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Streptomyces sp. VN1 was isolated from the coastal region of Phu Yen Province (central Viet Nam). Morphological, physiological, and whole genome phylogenetic analyses suggested that strain Streptomyces sp. VN1 belonged to genus Streptomyces. Whole genome sequencing analysis showed its genome was 8,341,703 base pairs in length with GC content of 72.5%. Diverse metabolites, including cinnamamide, spirotetronate antibiotic lobophorin A, diketopiperazines cyclo-L-proline-L-tyrosine, and a unique furan-type compound were isolated from Streptomyces sp. VN1. Structures of these compounds were studied by HR-Q-TOF ESI/MS/MS and 2D NMR analyses. Bioassay-guided purification yielded a furan-type compound which exhibited in vitro anticancer activity against AGS, HCT116, A375M, U87MG, and A549 cell lines with IC50 values of 40.5, 123.7, 84.67, 50, and 58.64 µM, respectively. In silico genome analysis of the isolated Streptomyces sp. VN1 contained 34 gene clusters responsible for the biosynthesis of known and/or novel secondary metabolites, including different types of terpene, T1PKS, T2PKS, T3PKS, NRPS, and hybrid PKS-NRPS. Genome mining with HR-Q-TOF ESI/MS/MS analysis of the crude extract confirmed the biosynthesis of lobophorin analogs. This study indicates that Streptomyces sp. VN1 is a promising strain for biosynthesis of novel natural products.

Glioblastoma stem-like cells (GSCs) drive tumor initiation, cancer invasion, immune evasion, and therapeutic resistance and are thus a key therapeutic target for improving treatment for glioblastoma multiforme (GBM). We previously identified calcium/calmodulin-dependent protein kinase II (CaMKII) as an emerging molecular target for eliminating GSCs. In this study, we aim to explore a new CaMKII-targeted synthetic lethal therapy for GSCs. Through high-throughput drug combination screening using CaMKII inhibitors and a bioactive compound library in GSCs, neurokinin 1 receptor (NK1R) inhibitors such as SR 140333 and aprepitant are found to be potential anticancer agents that exhibit chemical synthetic lethal interactions with CaMKII inhibitors, including hydrazinobenzoylcurcumin (HBC), berbamine, and KN93. Combined treatment with NK1R and CaMKII inhibitors markedly suppresses the viability and neurosphere formation of U87MG- and U373MG-derived GSCs. In addition, the combination of HBC and NK1R inhibitors significantly inhibits U87MG GSC tumor growth in a chick embryo chorioallantoic membrane (CAM) model. Furthermore, the synthetic lethal interaction is validated using RNA interference of CaMKIIγ and NK1R. Notably, the synthetic lethal effects in GSCs are associated with the activation of caspase-mediated apoptosis by inducing p53 expression and reactive oxygen species generation, as well as the suppression of stemness marker expression by reducing nuclear factor-kappa B (NF-κB) activity. This follows the downregulation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling and a decrease in intracellular calcium concentration. Moreover, NK1R affects CaMKIIγ activation. These findings demonstrate that NK1R is a potential synthetic lethal partner of CaMKII that is involved in eradicating GSCs, and they suggest a new CaMKII-targeted combination therapy for treating GBM.

Hepatocellular carcinoma (HCC) is a malignant type of primary liver cancer with high incidence and mortality, worldwide. A major challenge in the treatment of HCC is chemotherapeutic resistance. It is therefore necessary to develop novel anticancer drugs for suppressing the growth of HCC cells and overcoming drug resistance for improving the treatment of HCC. Violacein is a deep violet-colored indole derivative that is produced by several bacterial strains, including Chromobacterium violaceum, and it possesses numerous pharmacological properties, including antitumor activity. However, the therapeutic effects of violacein and the mechanism underlying its antitumor effect against HCC remain to be elucidated. This study is the first to demonstrate that violacein inhibits the proliferation and stemness of Huh7 and Hep3B HCC cells. The antiproliferative effect of violacein was attributed to cell cycle arrest at the sub-G1 phase and the induction of apoptotic cell death. Violacein induced nuclear condensation, dissipated mitochondrial membrane potential (MMP), increased generation of reactive oxygen species (ROS), activated the caspase cascade, and upregulated p53 and p21. The anticancer effect of violacein on HCC cells was also associated with the downregulation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)1/2 signaling. Violacein not only suppressed the proliferation and formation of tumorspheres of Huh7 and Hep3B cancer stem-like cells but also reduced the expression of key markers of cancer stemness, including CD133, Sox2, Oct4, and Nanog, by inhibiting the signal transducer and activator of transcription 3 (STAT3)/AKT/ERK pathways. These results suggest the therapeutic potential of violacein in effectively suppressing HCC by targeting the proliferation and stemness of HCC cells.

A liver mass was incidentally revealed in a 10-year-old male neutered Himalayan cat on radiographic examination conducted in a local animal hospital. The abdominal distention had worsened over the past five months, along with intermittent vomiting and nausea for two weeks. Serum chemistry was unremarkable, except for elevated alkaline phosphatase and gamma-glutamyl transferase levels. Radiography revealed a round-shaped soft mass in the cranial abdomen. Abdominal ultrasonography showed a well defined, massive, fluid-filled cyst with multiple lobes, and heterogeneous echogenicity in the pancreas. Computed tomography examination revealed hypoplasia of the left lobes of the liver, but the vascular changes and enhancement of the mass were not observed on contrast computed tomography images. The herniation of the abdominal fat through the diaphragm was incidentally observed on sonography and computed tomography scan. The patient was tentatively diagnosed with pancreatic cyst. The laparotomy revealed that the origin was not related to the pancreas, but was suspended from the liver. The mass was multilobular and filled with approximately 120 ml of fluid containing a few white blood cells. The patient recovered from anesthesia, but showed postoperative respiratory depression and died of cardiac arrest 15 hours later. Histopathologically, the mass was definitively diagnosed to be hepatic cellular carcinoma.

Fabrication of hydrophobic surface with exceptional mechanical robustness has been of considerable interest for its urgent practical application. Herein, we demonstrate a facile approach to fabricate mechanically robust, hydrophobic surface by combining Al2O3, glass frits, and hydrophobic solution. Al2O3-based composite coatings with different roughness were prepared by controlling the ratio of Al2O3 particles and glass frits. Surface properties of Al2O3-based composite coatings were carefully modified by hydrophobic fluorine-containing sol-gel solution. Hydrophobic sol-gel solution-coated Al2O3-based coatings (H-Al2O3) show strong hydrophobicity, and water contact angle of 132.38° was achieved at an optimal Al2O3/glass frits ratio of 50. To demonstrate the mechanical robustness of our H-Al2O3, the hydrophobicity was evaluated after performing sandpaper (400 mesh) abrasion and ultrasonication. The H-Al2O3 still retained great water repellency even after sandpaper abrasion for 100 cm and ultrasonication for 60 min, exhibiting excellent mechanical robustness. We believed that the presented method could provide a straightforward and effective route to fabricate mechanically robust and hydrophobic surface on various substrate materials for a great number of potential applications.

Background Live fish import may lead to the unintended introduction of pathogens. We examined the monthly distribution of microbial pathogens in ornamental finfish imported into South Korea over a 6-month period. Results Vibrio alginolyticus was detected in one lemon damsel in June and July; V. vulnificus was detected in one lemon damsel, one caerulean damsel, and one pearl-spot chromis and one ocellaris clownfish in July, April, and May, respectively; Photobacterium damselae was detected in one ocellaris clownfish and one caerulean damsel in June and July, respectively; V. anguillarum was detected in one pearl-spot chromis in February; V. harveyi was detected in one ocellaris clownfish and two mandarin fish in February and April, respectively; Yersinia ruckeri was detected in a pearlscale goldfish group in June and July and in two colored carp groups in July; and Lactococcus garvieae was detected in a lemon damsel group and a sutchi catfish group in July and May, respectively. European catfish virus, the only viral pathogen detected, was found in two sutchi catfish groups in May. Conclusion This study is the first to identify pathogenic species and the presence or absence of pathogens (non-quarantine diseases) in imported ornamental finfish. These results demonstrate that various pathogens with the potential to harm indigenous fish populations can accompany ornamental finfish imported into South Korea.

Cyclophilin A (CypA), which has peptidyl–prolyl cis-trans isomerase (PPIase) activity, regulates multiple functions of cells by binding to its extracellular receptor CD147. The CypA/CD147 interaction plays a crucial role in the progression of several diseases, including inflammatory diseases, coronavirus infection, and cancer, by activating CD147-mediated intracellular downstream signaling pathways. Many studies have identified CypA and CD147 as potential therapeutic targets for cancer. Their overexpression promotes growth, metastasis, therapeutic resistance, and the stem-like properties of cancer cells and is related to the poor prognosis of patients with cancer. This review aims to understand the biology and interaction of CypA and CD147 and to review the roles of the CypA/CD147 interaction in cancer pathology and the therapeutic potential of targeting the CypA/CD147 axis. To validate the clinical significance of the CypA/CD147 interaction, we analyzed the expression levels of PPIA and BSG genes encoding CypA and CD147, respectively, in a wide range of tumor types using The Cancer Genome Atlas (TCGA) database. We observed a significant association between PPIA/BSG overexpression and poor prognosis, such as a low survival rate and high cancer stage, in several tumor types. Furthermore, the expression of PPIA and BSG was positively correlated in many cancers. Therefore, this review supports the hypothesis that targeting the CypA/CD147 interaction may improve treatment outcomes for patients with cancer.

Leukemia is a type of blood cancer caused by the rapid proliferation of abnormal white blood cells. Currently, several treatment options, including chemotherapy, radiation therapy, and bone marrow transplantation, are used to treat leukemia, but the morbidity and mortality rates of patients with leukemia are still high. Therefore, there is still a need to develop more selective and less toxic drugs for the effective treatment of leukemia. Ampelopsin, also known as dihydromyricetin, is a plant-derived flavonoid that possesses multiple pharmacological functions, including antibacterial, anti-inflammatory, antioxidative, antiangiogenic, and anticancer activities. However, the anticancer effect and mechanism of action of ampelopsin in leukemia remain unclear. In this study, we evaluated the antileukemic effect of ampelopsin against acute promyelocytic HL60 and chronic myelogenous K562 leukemia cells. Ampelopsin significantly inhibited the proliferation of both leukemia cell lines at concentrations that did not affect normal cell viability. Ampelopsin induced cell cycle arrest at the sub-G1 phase in HL60 cells but the S phase in K562 cells. In addition, ampelopsin regulated the expression of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors differently in each leukemia cell. Ampelopsin also induced apoptosis in both leukemia cell lines through nuclear condensation, loss of mitochondrial membrane potential, increase in reactive oxygen species (ROS) generation, activation of caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP), and regulation of Bcl-2 family members. Furthermore, the antileukemic effect of ampelopsin was associated with the downregulation of AKT and NF-κB signaling pathways. Moreover, ampelopsin suppressed the expression levels of leukemia stemness markers, such as Oct4, Sox2, CD44, and CD133. Taken together, our findings suggest that ampelopsin may be an attractive chemotherapeutic agent against leukemia.

We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Furthermore, compound 9 downregulated CD147-mediated mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) by inhibiting the expression of CD147, the cellular receptor of CypA. Notably, the responses of AGS cells to CypA knockdown were significantly correlated with the anticancer and antiangiogenic effects of compound 9. CypA siRNAs reduced the expression of CD147 and phosphorylation of JNK and ERK1/2. In addition, the suppressive effects of CypA siRNAs on proliferation, migration, invasion, and angiogenesis induction of AGS cells were associated with G2/M cell cycle arrest, caspase-mediated apoptosis, inhibition of MMP-9 and MMP-2 expression, inactivation of PI3K/AKT/mTOR pathway, and inhibition of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. The specific interaction between compound 9 and CypA was also confirmed using the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) approaches. Moreover, in silico docking analysis revealed that the structure of compound 9 was a good fit for the cyclosporin A binding cavity of CypA. Collectively, these findings provide a novel molecular basis for compound 9-mediated suppression of gastric cancer progression through the targeting of CypA.

Cervical cancer is the second most common cancer among women worldwide. However, chemotherapies for this cancer often cause many side effects and chemoresistance. Citrus unshiu Markovich peel (CECU) has been used as a traditional medicine for the treatment of various diseases in East Asia. Recently, the anticancer activities and mechanisms of action of CECU extract have been reported in a number of different cancer cell types, but no study has evaluated the therapeutic effect of this natural product on cervical cancer cells. In the current study, the anticancer activity and the underlying molecular mechanism of the chloroform extract of CECU was investigated on HeLa human cervical cancer cells. The results showed that CECU effectively inhibited the proliferation and migration of HeLa cells. Treatment of cells with CECU led to cell cycle arrest at the G2/M phase and activation of extrinsic and intrinsic apoptotic pathways. Furthermore, the proliferation inhibitory effect of CECU was due to the inactivation of AKT and ERK signaling, upregulation of p53 and p21, and downregulation of cyclin B1 and cyclin D1, but not reactive oxygen species (ROS) generation. Furthermore, CECU inhibited the stem‑like features of HeLa cells by downregulating key cancer stemness biomarkers. Therefore, CECU may be an effective complementary and alternative medicine for the prevention and treatment of cervical cancer.

Targeting angiogenesis is an attractive strategy for the treatment of angiogenesis-related diseases, including cancer. We previously identified 23-demethyl 8,13-deoxynargenicin (compound 9) as a novel nargenicin A1 analog with potential anticancer activity. In this study, we investigated the antiangiogenic activity and mode of action of compound 9. This compound was found to effectively inhibit in vitro angiogenic characteristics, including the proliferation, invasion, capillary tube formation, and adhesion of human umbilical vein endothelial cells (HUVECs) stimulated by vascular endothelial growth factor (VEGF). Furthermore, compound 9 suppressed the neovascularization of the chorioallantoic membrane of growing chick embryos in vivo. Notably, the antiangiogenic properties of compound 9 were related to the downregulation of VEGF/VEGFR2-mediated downstream signaling pathways, as well as matrix metalloproteinase (MMP)-2 and MMP-9 expression in HUVECs. In addition, compound 9 was found to decrease the in vitro AGS gastric cancer cell-induced angiogenesis of HUVECs by blocking hypoxia-inducible factor-1&alpha, (HIF-1&alpha, ) and VEGF expression in AGS cells. Collectively, our findings demonstrate for the first time that compound 9 is a promising antiangiogenic agent targeting both VEGF/VEGFR2 signaling in ECs and HIF-1&alpha, /VEGF pathway in tumor cells.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is a leading cause of cancer-related death worldwide. Therefore, exploring effective anticancer agents and their modes of action is essential for the prevention and treatment of HCC. Glycosylation can significantly improve the physicochemical and biological properties of small molecules, such as high solubility, stability increase, and lower toxicity. In the present study, for the first time, we evaluated the anticancer and antiangiogenic activities of &alpha, mangostin-3-O-&beta, D-2-deoxyglucopyranoside (Man-3DG) and &alpha, mangostin 6-O-&beta, D-2-deoxyglucopyranoside (Man-6DG), glycosides of &alpha, mangostin, against human HCC cells. Our results demonstrated that Man-3DG and Man-6DG significantly suppressed the growth of three different HCC cells (Hep3B, Huh7, and HepG2) as well as the migration of Hep3B cells. Furthermore, they induced cell cycle arrest in the G0/G1 phases and apoptotic cell death by regulating apoptosis-related proteins of mitochondria in Hep3B cells. Noticeably, Man-3DG and Man-6DG also caused autophagy, while co-treatment of the &alpha, mangostin glycosides with an autophagy inhibitor 3-MA enhanced the inhibitory effect on Hep3B cell growth in comparison to single agent treatment. Moreover, Man-3DG and Man-6DG inhibited the c-Met signaling pathway that plays a critical role in the pathogenesis of HCC. Furthermore, the &alpha, mangostin glycosides decreased Hep3B cell-induced angiogenesis in vitro through the downregulation of hypoxia-inducible factor-1&alpha, (HIF-1&alpha, ) and vascular endothelial growth factor (VEGF). Notably, Man-6DG more effectively inhibited the growth, tumorsphere formation, and expression of cancer stemness regulators compared to &alpha, mangostin and Man-3DG in 3D spheroid-cultured Hep3B cells. These findings suggest that the &alpha, mangostin glycosides might be promising anticancer agents for HCC treatment with superior pharmacological properties than the parent molecule &alpha, mangostin.

Cervical cancer is the second most common cancer among women worldwide. However, chemotherapies for this cancer often cause many side effects and chemoresistance. Citrus unshiu Markovich peel (CECU) has been used as a traditional medicine for the treatment of various diseases in East Asia. Recently, the anticancer activities and mechanisms of action of CECU extract have been reported in a number of different cancer cell types, but no study has evaluated the therapeutic effect of this natural product on cervical cancer cells. In the current study, the anticancer activity and the underlying molecular mechanism of the chloroform extract of CECU was investigated on HeLa human cervical cancer cells. The results showed that CECU effectively inhibited the proliferation and migration of HeLa cells. Treatment of cells with CECU led to cell cycle arrest at the G2/M phase and activation of extrinsic and intrinsic apoptotic pathways. Furthermore, the proliferation inhibitory effect of CECU was due to the inactivation of AKT and ERK signaling, upregulation of p53 and p21, and downregulation of cyclin B1 and cyclin D1, but not reactive oxygen species (ROS) generation. Furthermore, CECU inhibited the stem-like features of HeLa cells by downregulating key cancer stemness biomarkers. Therefore, CECU may be an effective complementary and alternative medicine for the prevention and treatment of cervical cancer.

Melanoma is the most serious type of skin cancer and remains highly drug-resistant. Therefore, the discovery of novel effective agents against melanoma is in high demand. Herein, we investigated the cytotoxic activities in melanoma cells and underlying molecular mechanisms of beauvericin (BEA) and its analogue beauvericin G1 (BEA G1), which are cyclohexadepsipeptides isolated from fungi. BEA and BEA G1 significantly suppressed the growth, clonogenicity, migration, and invasion of A375SM human melanoma cells and promoted caspase-dependent apoptosis through upregulation of death receptors, as well as modulation of pro- and anti-apoptotic Bcl-2 family members. Furthermore, the effects of BEA and BEA G1 were associated with the suppression of multiple molecular targets that play crucial roles in melanoma oncogenesis, including ERK, JNK, p38, NF-&kappa, B, STAT3, and MITF. Notably, the cytotoxic efficacy of BEA G1 against A375SM cells was stronger than that of BEA. These findings suggest that BEA and BEA G1 can be further investigated as potent cytotoxic natural compounds for the suppression of melanoma progression.

Nargenicin A1(1) is an antibacterial macrolide with effective activity against various Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Due to the promising properties of this compound in inhibiting cell proliferation, immunomodulation, and the cell protective effect, there has been significant interest in this molecule. Recently, the biosynthetic gene cluster (BGC) of 1 was reported from Nocardia argentinesis and Nocardia arthritidis. In addition, two crucial enzymes involved in the formation of the core decalin moiety and postmodification of the decalin moiety by an ether bridge were characterized. This study reports on the BGC of 1 from Nocardia sp. CS682. In addition, the direct capture and heterologous expression of nar BGC from Nocardia sp. CS682 in Streptomyces venezuelae led to the production of 1. Further metabolic profiling of wild type, Nocardia sp. CS682 in optimized media (DD media) resulted in the isolation of two acetylated derivatives, 18-O-acetyl-nodusmicin and 18-O-acetyl-nargenicin. The post-PKS modification pathway in biosynthesis of 1 was also deciphered by identifying intermediates and/or in vitro enzymatic reactions of NgnP1, NgnM, and NgnO3. Different novel analogues of 1, such as compound 6, compound 7, 23-demethyl 8,13-deoxy-nodusmicin (8), 23-demethyl 8,13-deoxynargenicin (9), 8,13-deoxynodusmicin (10), and 8,13-deoxynargenicin (11), were also characterized, which extended our understanding of key post-PKS modification steps during the biosynthesis of 1. In addition, the antimicrobial and anticancer activities of selected analogues were also evaluated, whereas compound 9 was shown to exhibit potent antitumor activity by induction of G2/M cell cycle arrest, apoptosis, and autophagy.

Glioblastoma multiforme (GBM) is the most aggressive and common type of human primary brain tumor. Glioblastoma stem-like cells (GSCs) have been proposed to contribute to tumor initiation, progression, recurrence, and therapeutic resistance of GBM. Therefore, targeting GSCs could be a promising strategy to treat this refractory cancer. Calmodulin (CaM), a major regulator of Ca2+ -dependent signaling, controls various cellular functions via interaction with multiple target proteins. Here, we investigated the anticancer effect of hydrazinobenzoylcurcumin (HBC), a Ca 2+ /CaM antagonist, against GSCs derived from U87MG and U373MG cells. HBC significantly inhibited not only the self-renewal capacity, such as cell growth and neurosphere formation but also the metastasis-promoting ability, such as migration and invasion of GSCs. HBC induced apoptosis of GSCs in a caspase-dependent manner. Notably, HBC repressed the phosphorylation of Ca 2+ /CaM-dependent protein kinase II (CaMKII), c-Met, and its downstream signal transduction mediators, thereby reducing the expression levels of GSC markers, such as CD133, Nanog, Sox2, and Oct4. In addition, the knockdown of CaMKIIγ remarkably decreased the cancer stem cell-like phenotypes as well as the expression of stemness markers by blocking c-Met signaling pathway in U87MG GSCs. These results suggest that HBC suppresses the stem-like features of GBM cells via downregulation of CaM/CaMKII/c-Met axis and therefore CaMKII may be a novel therapeutic target to eliminate GSCs.

The annual rate of ornamental aquatic crustacean importation is increasing globally. The continuous high demand for live ornamental aquatic crustaceans in many countries has also increased the frequency of imported exotic pathogens, which has caused many problems. In the present study, we examined the monthly distribution of viral and bacterial pathogen genes in ornamental aquatic crustaceans imported into South Korea during a 6-month period from February to July 2016. Among the bacterial pathogens identified, Vibrio alginolyticus was detected in cleaner shrimp in June, and Photobacterium damselae was detected in cleaner shrimp in July. Vibrio penaeicida was detected in peppermint shrimp, banded coral shrimp, hinge-beak shrimp, and orange swamp crayfish between February and June. Among the viral pathogens identified, spawner mortality virus was detected in cherry shrimp in May. Finally, hepatopancreatic parvovirus was detected in both cherry shrimp and orange swamp crayfish between February and March. Notably, the genes of two viral pathogens were also detected in cherry shrimp. Although the viruses were not isolated, they are very likely to have been introduced into South Korea and have an influence on Korean aquaculture. In South Korea, HPV is already prevalent and has been reported several times in aquaculture and in the wild; however, SMV infection has not been reported to date. These results demonstrate that many bacterial and viral pathogens are regularly introduced into South Korea via the ornamental aquatic-crustacean trade.

In the course of studies to discover natural products with anti-angiogenic properties, two cyclic octapeptides, octaminomycins A (1) and B (2), were isolated from the cultures of Streptomyces sp. RK85-270. Octaminomycins suppressed the vascular endothelial growth factor (VEGF)-induced proliferation, adhesion, tube formation, migration, and invasion of HUVECs. Anti-angiogenic activity was futher confirmed in vivo by the chicken chorioallantoic membrane assay. We also identified that 1 and 2 inhibited the phosphorylation of VEGF receptor 2, AKT, and ERK1/2 and the expression and activities of MMP-2 and MMP-9. These results suggest that 1 and 2 may serve as potential scaffolds for the development of therapeutic agents to angiogenesis-dependent diseases.

Organic light-emitting diode (OLED) displays are applied to various electronic devices such as smartphones and televisions in our society, replacing liquid–crystal display (LCD) due to many advantages: self-emitting property, high contrast, slimness, and flexibility. Although OLED consists mostly of organic substances, because it was developed to reduce the consumptions of rare and precious metals, OLED display has a possibility to contain more metal-based components than LCD; for instance, a pixel circuit for OLED needs two thin-film transistors (TFTs), whereas that for LCD does one. Thus, this study was intended to assess and compare possible environmental impacts due to metals in an OLED display and an LCD on a same screen size basis, to examine environmental effects of the technology transition. Hazardous waste potentials at end-of-life were examined based on metal leachability tests, and resource depletion and toxicity potentials were evaluated based on life cycle impact assessment methods. The leachability test results showed that the OLED display has higher hazardous potential than an LCD due to excessive levels of leachability for many metals under California state regulation. The OLED display had 1000–2300 times higher resource depletion potentials than the LCD due primarily to the high concentrations of gold, selenium, silver, palladium, and tin. The OLED display also had 2–600 times higher toxicity potentials due primarily to the high concentrations of arsenic, cadmium, chromium, and antimony. This study can be used to motivate waste recyclers and managers to actively collect waste OLED displays for circular economy and to direct manufactures to develop more environmental-friendly OLED displays for sustainable society. This study evaluates and compares hazardous, resource depletion, and toxic potentials from metals in a Liquid–Crystal Display (LCD) and an Organic Light-Emitting Diode (OLED) Display to examine the effect of the technology transition on environmental impacts.

Curcumin is a natural polyphenolic compound, widely acclaimed for its antioxidant, antiinflammatory, antibacterial, and anticancerous properties. However, its use has been limited due to its low-aqueous solubility and poor bioavailability, rapid clearance, and low cellular uptake. In order to assess the effect of glycosylation on the pharmacological properties of curcumin, one-pot multienzyme (OPME) chemoenzymatic glycosylation reactions with UDP- α-D-glucose or UDP-α-D-2-deoxyglucose as donor substrate were employed. The result indicated significant conversion of curcumin to its glycosylated derivatives: curcumin 4'-O-β- glucoside, curcumin 4',4''-di-O-β-glucoside, curcumin 4'-O-β-2-deoxyglucoside, and curcumin 4',4''-di-O-β-2-deoxyglucoside. The products were characterized by ultra-fast performance liquid chromatography, high-resolution quadruple-time-of-flight electrospray ionization-mass spectrometry, and NMR analyses. All the products showed improved water solubility and comparable antibacterial activities. Additionally, the curcumin 4'-O-β-glucoside and curcumin 4'-O-β-2-deoxyglucoside showed enhanced anticancer activities compared with the parent aglycone and diglycoside derivatives. This result indicates that glycosylation can be an effective approach for enhancing the pharmaceutical properties of different natural products, such as curcumin.

Ni-decorated boron (Ni/B) particles were prepared by a ball-milling method, and their physicochemical properties were fully characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDX) elemental mapping, and X-ray photoelectron spectroscopy (XPS). Upon decoration by Ni, the previously inactive boron particles showed enhanced activity in CO oxidation and photoelectrochemical hydrogen/oxygen evolution reactions (HERs/OERs). The CO oxidation onset and T10% were observed around 320 and 350°C, respectively. In preliminary tests, the Ni/B (1:3 w/w) sample showed UV and visible light current responses, and current densities of 600 and 240μA/cm2 were observed at a potential of 500mV for HER and OER, respectively. The present study emphasizes the potential application of boron as a catalyst support material for air quality control and photoelectrochemical hydrogen/oxygen evolution. Keywords: Boron, Ni-decoration, Ball-milling, CO oxidation, Hydrogen evolution, Oxygen evolution

Lysophosphatidylcholine (LPC) is a major phospholipid component of oxidized low-density lipoprotein (ox-LDL) and is implicated in its atherogenic activity. This study investigated the effects of LPC on cell viability, intracellular calcium homeostasis, and the protective mechanisms of chlorogenic acid (CGA) in human umbilical vein endothelial cells (HUVECs). LPC increased intracellular calcium ([Ca2＋]i) by releasing Ca2＋ from intracellular stores and via Ca2＋ influx through store-operated channels (SOCs). LPC also increased the generation of reactive oxygen species (ROS) and decreased cell viability. The mRNA expression of Transient receptor potential canonical (TRPC) channel 1 was increased significantly by LPC treatment and suppressed by CGA. CGA inhibited LPC-induced Ca2＋ influx and ROS generation, and restored cell viability. These results suggested that CGA inhibits SOC-mediated Ca2＋ influx and ROS generation by attenuating TRPC1 expression in LPC-treated HUVECs. Therefore, CGA might protect endothelial cells against LPC injury, thereby inhibiting atherosclerosis. [BMB Reports 2017; 50(6): 323-328].

While exploring new angiogenesis inhibitors from microbial metabolites, we recently isolated ahpatinins C, E, and G from a soil‑derived Streptomyces sp. 15JA150. Ahpatinins C, E and G are known to have pepsin and renin inhibitory activities; however, their antiangiogenic activities and underlying molecular mechanisms have not been fully elucidated. In the present study, the antiangiogenic properties of ahpatinins C, E and G were investigated. The results revealed that the natural compounds significantly inhibited the vascular endothelial growth factor (VEGF)‑induced proliferation, invasion, adhesion, and tube formation of human umbilical vein endothelial cells (HUVECs) without exhibiting any cytotoxicity. It was also revealed that ahpatinin E effectively suppressed the neovascularization of the chorioallantoic membranes in growing chick embryos. Notably, ahpatinins C, E, and G led to the downregulation of VEGF‑induced activation of VEGF receptor 2 (VEGFR2) and its downstream signaling mediators, including AKT, ERK1/2, JNK, p38, and NF‑κB, in HUVECs. Moreover, they reduced the expression of matrix metalloproteinase (MMP)‑2 and MMP‑9 in the HUVECs following stimulation with VEGF. Furthermore, ahpatinins C, E, and G reduced the tumor cell‑induced invasion and tube forming abilities of HUVECs, as well as the expression of VEGF, by suppressing hypoxia‑inducible factor‑1α (HIF‑1α) activity in U87MG glioblastoma cells. Collectively, the present findings indicated that ahpatinins C, E, and G may be used in anticancer therapy by targeting tumor angiogenesis through the inhibition of both VEGFR2 and HIF‑1α pathways.

In this study, we determined the effects of clove oil concentration and water temperature on the anesthesia and recovery times, hematological factors, and physiological responses in the olive flounder (Paralichthys olivaceus). To determine these times at three temperatures (17, 21, and 25 °C), fish (mean length [± standard deviation]: 30.0 ± 1.0 cm, mean weight [± standard deviation]: 245.0 ± 27.1 g) were exposed to clove oil at concentrations of 40, 80, 120, 160, 200, 240, and 280 mg L−1. At 0.5, 1, 3, 6, and 24 h, blood samples were collected from 10 fish in the 160 mg L−1 clove oil-treated group (AG) and the non-anesthetic group (NAG) maintained at 21 °C. Subsequently, the following parameters were analyzed: hematocrit and hemoglobin levels; red blood cell count; osmolality; cortisol, glucose, lactic acid, Na+, K+, and Cl- concentrations; and aspartate aminotransferase and alanine aminotransferase activities. Clove oil concentration and temperature exhibited interdependent effects on the anesthesia and recovery times. As the water temperature increased, the anesthesia and recovery times decreased, and as the clove oil concentration increased, the anesthesia time decreased and recovery time was prolonged. AG showed significantly higher plasma cortisol and glucose concentrations than those of NAG at 0.5 and 1 h after anesthesia, but significantly lower concentrations than those of NAG at 24 h after anesthesia. In addition, the lactic acid concentration in AG was lower than that in NAG at 0.5, 1, and 3 h. Intergroup differences for all other blood factors and osmolality were not significant before or after anesthesia. Based on stage III behavior, the anesthesia and recovery times should be less than 180 and 300 s, respectively, to prevent hypoxia in fish under anesthesia. Therefore, the stable anesthesia concentrations for olive flounder (245.0 ± 27.1 g) were 120–160 mg L−1 at 21 °C and 80–240 mg L−1 at 25 °C. Moreover, as 18–21 °C was determined to be the optimal water temperature for olive flounder rearing (˜245.0 g), we suggest that as an optimal anesthetic, clove oil can be optimally used at 160 mg L−1 concentration at 21 °C and that it is a reasonable alternative to other anesthetics. Keywords: Optimal concentration, Recovery time, Hypoxia, Hematological factor

Alizarin has been reported to have an antigenotoxic activity along with an inhibitory effect on the tumor cell growth of human colon carcinoma cells. Alizarin was biotransformed into an O-methoxide derivative using O-methyltransferase from Streptomyces avermitilis MA4680 (SaOMT2) to enhance its bioefficacy. The biotransformed product was extracted, purified, and characterized using various chromatographic and spectroscopic analyses, and confirmed to be an alizarin 2-O-methoxide. The antiproliferative activity of the compound against gastric cancer cells (AGS), uterine cervical cancer (Hela), liver cancer (HepG2), and normal cell lines was investigated. Alizarin 2-O-methoxide showed an inhibitory effect on all three cancer-cell lines at very low concentrations, from 0.078 µM, with no cytotoxicity against 267B1 (human prostate epithelial) and MRC-5 (normal human fetal lung fibroblast).

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is a leading cause of cancer-related death worldwide. Therefore, exploring effective anticancer agents and their modes of action is essential for the prevention and treatment of HCC. Glycosylation can significantly improve the physicochemical and biological properties of small molecules, such as high solubility, stability increase, and lower toxicity. In this study, for the first time, we evaluated the anticancer activities of mangostin-3-O-β-d-2-deoxyglucopyranoside (Man-3DG) and mangostin 6-O-β-d-2-deoxyglucopyranoside (Man-6DG), glycosides of mangostin, against human hepatoma Hep3B cells. Our results demonstrated that Man-3DG and Man-6DG significantly suppressed growth and migration of Hep3B cells. In addition, they induced apoptosis of Hep3B cells by regulating apoptosis-related proteins of mitochondria. Noticeably, Man-3DG and Man-6DG also caused autophage, while cotreatment of the mangostin glycosides with an autophage inhibitor 3MA enhanced the inhibitory effect on Hep3B cell growth, compared to single agent treatment. Moreover, Man-3DG and Man-6DG inhibited the c-Met signaling pathway, which plays a critical role in the pathogenesis of liver cancer. Furthermore, the mangostin glycosides decreased tumor cell-induced angiogenesis in vitro through downregulation of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). These findings suggest that Man-3DG and Man-6DG might be promising anticancer agents for HCC treatment with superior pharmacological properties than parent molecule mangostin.

A glycoside derivative of compound K (CK) was synthesized by using a glycosyltransferase, and its biological activity was tested against various cancer-cell lines. A regiospecific, β-1,4-galactosyltransferase (LgtB) converted 100% of 0.5 mmol CK into a galactosylated product in 3 h. The structure of the synthesized derivative was revealed with high performance liquid chromatography, mass spectroscopy, as well as nuclear magnetic resonance analyses, and it was recognized as 20-O-β-D-lactopyranosyl-20(S)-protopanaxadiol (CKGal). Out of the four cancer-cell lines tested (gastric carcinoma (AGS), skin melanoma (B16F10), cervical carcinoma (HeLa), and brain carcinoma (U87MG)), CKGal showed the best cytotoxic ability against B16F10 and AGS when compared to other ginsenosides like compound K (20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol), Rh2 (3-O-β-D-glucopyranosyl-20(S)-protopanaxadiol), and F12 (3-O-β-D-glucopyranosyl-12-O-β-D-glucopyranosyl-20(S)-protopanaxadiol). Thus, the synthesized derivative (CKGal) is a pharmacologically active ginsenoside.

This research attempts to study the way how the attribute of mobile network society became a certain space, based on the international hub airport. Through this, the research will show that the core characteristic of airport terminal revealed in the modern social relationship is the infrastructure integrated with architectural space. Furthermore, the study will provide whether this space can be considered as the modern public place. The increase of physical mobility and networking has not only created new sociality, but also initiated to demand space to express such social relationship. Accordingly, the urban infrastructure and architectural spaces are being produced or restructured by the society's new principles. Today's various types of transportations means and the life of endlessly being connected to internet network modifies or creates many kinds of spaces. Not only spaces that are directly related with moving or traveling such as train stations, terminals, roads, railroads, airports, hotels, streets, malls, subway stations, buses, squares, leisure complex, beach, waterside parks, or railroad parks, but also the in-between space, so called interspace, appears as an important space in life. In addition, one’s life based on such mobile technology is being transformed into ‘network membership.’ Especially, airport terminal is a modern social space where network membership is clearly shown. The world is being connected through the airport, which represents the city, and all the network created by the airport is substituting the interaction of the community. In other words, for travelers in the 21st century with mobile network, the whole world can be seen as ‘airports floating with signs.’

This study has the goal of analyzing the techniques and characteristics of urban development, after additionally constructing the high-speed railway in Japan’s Kyushu district and building a new railway station to enable the existing traditional stations accommodate with the high-speed railway. Such analysis is Received (May 4, 2016), Review Result (May 19, 2016) Accepted (May 26, 2016), Published (July 31, 2016) 31020, Assistant Professor, Ph.D., Dept. Architectural Engineering, Namseoul Univ., 91 Daehak-ro Seonghwan-eup Sebuk-gu Cheonan-si Chungcheongnam-do S.KOREA, Research Director, AUI Reserch Group, 06121, 133, Bongeunsa-ro, Gangnam-gu, Seoul, S.KOREA, email: shinyekyeong@gmail.com Co-Author) Principle Director, Ph.D., AUI Reserch Group, 06121, 133, Bongeunsa-ro, Gangnam-gu, Seoul, S.Korea, email: mcarey7878@gmail.com * 이 연구는 2011년도 한국연구재단 연구비 지원에 의한 결과의 일부임 (과제번호: 2011-0025587). A Study on the Characteristics of Urban Re-Organization regarding as an Establishment of New High-Speed Railway Stations focused on JR Kyushu's Main Stations Copyright c 2016 HSST 428 made in order to draw the conclusion of its intended (designed) meaning and attributes and to further research on finding an applicable urban development method in the domestic railway station development. The object of this study includes examples of stations renewed within the five years when Shinkansen in the Kyushu district was extended or stations which are in process of development such as Hakata station, Kumamoto station, and Kagoshima-chuo station. From the analysis of this study, the strategies are as follows.; active connecting both geographical location and function of Station, re-establishment of relation with city center and Station, establishment of close linking system for both tourist spot development, methods of Shinkansen line construction and extension a development opposite site of railway, securing the living population from high density & Mixed use development of Station Building.

Glioblastoma (GBM) is a highly malignant human brain tumor with limited treatment choices. The extremely aggressive characteristics of GBM result from GBM stem cells (GSCs), a subpopulation in tumor having self-renewal potential and resistance to chemotherapy and radiotherapy. Therefore, eliminating GSCs is an effective strategy to treat this fatal disease. In this study, we investigated the therapeutic effects of dietary flavonoids, including apigenin, quercetin, and naringenin, against cancer stem cell-like phenotypes of human GBM cell lines U87MG and U373MG. Among flavonoids studied, apigenin and quercetin significantly suppressed not only the self-renewal capacity such as cell growth and clonogenicity, but also the invasiveness of GBM stem-like cells. Notably, apigenin blocked the phosphorylation of c-Met and its downstream effectors, transducer and activator of transcription 3, AKT (Protein kinase B), and mitogen-activated protein kinase in the GSCs, thereby reducing the expression levels of GSC markers such as CD133, Nanog, and Sox2. These results suggest that the GSC inhibition effect of apigenin may be caused by downregulation of c-Met signaling pathway.

Nargenicin A1, an antibacterial produced by Nocardia sp. CS682 (KCTC 11297BP), demonstrates effective activity against various Gram-positive bacteria. Hence, we attempted to enhance nargenicin A1 production by utilizing the cumulative effect of synthetic biology, metabolic engineering and statistical media optimization strategies. To facilitate the modular assembly of multiple genes for genetic engineering in Nocardia sp. CS682, we constructed a set of multi-monocistronic vectors, pNV18L1 and pNV18L2 containing hybrid promoter (derived from ermE* and promoter region of neo r ), ribosome binding sites (RBS), and restriction sites for cloning, so that each cloned gene was under its own promoter and RBS. The multi-monocistronic vector, pNV18L2 containing transcriptional terminator showed better efficiency in reporter gene assay. Thus, multiple genes involved in the biogenesis of pyrrole moiety (ngnN2, ngnN3, ngnN4, and ngnN5 from Nocardia sp. CS682), glucose utilization (glf and glk from Zymomonas mobilis), and malonyl-CoA synthesis (accA2 and accBE from Streptomyces coelicolor A3 (2)), were cloned in pNV18L2. Further statistical optimization of specific precursors (proline and glucose) and their feeding time led to ~84.9 mg/L nargenicin from Nocardia sp. GAP, which is ~24-fold higher than Nocardia sp. CS682 (without feeding). Furthermore, pikC from Streptomyces venezuelae was expressed to generate Nocardia sp. PikC. Nargenicin A1 acid was characterized as novel derivative of nargenicin A1 produced from Nocardia sp. PikC by mass spectrometry (MS) and nuclear magnetic resonance (NMR) analyses. We also performed comparative analysis of the anticancer and antibacterial activities of nargenicin A1 and nargenicin A1 acid, which showed a reduction in antibacterial potential for nargenicin A1 acid. Thus, the development of an efficient synthetic biological platform provided new avenues for enhancing or structurally diversifying nargenicin A1 by means of pathway designing and engineering.

Malignant melanoma is one of the most aggressive skin cancer and highly resistant to most conventional treatment. In the present study, we aimed to investigate the anticancer effects and mechanisms of action of 7,8-dihydroxyflavone (7,8-DHF), a monophenolic flavone, in melanoma cells. At concentrations not exhibiting cytotoxicity, 7,8-DHF potently inhibited growth and clonogenic survival of alpha-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 melanoma cells. Furthermore, it significantly blocked migration and invasion of the metastatic melanoma cells. We also observed that 7,8-DHF exhibits anti-melanogenic activity through inhibition of tyrosinase activity in α-MSH-stimulating condition. Notably, the suppressive activities of 7,8-DHF on melanoma progression were associated with the downregulation of microphthalmia-associated transcription factor (MITF) and its main downstream transcription targets, including hypoxia-inducible factor 1α (HIF1α) and c-MET, by a decrease in cyclic adenosine monophosphate (cAMP) level. In addition, combination treatment with 7,8-DHF and resveratrol, a known therapeutic agent against melanoma, had greater anticancer activities and MITF inhibition than treatment with each single agent in α-MSH-treated B16F10 cells. Collectively, these findings may contribute to the potential application of 7,8-DHF in the prevention and treatment of malignant melanoma.