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1.
Int J Mol Sci ; 25(7)2024 Mar 24.
Article in English | MEDLINE | ID: mdl-38612446

ABSTRACT

Camellia is an important plant genus that includes well-known species such as C. sinensis, C. oleifera, and C. japonica. The C. sinensis cultivar 'Sangmok', one of Korea's standard types of tea landraces, is a small evergreen tree or shrub. Genome annotation has shown that Korean tea plants have special and unique benefits and superior components, such as catechin. The genome of Camellia sinensis cultivar 'Sangmok' was assembled on the chromosome level, with a length of 2678.62 Mbp and GC content of 38.16%. Further, 15 chromosome-scale scaffolds comprising 82.43% of the assembly (BUSCO completeness, 94.3%) were identified. Analysis of 68,151 protein-coding genes showed an average of 5.003 exons per gene. Among 82,481 coding sequences, the majority (99.06%) were annotated by Uniprot/Swiss-Prot. Further analysis revealed that 'Sangmok' is closely related to C. sinensis, with a divergence time of 60 million years ago. A total of 3336 exclusive gene families in 'Sangmok' were revealed by gene ontology analysis to play roles in auxin transport and cellular response mechanisms. By comparing these exclusive genes with 551 similar catechin genes, 17 'Sangmok'-specific catechin genes were identified by qRT-PCR, including those involved in phytoalexin biosynthesis and related to cytochrome P450. The 'Sangmok' genome exhibited distinctive genes compared to those of related species. This comprehensive genomic investigation enhances our understanding of the genetic architecture of 'Sangmok' and its specialized functions. The findings contribute valuable insights into the evolutionary and functional aspects of this plant species.


Subject(s)
Camellia sinensis , Catechin , Humans , Secondary Metabolism , Exons , Chromosomes, Human, Pair 15 , Camellia sinensis/genetics , Tea
2.
Biopharm Drug Dispos ; 44(5): 365-371, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37448189

ABSTRACT

Suberosin is a natural phytoconstituent isolated from Citropsis articulata, especially employed for its anticoagulant properties. Although metabolic studies assessing suberosin have been conducted, it is possible interactions with drugs and food have not yet been investigated. In the present study, we analyzed the selective inhibitory effects of suberosin on cytochrome P450 (CYP) enzymes using a cocktail probe assay. Various concentrations of suberosin (0-50 µM) were incubated with isoform-specific CYP probes in human liver microsomes (HLMs). We found that suberosin significantly inhibited CYP1A2-catalyzed phenacetin O-deethylation, exhibiting IC50 values of 9.39 ± 2.05 and 3.07 ± 0.45 µM with and without preincubation in the presence of ß-NADPH, respectively. Moreover, suberosin showed concentration-dependent, but not time-dependent, CYP1A2 inhibition in HLMs, indicating that suberosin acts as a substrate and reversible CYP1A2 inhibitor. Using a Lineweaver-Burk plot, we found that suberosin competitively inhibited CYP1A2-catalyzed phenacetin O-deethylation. Furthermore, suberosin showed similar inhibitory effects on recombinant human CYP1A1 and 1A2. In conclusion, suberosin may elicit herb-drug interactions by selectively inhibiting CYP1A2 during the concurrent administration of drugs that act as CYP1A2 substrates.


Subject(s)
Cytochrome P-450 CYP1A2 , Microsomes, Liver , Humans , Cytochrome P-450 CYP1A2/metabolism , Cytochrome P-450 CYP1A2/pharmacology , Microsomes, Liver/metabolism , Cytochrome P-450 Enzyme Inhibitors/pharmacology , Phenacetin/pharmacology , Phenacetin/metabolism , Cytochrome P-450 Enzyme System/metabolism
3.
Int J Mol Sci ; 23(7)2022 Mar 27.
Article in English | MEDLINE | ID: mdl-35409041

ABSTRACT

Anthocyanins are generally accumulated within a few layers, including the epidermal cells of leaves and stems in plants. Solanum tuberosum cv. 'Jayoung' (hereafter, JY) is known to accumulate anthocyanin both in inner tissues and skins. We discovered that anthocyanin accumulation in the inner tissues of JY was almost diminished (more than 95% was decreased) in tuber induction condition. To investigate the transcriptomic mechanism of anthocyanin accumulation in JY flesh, which can be modulated by growth condition, we performed mRNA sequencing with white-colored flesh tissue of Solanum tuberosum cv. 'Atlantic' (hereafter, 'Daeseo', DS) grown under canonical growth conditions, a JY flesh sample grown under canonical growth conditions, and a JY flesh sample grown under tuber induction conditions. We could identify 36 common DEGs (differentially expressed genes) in JY flesh from canonical growth conditions that showed JY-specifically increased or decreased expression level. These genes were enriched with flavonoid biosynthetic process terms in GO analysis, as well as gene set enrichment analysis (GSEA) analysis. Further in silico analysis on expression levels of anthocyanin biosynthetic genes including rate-limiting genes such as StCHS and StCHI followed by RT-PCR and qRT-PCR analysis showed a strong positive correlation with the observed phenotypes. Finally, we identified StWRKY44 from 36 common DEGs as a possible regulator of anthocyanin accumulation, which was further supported by network analysis. In conclusion, we identified StWRKY44 as a putative regulator of tuber-induction-dependent anthocyanin accumulation.


Subject(s)
Anthocyanins , Solanum tuberosum , Gene Expression Profiling , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Solanum tuberosum/genetics , Solanum tuberosum/metabolism , Transcriptome
4.
Sci Rep ; 12(1): 997, 2022 01 19.
Article in English | MEDLINE | ID: mdl-35046506

ABSTRACT

Mental imagery is an important tool in the cognitive control of emotion. The present study tests the prediction that visual imagery can generate and regulate differential fear conditioning via the activation and prioritization of stimulus representations in early visual cortices. We combined differential fear conditioning with manipulations of viewing and imagining basic visual stimuli in humans. We discovered that mental imagery of a fear-conditioned stimulus compared to imagery of a safe conditioned stimulus generated a significantly greater conditioned response as measured by self-reported fear, the skin conductance response, and right anterior insula activity (experiment 1). Moreover, mental imagery effectively down- and up-regulated the fear conditioned responses (experiment 2). Multivariate classification using the functional magnetic resonance imaging data from retinotopically defined early visual regions revealed significant decoding of the imagined stimuli in V2 and V3 (experiment 1) but significantly reduced decoding in these regions during imagery-based regulation (experiment 2). Together, the present findings indicate that mental imagery can generate and regulate a differential fear conditioned response via mechanisms of the depictive theory of imagery and the biased-competition theory of attention. These findings also highlight the potential importance of mental imagery in the manifestation and treatment of psychological illnesses.


Subject(s)
Conditioning, Classical , Fear/psychology , Imagination , Adult , Electric Stimulation , Female , Galvanic Skin Response , Humans , Magnetic Resonance Imaging/methods , Male
5.
Nat Commun ; 11(1): 5875, 2020 11 18.
Article in English | MEDLINE | ID: mdl-33208749

ABSTRACT

Senna tora is a widely used medicinal plant. Its health benefits have been attributed to the large quantity of anthraquinones, but how they are made in plants remains a mystery. To identify the genes responsible for plant anthraquinone biosynthesis, we reveal the genome sequence of S. tora at the chromosome level with 526 Mb (96%) assembled into 13 chromosomes. Comparison among related plant species shows that a chalcone synthase-like (CHS-L) gene family has lineage-specifically and rapidly expanded in S. tora. Combining genomics, transcriptomics, metabolomics, and biochemistry, we identify a CHS-L gene contributing to the biosynthesis of anthraquinones. The S. tora reference genome will accelerate the discovery of biologically active anthraquinone biosynthesis pathways in medicinal plants.


Subject(s)
Anthraquinones/metabolism , Genome, Plant , Plant Proteins/genetics , Senna Plant/metabolism , Anthraquinones/chemistry , Biosynthetic Pathways , Chromosomes, Plant/genetics , Chromosomes, Plant/metabolism , Plant Proteins/metabolism , Senna Plant/chemistry , Senna Plant/genetics
6.
Fitoterapia ; 146: 104724, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32946945

ABSTRACT

Particulate matter with an aerodynamic diameter equal to or less than 2.5 µm (PM2.5) is a form of air pollutant that causes significant lung damage when inhaled. Cardamonin, a flavone found in Alpinia katsumadai Heyata seeds, has been reported to have anti-inflammatory and anticoagulative activity. The aim of this study was to determine the protective effects of cardamonin on PM2.5-induced lung injury. Mice were treated with cardamonin via tail-vein injection 30 min after the intratracheal instillation of PM2.5. The results showed that cardamonin markedly reduced the pathological lung injury, lung wet/dry weight ratio, and hyperpermeability caused by PM2.5. Cardamonin also significantly inhibited PM2.5-induced myeloperoxidase (MPO) activity in lung tissue, decreased the levels of PM2.5-induced inflammatory cytokines and effectively attenuated PM2.5-induced increases in the number of lymphocytes in the bronchoalveolar lavage fluid (BALF). And, cardamonin increased the phosphorylation of mammalian target of rapamycin (mTOR) and dramatically suppressed the PM2.5-stimulated expression of toll-like receptor 2 and 4 (TLR 2,4), MyD88, and the autophagy-related proteins LC3 II and Beclin 1. In conclusion, these findings indicate that cardamonin has a critical anti-inflammatory effect due to its ability to regulate both the TLR2,4-MyD88 and mTOR-autophagy pathways and may thus be a potential therapeutic agent against PM2.5-induced lung injury.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Autophagy , Chalcones/therapeutic use , Lung Injury/drug therapy , Particulate Matter/adverse effects , Signal Transduction , Animals , Bronchoalveolar Lavage Fluid/cytology , Cells, Cultured , Cytokines/metabolism , Endothelial Cells/drug effects , Lung Injury/chemically induced , Male , Mice , Mice, Inbred BALB C , TOR Serine-Threonine Kinases/metabolism , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism
7.
Xenobiotica ; 50(12): 1423-1433, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32654586

ABSTRACT

Hydrocoptisonine is a new compound that has been isolated from the rhizomes of Coptis chinensis, which belongs to the Ranunculaceae family of Chinese medicines. Although studies on C. chinensis have been reported, the metabolic pathway of hydrocoptisonine in human liver microsomes (HLMs) remains unelucidated. We identified 13 metabolites in HLMs, including six Phase I metabolites and seven glucuronide conjugates, using a high-resolution quadrupole-orbitrap mass spectrometer. The major metabolic pathway was the O-demethylation and mono-hydroxylation of hydrocoptisonine in HLMs. Notably, M3 metabolite was O-demethylated in dioxolane structures (cyclohexa-3,5-diene-1,2-dione), which was mediated by cytochrome P450 1A2. The locations of hydroxylation and hydroxyl-glucuronidation were identified by analyzing the signature fragments generated as a result of tandem mass spectrometry, indicating hydroxylation at an aliphatic chain or aromatic ring. We determined whether the hydroxylation and glucuronidation occurred in an aromatic moiety (M5 and M12) or an aliphatic moiety (M6 and M13), respectively, based on signature fragments of the metabolites.


Subject(s)
Drugs, Chinese Herbal/metabolism , Microsomes, Liver/metabolism , Cytochrome P-450 CYP1A2 , Glucuronides/metabolism , Humans , Hydroxylation , Metabolic Networks and Pathways , Tandem Mass Spectrometry
8.
Phytomedicine ; 69: 153200, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32163831

ABSTRACT

BACKGROUND: Maslinic acid (MA), a natural triterpenoid from Olea europaea, prevents oxidative stress and pro-inflammatory cytokine generation. High mobility group box 1 (HMGB1) has been recognized as a late mediator of sepsis, and the inhibition of the release of HMGB1 and the recovery of vascular barrier integrity have emerged as attractive therapeutic strategies for the management of sepsis. METHODS: We tested the hypothesis that MA induces sirtuin 1 and heme oxygenase-1, which inhibit the release of HMGB1 in lipopolysaccharide (LPS)-stimulated cells, thus inhibiting HMGB1-induced hyperpermeability and increasing the survival of septic mice. MA was administered after LPS or HMGB1 challenge, and the antiseptic activity of MA was determined based on permeability, the activation of pro-inflammatory proteins, and the production of markers for tissue injury in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and a cecal ligation and puncture (CLP)-induced sepsis mouse model. RESULTS: MA significantly reduced the release of HMGB1 in LPS-activated HUVECs and attenuated the CLP-induced release of HMGB1. Additionally, MA alleviated HMGB1-mediated vascular disruption and inhibited hyperpermeability in mice, and in vivo analysis revealed that MA reduced sepsis-related mortality and tissue injury. CONCLUSION: Taken together, the present results suggest that MA reduced HMGB1 release and septic mortality and thus may be useful in the treatment of sepsis.


Subject(s)
HMGB1 Protein/metabolism , Sepsis/drug therapy , Triterpenes/pharmacology , Animals , Cell Adhesion/drug effects , Cytokines/metabolism , Disease Models, Animal , Heme Oxygenase-1/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Lipopolysaccharides/toxicity , Male , Mice, Inbred C57BL , Neutrophils/drug effects , Sepsis/metabolism , Sepsis/mortality , Sepsis/pathology , Sirtuin 1/metabolism
9.
Biochem Biophys Res Commun ; 508(1): 102-108, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30471851

ABSTRACT

The NSD family (NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1) are histone lysine methyltransferases (HMTases) essential for chromatin regulation. The NSDs are oncoproteins, drivers of a number of tumors and are considered important drug-targets but the lack of potent and selective inhibitors hampers further therapeutic development and limits exploration of their biology. In particular, MMSET/NSD2 selective inhibition is being pursued for therapeutic interventions against multiple myeloma (MM) cases, especially in multiple myeloma t(4;14)(p16.3;q32) translocation that is associated with a significantly worse prognosis than other MM subgroups. Multiple myeloma is the second most common hematological malignancy, after non-Hodgkin lymphoma and remains an incurable malignancy. Here we report the discovery of LEM-14, an NSD2 specific inhibitor with an in vitro IC50 of 132 µM and that is inactive against the closely related NSD1 and NSD3. LEM-14-1189, a LEM-14 derivative, differentially inhibits the NSDs with in vitro IC50 of 418 µM (NSD1), IC50 of 111 µM (NSD2) and IC50 of 60 µM (NSD3). We propose LEM-14 and derivative LEM-14-1189 as tools for studying the biology of the NSDs and constitute meaningful steps toward potent NSDs therapeutic inhibitors.


Subject(s)
Enzyme Inhibitors/pharmacology , Histone-Lysine N-Methyltransferase/antagonists & inhibitors , Oncogene Proteins/antagonists & inhibitors , Repressor Proteins/antagonists & inhibitors , Catalytic Domain , Drug Design , Drug Discovery , Drug Evaluation, Preclinical , Enzyme Inhibitors/chemistry , Histone-Lysine N-Methyltransferase/chemistry , Histone-Lysine N-Methyltransferase/genetics , Humans , Kinetics , Models, Molecular , Molecular Docking Simulation , Molecular Structure , Protein Conformation , Repressor Proteins/chemistry , Repressor Proteins/genetics , User-Computer Interface
10.
Nat Prod Res ; 33(12): 1705-1712, 2019 Jun.
Article in English | MEDLINE | ID: mdl-29382223

ABSTRACT

The methanol extract of Abronia nana suspension cultures were subjected to column chromatography to identify potential inhibitors of ß-secretase, which is a major factor in Alzheimer's disease development. Two new C-methylisoflavones boeravinone T (1) and U (4) were isolated with three knowns boeravinone B (2), J (3) and X (5). The half-maximal inhibitory concentration (IC50) values of compounds 1-5 were 18.29, 8.57, 7.87, 12.02 and 5.30 µM, respectively. The most potent 5, non-competitively inhibited ß-secretase [inhibition constant (Ki) = 3.79 µM]. Compounds 1-5 did not inhibit other proteases such as chymotrypsin, trypsin and elastase at concentrations up to 1 mM, indicating that they were relatively specific inhibitors of ß-secretase. A free hydroxyl group at C-3 position of the C-methylisoflavone skeleton appeared to be responsible for the stronger inhibitory activity against ß-secretase.


Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Nyctaginaceae/chemistry , Alzheimer Disease/etiology , Benzopyrans/isolation & purification , Benzopyrans/pharmacology , Flavonoids/isolation & purification , Flavonoids/pharmacology , Humans , Inhibitory Concentration 50 , Plant Extracts/chemistry , Plant Extracts/pharmacology , Structure-Activity Relationship , Substrate Specificity
11.
PLoS One ; 13(12): e0208344, 2018.
Article in English | MEDLINE | ID: mdl-30533012

ABSTRACT

Adlay (Coix lacryma-jobi) is a tropical grass that has long been used in traditional Chinese medicine and is known for its nutritional benefits. Recent studies have shown that vitamin E compounds in adlay protect against chronic diseases such as cancer and heart disease. However, the molecular basis of adlay's health benefits remains unknown. Here, we generated adlay gene sets by de novo transcriptome assembly using long-read isoform sequencing (Iso-Seq) and short-read RNA-Sequencing (RNA-Seq). The gene sets obtained from Iso-seq and RNA-seq contained 31,177 genes and 57,901 genes, respectively. We confirmed the validity of the assembled gene sets by experimentally analyzing the levels of prolamin and vitamin E biosynthesis-associated proteins in adlay plant tissues and seeds. We compared the screened adlay genes with known gene families from closely related plant species, such as rice, sorghum and maize. We also identified tissue-specific genes from the adlay leaf, root, and young and mature seed, and experimentally validated the differential expression of 12 randomly-selected genes. Our study of the adlay transcriptome will provide a valuable resource for genetic studies that can enhance adlay breeding programs in the future.


Subject(s)
Coix/genetics , Sequence Analysis, RNA/methods , Transcriptome/genetics , Coix/metabolism , Prolamins/metabolism , Protein Isoforms/genetics , Sorghum/genetics , Vitamin E/metabolism , Zea mays/genetics
12.
Plant Biotechnol J ; 16(11): 1904-1917, 2018 11.
Article in English | MEDLINE | ID: mdl-29604169

ABSTRACT

Panax ginseng C. A. Meyer, reputed as the king of medicinal herbs, has slow growth, long generation time, low seed production and complicated genome structure that hamper its study. Here, we unveil the genomic architecture of tetraploid P. ginseng by de novo genome assembly, representing 2.98 Gbp with 59 352 annotated genes. Resequencing data indicated that diploid Panax species diverged in association with global warming in Southern Asia, and two North American species evolved via two intercontinental migrations. Two whole genome duplications (WGD) occurred in the family Araliaceae (including Panax) after divergence with the Apiaceae, the more recent one contributing to the ability of P. ginseng to overwinter, enabling it to spread broadly through the Northern Hemisphere. Functional and evolutionary analyses suggest that production of pharmacologically important dammarane-type ginsenosides originated in Panax and are produced largely in shoot tissues and transported to roots; that newly evolved P. ginseng fatty acid desaturases increase freezing tolerance; and that unprecedented retention of chlorophyll a/b binding protein genes enables efficient photosynthesis under low light. A genome-scale metabolic network provides a holistic view of Panax ginsenoside biosynthesis. This study provides valuable resources for improving medicinal values of ginseng either through genomics-assisted breeding or metabolic engineering.


Subject(s)
Genome, Plant/genetics , Panax/genetics , Adaptation, Biological/genetics , Biological Evolution , Diploidy , Genes, Chloroplast/genetics , Genes, Plant/genetics , Ginsenosides/biosynthesis , Panax/metabolism , Tetraploidy
13.
J Sep Sci ; 41(12): 2517-2527, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29607619

ABSTRACT

Papaver plants can produce diverse bioactive alkaloids. Papaver rhoeas Linnaeus (common poppy or corn poppy) is an annual flowering medicinal plant used for treating cough, sleep disorder, and as a sedative, pain reliever, and food. It contains various powerful alkaloids like rhoeadine, benzylisoquinoline, and proaporphine. To investigate and identify alkaloids in the aerial parts of P. rhoeas, samples were collected at different growth stages and analyzed using liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. A liquid chromatography with mass spectrometry method was developed for the identification and metabolite profiling of alkaloids for P. rhoeas by comparing with Papaver somniferum. Eighteen alkaloids involved in benzylisoquinoline alkaloid biosynthesis were used to optimize the liquid chromatography gradient and mass spectrometry conditions. Fifty-five alkaloids, including protoberberine, benzylisoquinoline, aporphine, benzophenanthridine, and rhoeadine-type alkaloids, were identified authentically or tentatively by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry in samples taken during various growth stages. Rhoeadine alkaloids were observed only in P. rhoeas samples, and codeine and morphine were tentatively identified in P. somniferum. The liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry method can be a powerful tool for the identification of diverse metabolites in the genus Papaver. These results may help understand the biosynthesis of alkaloids in P. rhoeas and evaluate the quality of this plant for possible medicinal applications.


Subject(s)
Alkaloids/chemistry , Chromatography, Liquid/methods , Papaver/chemistry , Plant Extracts/chemistry , Tandem Mass Spectrometry/methods , Plant Components, Aerial/chemistry , Plants, Medicinal/chemistry
14.
J Microbiol Biotechnol ; 28(2): 246-254, 2018 Feb 28.
Article in English | MEDLINE | ID: mdl-29169218

ABSTRACT

Enzyme fermentation is a type of food processing technique generally used to improve the biological activities of food and herbal medicines. In this study, a Syzygii Flos (clove) extract was fermented using laccase derived from Trametes versicolor (LTV). The fermented clove extract showed greater neuroprotective effects against glutamate toxicity on HT22 than the non-fermented extract did. HPLC analysis revealed that the eugenol (1) and dehydrodieugenol (2) contents had decreased and increased, respectively, after fermentation. The content of 2 peaked at 1 h after fermentation to 103.50 ± 8.20 mg/gex (not detected at zero time), while that of 1 decreased to 79.54 ± 4.77 mg/gex (185.41 ± 10.16 mg/gex at zero time). Compound 2 demonstrated promising HT22 neuroprotective properties with inhibition of Ca2+ influx, the overproduction of intracellular reactive oxygen species, and lipid peroxidation. In addition, LTV showed the best fermentation efficacy compared with laccases derived from Pleurotus ostreatus and Rhus vernicifera.


Subject(s)
Eugenol/analogs & derivatives , Fermentation , Glutamic Acid/toxicity , Laccase/metabolism , Lignans/metabolism , Lignans/pharmacology , Plant Extracts/metabolism , Plant Extracts/pharmacology , Syzygium/chemistry , Animals , Cell Death/drug effects , Cell Line/drug effects , Cell Survival/drug effects , Eugenol/chemistry , Eugenol/metabolism , Eugenol/pharmacology , Fungal Proteins/metabolism , Lignans/chemistry , Lipid Peroxidation , Mice , Plants, Medicinal , Pleurotus/enzymology , Pleurotus/metabolism , Rats , Reactive Oxygen Species , Republic of Korea , Rhus/enzymology , Rhus/metabolism , Trametes/enzymology , Trametes/metabolism
15.
Bioresour Technol ; 234: 432-438, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28347963

ABSTRACT

Two competitive strategies, fed-batch and sequencing-batch cultivation, were compared in cost-effective biomass production of a high lipid microalgae, Micractinium inermum NLP-F014 using a blended wastewater medium. For fed-batch cultivations, additional nutrient was supplemented at day 2 (FB1) or consecutively added at day 2 and 4 (FB2). Through inoculum size test, 1.0g-DCWL-1 was selected for the sequencing-batch cultivation (SB) where about 65% of culture was replaced with fresh medium every 2days. Both fed-batch cultivations showed the maximum biomass productivity of 0.95g-DCWL-1d-1, while average biomass productivity in SB was slightly higher as 0.96±0.08g-DCWL-1d-1. Furthermore, remained concentrations of organics (426mg-CODL-1), total nitrogen (15.4mg-NL-1) and phosphorus (0.6mg-PL-1) in SB were much lower than those of fed-batch conditions. The results suggested that SB could be a promising strategy to cultivate M. inermum NLP-F014 with the blended wastewater medium.


Subject(s)
Chlorophyta/growth & development , Microalgae/growth & development , Batch Cell Culture Techniques/economics , Biofuels/analysis , Bioreactors/economics , Cost-Benefit Analysis , Culture Media/chemistry , Nitrogen/chemistry , Phosphorus/chemistry , Wastewater/chemistry
16.
Phytomedicine ; 24: 134-140, 2017 Jan 15.
Article in English | MEDLINE | ID: mdl-28160853

ABSTRACT

BACKGROUND: Acetylshikonin is one of the biologically active compounds derived from the root of Lithospermum erythrorhizon, a medicinal plant with anti-cancer and anti-inflammation activity. Although there have been a few previous reports demonstrating that acetylshikonin exerts anti-cancer activity in vitro and in vivo, it is still not clear what is the exact molecular target protein of acetylshikonin in cancer cells. PURPOSE: The purpose of this study is to evaluate the inhibitory effect of acetylshikonin against CYP2J2 enzyme which is predominantly expressed in human tumor tissues and carcinoma cell lines. STUDY DESIGN: The inhibitory effect of acetylshikonin on the activities of CYP2J2-mediated metabolism were investigated using human liver microsomes (HLMs), and its cytotoxicity against human hepatoma HepG2 cells was also evaluated. METHOD: Astemizole, a representative CYP2J2 probe substrate, was incubated in HLMs in the presence or absence of acetylshikonin. After incubation, the samples were analyzed by liquid chromatography and triple quadrupole mass spectrometry. The anti-cancer activity of acetylshikonin was evaluated on human hepatocellular carcinoma HepG2 cells. WST-1, cell counting, and colony formation assays were further adopted for the estimation of the growth rate of HepG2 cells treated with acetylshikonin. RESULTS: Acetylshikonin inhibited CYP2J2-mediated astemizole O-demethylation activity (Ki = 2.1µM) in a noncompetitive manner. The noncompetitive inhibitory effect of acetylshikonin on CYP2J2 enzyme was also demonstrated using this 3D structure, which showed different binding location of astemizole and acetylshikonin in CYP2J2 model. It showed cytotoxic effects against human hepatoma HepG2 cells (IC50 = 2µM). In addition, acetylshikonin treatment inhibited growth of human hepatocellular carcinoma HepG2 cells leading to apoptosis accompanied with p53, bax, and caspase3 activation as well as bcl2 down-regulation. CONCLUSION: Taken together, our present study elucidates acetylshikonin displays the inhibitory effects against CYP2J2 in HLMs and anti-cancer activity in human hepatocellular carcinoma HepG2 cells.


Subject(s)
Anthraquinones/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Cytochrome P-450 Enzyme System/metabolism , Hep G2 Cells/drug effects , Liver Neoplasms/drug therapy , Microsomes, Liver/drug effects , Apoptosis/drug effects , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Humans , Phytotherapy , Plant Extracts/therapeutic use
17.
Am J Chin Med ; 44(4): 771-84, 2016.
Article in English | MEDLINE | ID: mdl-27222063

ABSTRACT

Beyond its role in the activation of protein C, the endothelial cell protein C receptor (EPCR) plays an important role in the cytoprotective pathway. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-[Formula: see text] converting enzyme (TACE). Pelargonidin is a well-known red pigment found in plants, and has been reported to have important biological activities that are potentially beneficial to human health. However, little is known about the effects of pelargonidin on EPCR shedding. We investigated this issue by monitoring the effects of pelargonidin on phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-[Formula: see text]-, interleukin (IL)-1ß-, and cecal ligation and puncture (CLP)-mediated EPCR shedding and by investigating the underlying mechanism of pelargonidin action. Data demonstrate that pelargonidin induced potent inhibition of PMA-, TNF-[Formula: see text]-, IL-1ß-, and CLP-induced EPCR shedding by inhibiting the phosphorylation of mitogen-activated protein kinases (MAPKs) such as p38, janus kinase (JNK), and extracellular signal-regulated kinase (ERK) 1/2. Pelargonidin also inhibited the expression and activity of PMA-induced TACE in endothelial cells. These results demonstrate the potential of pelargonidin as an anti-EPCR shedding reagent against PMA- and CLP-mediated EPCR shedding.


Subject(s)
ADAM17 Protein/metabolism , Anthocyanins/pharmacology , Antigens, CD/metabolism , Enzyme Inhibitors/pharmacology , Extracellular Signal-Regulated MAP Kinases/metabolism , Receptors, Cell Surface/metabolism , ADAM17 Protein/antagonists & inhibitors , ADAM17 Protein/genetics , Antigens, CD/genetics , Down-Regulation/drug effects , Endothelial Protein C Receptor , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Extracellular Signal-Regulated MAP Kinases/genetics , Humans , Interleukin-1beta/metabolism , Phosphorylation/drug effects , Receptors, Cell Surface/antagonists & inhibitors , Receptors, Cell Surface/genetics , Tetradecanoylphorbol Acetate/pharmacology , Tumor Necrosis Factor-alpha/metabolism
18.
Bioresour Technol ; 212: 182-189, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27099943

ABSTRACT

Selenium is said to be multifaceted element because it is essential at a low concentration but very toxic at an elevated level. For the purpose of screening a potential microorganism for selenite bioremediation, we isolated a bacterium, named strain THL1, which could perform both heterotrophic selenite reduction, using organic carbons such as acetate, lactate, propionate, and butyrate as electron donors under microaerobic condition, and electrotrophic selenite reduction, using an electrode polarized at -0.3V (vs. standard hydrogen electrode) as the sole electron donor under anaerobic condition. This bacterium determined to be a new strain of the genus Cronobacter, could remove selenite with an efficiency of up to 100%. This study is the first demonstration on a pure culture could take up electrons from an electrode to perform selenite reduction. The selenium nanoparticles produced by microbial selenite reduction might be considered for recovery and use in the nanotechnology industry.


Subject(s)
Carbon/metabolism , Cronobacter/metabolism , Electrodes , Selenious Acid/metabolism , Wastewater/microbiology , Biodegradation, Environmental , Carbon/chemistry , Cronobacter/isolation & purification , Electrons , Selenium/chemistry
19.
J Microbiol ; 52(8): 696-701, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25037880

ABSTRACT

The immune-modulatory as well as anti-influenza effects of Cordyceps extract were investigated using a DBA/2 mouse model. Three different concentrations of Cordyceps extract, red ginseng extract, or drinking water were orally administered to mice for seven days, and then the mice were intranasally infected with 2009 pandemic influenza H1N1 virus. Body weight changes and survival rate were measured daily post-infection. Plasma IL-12, TNF-α, and the frequency of natural killer (NK) cells were measured on day 4 post-infection. The DBA/2 strain was highly susceptible to H1N1 virus infection. We also found that Cordyceps extract had an anti-influenza effect that was associated with stable body weight and reduced mortality. The anti-viral effect of Cordyceps extract on influenza infection was mediated presumably by increased IL-12 expression and greater number of NK cells. However, high TNF-α expression after infection of H1N1 virus in mice not receiving treatment with Cordyceps extract suggested a two-sided effect of the extract on host immune regulation.


Subject(s)
Cordyceps/chemistry , Cordyceps/immunology , Immunomodulation , Influenza A Virus, H1N1 Subtype , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/therapy , Administration, Oral , Animals , Antiviral Agents/pharmacology , Dogs , Drinking Water , Humans , Interleukin-12/blood , Killer Cells, Natural/immunology , Madin Darby Canine Kidney Cells , Mice , Mice, Inbred DBA , Nasal Absorption , Panax , Plant Extracts/pharmacology , Tumor Necrosis Factor-alpha/blood
20.
Soc Cogn Affect Neurosci ; 9(12): 2067-77, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24532703

ABSTRACT

The arousal-biased competition model predicts that arousal increases the gain on neural competition between stimuli representations. Thus, the model predicts that arousal simultaneously enhances processing of salient stimuli and impairs processing of relatively less-salient stimuli. We tested this model with a simple dot-probe task. On each trial, participants were simultaneously exposed to one face image as a salient cue stimulus and one place image as a non-salient stimulus. A border around the face cue location further increased its bottom-up saliency. Before these visual stimuli were shown, one of two tones played: one that predicted a shock (increasing arousal) or one that did not. An arousal-by-saliency interaction in category-specific brain regions (fusiform face area for salient faces and parahippocampal place area for non-salient places) indicated that brain activation associated with processing the salient stimulus was enhanced under arousal whereas activation associated with processing the non-salient stimulus was suppressed under arousal. This is the first functional magnetic resonance imaging study to demonstrate that arousal can enhance information processing for prioritized stimuli while simultaneously impairing processing of non-prioritized stimuli. Thus, it goes beyond previous research to show that arousal does not uniformly enhance perceptual processing, but instead does so selectively in ways that optimizes attention to highly salient stimuli.


Subject(s)
Arousal/physiology , Bias , Brain/physiology , Competitive Behavior/physiology , Fear/physiology , Acoustic Stimulation , Adolescent , Adult , Brain/blood supply , Conditioning, Classical , Female , Galvanic Skin Response/physiology , Humans , Image Processing, Computer-Assisted , Linear Models , Magnetic Resonance Imaging , Male , Oxygen/blood , Photic Stimulation , Reaction Time , Young Adult
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