, single‐ and multiple‐ascending dose study (SAD and MAD, respectively) was performed in healthy Koreans and Whites. Subjects randomly received a single oral dose of 30–720 mg vutiglabridin or placebo at a ratio of 8:2 in the SAD study or 240–480 mg vutiglabridin or placebo once daily for 14 days in the MAD study. Food effect was also evaluated in 240 mg single dose group. Pharmacokinetics were evaluated through plasma concentrations, and pharmacodynamic biomarkers related to obesity or inflammation were analyzed. Safety and tolerability were assessed throughout the study. Single and multiple doses of vutiglabridin were generally well‐tolerated. The pharmacokinetic parameters show less than dose‐proportionality increase, and plasma concentrations increased more than two‐fold after multiple administrations. The mean half‐life of Koreans and Whites in the MAD study was 110 and 73 h, respectively. The systemic exposure of vutiglabridin was significantly increased when taken with a high‐fat meal, and the systemic exposure was lower in Whites than in Koreans. Vutiglabridin was well‐tolerated in healthy Koreans and Whites. The plasma concentration increased less than the dose‐proportionality manner. These results justify further investigation of vutiglabridin in patients with obesity.

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Hepatocellular carcinoma (HCC) has high fatality rate and limited therapeutic options. Here, we propose a new anti-HCC approach with high cancer-selectivity and efficient anticancer effects, based on adenovirus-mediated Tetrahymena group I trans -splicing ribozymes specifically inducing targeted suicide gene activity through HCC-specific replacement of telomerase reverse transcriptase (TERT) RNA. To confer potent anti-HCC effects and minimize hepatotoxicity, we constructed post-transcriptionally enhanced ribozyme constructs coupled with splicing donor and acceptor site and woodchuck hepatitis virus post-transcriptional regulatory element under the control of microRNA-122a (miR-122a). Adenovirus encoding post-transcriptionally enhanced ribozyme improved trans -splicing reaction and decreased human TERT (hTERT) RNA level, efficiently and selectively retarding hTERT-positive liver cancers. Adenovirus encoding miR-122a-regulated ribozyme caused selective liver cancer cytotoxicity, the efficiency of which depended on ribozyme expression level relative to miR-122a level. Systemic administration of adenovirus encoding the post-transcriptionally enhanced and miR-regulated ribozyme caused efficient anti-cancer effects at a single dose of low titers and least hepatotoxicity in intrahepatic multifocal HCC mouse xenografts. Minimal liver toxicity, tissue distribution, and clearance pattern of the recombinant adenovirus were observed in normal animals administered either systemically or via the hepatic artery. Post-transcriptionally regulated RNA replacement strategy mediated by a cancer-specific ribozyme provides a clinically relevant, safe, and efficient strategy for HCC treatment.

Endometrial stromal tumor (EST) is an uncommon and unusual mesenchymal tumor of the uterus characterized by multicolored histopathological, immunohistochemical, and molecular features. The morphology of ESTs is similar to normal endometrial stromal cells during the proliferative phase of the menstrual cycle. ESTs were first classified into benign and malignant based on the number of mitotic cells. However, recently WHO has divided ESTs into four categories: endometrial stromal nodules (ESN), undifferentiated uterine sarcoma (UUS), low-grade endometrial stromal sarcoma (LG-ESS), and high-grade endometrial stromal sarcoma (HG-ESS). HG-ESS is the most malignant of these categories, with poor clinical outcomes compared to other types. With advances in molecular biology, ESTs have been further classified with morphological identification. ESTs, including HG-ESS, is a relatively rare type of cancer, and the therapeutics are not being developed compared to other cancers. However, considering the tumor microenvironment of usual stromal cancers, the advance of immunotherapy shows auspicious outcomes reported in many different stromal tumors and non-identified uterine cancers. These studies show the high possibility of successful immunotherapy in HG-ESS patients in the future. In this review, we are discussing the background of ESTs and the BCOR and the development of HG-ESS by mutations of BCOR or other related genes. Among the gene mutations of HG-ESSs, BCOR shows the most common mutations in different ways. In current tumor therapies, immunotherapy is one of the most effective therapeutic approaches. In order to connect immunotherapy with HG-ESS, the understanding of tumor microenvironment (TME) is required. The TME of HG-ESS shows the mixture of tumor cells, vessels, immune cells and non-malignant stromal cells. Macrophages, neutrophils, dendritic cells and natural killer cells lose their expected functions, but rather show pro-tumoral functions by the matricellular proteins, extracellular matrix and other complicated environment in TME. In order to overcome the current therapeutic limitations of HG-ESS, immunotherapies should be considered in addition to the current surgical strategies. Checkpoint inhibitors, cytokine-based immunotherapies, immune cell therapies are good candidates to be considered as they show promising results in other stromal cancers and uterine cancers, while less studied because of the rarity of ESTs. Based on the advance of knowledge of immune therapies in HG-ESS, the new strategies can also be applied to the current therapies and also in other ESTs.