Publications by authors named "Yi-Chung Liu"

14 Publications

  • Page 1 of 1

Imperatorin Interferes with LPS Binding to the TLR4 Co-Receptor and Activates the Nrf2 Antioxidative Pathway in RAW264.7 Murine Macrophage Cells.

Antioxidants (Basel) 2021 Feb 27;10(3). Epub 2021 Feb 27.

Department of Pharmacology, China Medical University, Taichung 404333, Taiwan.

Imperatorin (IMP) could downregulate several inflammatory transcription factor signaling pathways. Some studies have pointed out that IMP could interfere with toll-like receptor 4 (TLR4) signaling. This study evaluates how IMP interferes with the TLR4 co-receptors signaling through the protein-ligand docking model, Western blotting, immunofluorescence (IF), and atomic force microscopy (AFM) assays in lipopolysaccharide (LPS) stimulated macrophage-like RAW264.7 cells in vitro. The results of the protein-ligand docking demonstrate that IMP interferes with LPS binding to the LPS-binding protein (LBP), the cluster of differentiation 14 (CD14), and the toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD-2) co-receptors in LPS-stimulated RAW264.7 cells. Compared with TLR4 antagonist CLI-095 or dexamethasone, IMP could suppress the protein expressions of LBP, CD14, and TLR4/MD-2 in LPS-stimulated cells. Furthermore, the three-dimensional (3D) image assay of the AFM showed IMP could prevent the LPS-induced morphological change in RAW264.7 cells. Additionally, IMP could activate the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, and it increased the antioxidative protein expression of heme oxygenase-1 (HO-1), superoxidase dismutase (SOD), and catalase (CAT). Our results are the first to reveal that the anti-inflammatory effect of IMP interferes with LPS binding to TLR4 co-receptor signaling and activates the antioxidative Nrf2 signaling pathway.
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http://dx.doi.org/10.3390/antiox10030362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997471PMC
February 2021

Cafestol Inhibits High-Glucose-Induced Cardiac Fibrosis in Cardiac Fibroblasts and Type 1-Like Diabetic Rats.

Evid Based Complement Alternat Med 2020 31;2020:4503747. Epub 2020 Dec 31.

School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.

Diabetes is associated with the development of myocardial fibrosis, which is related to various cardiac diseases. Cafestol, one of the active ingredients in coffee, has been reported to exert biological effects. However, whether cafestol can ameliorate diabetes-induced cardiac fibrosis remains unknown. The aim of this study was to evaluate the effects of cafestol on cardiac fibrosis in high-glucose-treated cardiac fibroblasts and streptozocin- (STZ-) induced diabetic rats. Rat cardiac fibroblasts were cultured in high-glucose (25 mM) media in the absence or presence of cafestol, and the changes in collagen synthesis, transforming growth factor-1 (TGF-1) production, and related signaling molecules were assessed on the basis of H-proline incorporation, enzyme-linked immunosorbent assay, and western blotting. Cardiac fibroblasts exposed to high-glucose conditions exhibited increased collagen synthesis, TGF-1 production, and Smad2/3 phosphorylation, and these effects were mitigated by cafestol treatment. Furthermore, cafestol increased the translocation of nuclear factor erythroid 2-related factor 2 and increased the expression of heme oxygenase-1. The results of molecular docking analysis suggested a selective interaction of cafestol with Kelch-like ECH-associated protein 1. The rats with untreated STZ-induced diabetes exhibited considerable collagen accumulation, which was ameliorated by cafestol. Moreover, activities of catalase, superoxide dismutase, general matrix metalloproteinase, and reduced glutathione concentration were upregulated, whereas malondialdehyde level was downregulated by treatment with cafestol in rats with cardiac fibrosis. These findings highlight the effects of cafestol, which may be useful in treating diabetes-related cardiac fibrosis.
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http://dx.doi.org/10.1155/2020/4503747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790572PMC
December 2020

An essential role of acetyl coenzyme A in the catalytic cycle of insect arylalkylamine N-acetyltransferase.

Commun Biol 2020 08 14;3(1):441. Epub 2020 Aug 14.

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 30013, Taiwan.

Acetyl coenzyme A (Ac-CoA)-dependent N-acetylation is performed by arylalkylamine N-acetyltransferase (AANAT) and is important in many biofunctions. AANAT catalyzes N-acetylation through an ordered sequential mechanism in which cofactor (Ac-CoA) binds first, with substrate binding afterward. No ternary structure containing AANAT, cofactor, and substrate was determined, meaning the details of substrate binding and product release remain unclear. Here, two ternary complexes of dopamine N-acetyltransferase (Dat) before and after N-acetylation were solved at 1.28 Å and 1.36 Å resolution, respectively. Combined with the structures of Dat in apo form and Ac-CoA bound form, we addressed each stage in the catalytic cycle. Isothermal titration calorimetry (ITC), crystallography, and nuclear magnetic resonance spectroscopy (NMR) were utilized to analyze the product release. Our data revealed that Ac-CoA regulates the conformational properties of Dat to form the catalytic site and substrate binding pocket, while the release of products is facilitated by the binding of new Ac-CoA.
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http://dx.doi.org/10.1038/s42003-020-01177-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427786PMC
August 2020

Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2.

Mar Drugs 2020 Aug 9;18(8). Epub 2020 Aug 9.

Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd., Jiaushi, Ilan 262, Taiwan.

Tilapia piscidin (TP) 4 is an antimicrobial peptide derived from Nile tilapia (), which shows broad-spectrum antibacterial activity and excellent cancer-killing ability in vitro and in vivo. Like many other antimicrobial peptides, TP4 treatment causes mitochondrial toxicity in cancer cells. However, the molecular mechanisms underlying TP4 targeting of mitochondria remain unclear. In this study, we used a pull-down assay on A549 cell lysates combined with LC-MS/MS to discover that TP4 targets adenine nucleotide translocator (ANT) 2, a protein essential for adenine nucleotide exchange across the inner membrane. We further showed that TP4 accumulates in mitochondria and colocalizes with ANT2. Moreover, molecular docking studies showed that the interaction requires Phe1, Ile2, His3, His4, Ser11, Lys14, His17, Arg21, Arg24 and Arg25 residues in TP4 and key residues within the cavity of ANT2. These findings suggest a mechanism by which TP4 may induce mitochondrial dysfunction to disrupt cellular energy metabolism.
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http://dx.doi.org/10.3390/md18080417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459631PMC
August 2020

MAP4K3/GLK Promotes Lung Cancer Metastasis by Phosphorylating and Activating IQGAP1.

Cancer Res 2019 10 20;79(19):4978-4993. Epub 2019 Aug 20.

Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan.

Overexpression of the serine/threonine kinase GLK/MAP4K3 in human lung cancer is associated with poor prognosis and recurrence, however, the role of GLK in cancer recurrence remains unclear. Here, we report that transgenic GLK promotes tumor metastasis and cell migration through the scaffold protein IQ motif-containing GTPase-activating protein 1(IQGAP1). GLK transgenic mice displayed enhanced distant metastasis. IQGAP1 was identified as a GLK-interacting protein; two proline-rich regions of GLK and the WW domain of IQGAP1 mediated this interaction. GLK and IQGAP1 colocalized at the leading edge including filopodia and lamellipodia of migrating cells. GLK directly phosphorylated IQGAP1 at Ser-480 enhancing Cdc42 activation and subsequent cell migration. GLK-induced cell migration and lung cancer metastasis were abolished by IQGAP1 depletion. Consistently, human NSCLC patient tissues displayed increased phospho-IQGAP1, which correlated with poor survival. Collectively, GLK promotes lung cancer metastasis by binding to, phosphorylating, and activating IQGAP1. SIGNIFICANCE: These findings show the critical role of the GLK-IQGAP cascade in cell migration and tumor metastasis, suggesting it as a potential biomarker and therapeutic target for lung cancer recurrence.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-1402DOI Listing
October 2019

Nile Tilapia Derived Antimicrobial Peptide TP4 Exerts Antineoplastic Activity Through Microtubule Disruption.

Mar Drugs 2018 Nov 22;16(12). Epub 2018 Nov 22.

Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, Ilan 262, Taiwan.

Some antimicrobial peptides (AMPs) exhibit anti-cancer activity, acting on cancer cells either by causing membrane lysis or via intracellular effects. While intracellular penetration of AMPs has been shown to cause cancer cell death, the mechanisms of toxicity remain largely unknown. Here we show that a tilapia-derived AMP, Tilapia piscidin (TP) 4, penetrates intracellularly and targets the microtubule network. A pull-down assay identified α-Tubulin as a major interaction partner for TP4, and molecular docking analysis suggested that Phe1, Ile16, and Arg23 on TP4 are required for the interaction. TP4 treatment in A549 cells was found to disrupt the microtubule network in cells, and mutation of the essential TP4 residues prevented microtubule depolymerization in vitro. Importantly, the TP4 mutants also showed decreased cytotoxicity in A549 cells, suggesting that microtubule disruption is a major mechanistic component of TP4-mediated death in lung carcinoma cells.
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http://dx.doi.org/10.3390/md16120462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315541PMC
November 2018

Role of the RAD51-SWI5-SFR1 Ensemble in homologous recombination.

Nucleic Acids Res 2016 07 30;44(13):6242-51. Epub 2016 Apr 30.

Institute of Biochemical Sciences, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan

During DNA double-strand break and replication fork repair by homologous recombination, the RAD51 recombinase catalyzes the DNA strand exchange reaction via a helical polymer assembled on single-stranded DNA, termed the presynaptic filament. Our published work has demonstrated a dual function of the SWI5-SFR1 complex in RAD51-mediated DNA strand exchange, namely, by stabilizing the presynaptic filament and maintaining the catalytically active ATP-bound state of the filament via enhancement of ADP release. In this study, we have strived to determine the basis for physical and functional interactions between Mus musculus SWI5-SFR1 and RAD51. We found that SWI5-SFR1 preferentially associates with the oligomeric form of RAD51. Specifically, a C-terminal domain within SWI5 contributes to RAD51 interaction. With specific RAD51 interaction defective mutants of SWI5-SFR1 that we have isolated, we show that the physical interaction is indispensable for the stimulation of the recombinase activity of RAD51. Our results thus help establish the functional relevance of the trimeric RAD51-SWI5-SFR1 complex and provide insights into the mechanistic underpinnings of homology-directed DNA repair in mammalian cells.
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http://dx.doi.org/10.1093/nar/gkw375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291256PMC
July 2016

MMP-13 is involved in oral cancer cell metastasis.

Oncotarget 2016 03;7(13):17144-61

Department of Medical Sciences and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.

The oral cancer cell line OC3-I5 with a highly invasive ability was selected and derived from an established OSCC line OC3. In this study, we demonstrated that matrix metalloproteinases protein MMP-13 was up-regulated in OC3-I5 than in OC3 cells. We also observed that expression of epithelial-mesenchymal transition (EMT) markers including Twist, p-Src, Snail1, SIP1, JAM-A, and vinculin were increased in OC3-I5 compared to OC3 cells, whereas E-cadherin expression was decreased in the OC3-I5 cells. Using siMMP-13 knockdown techniques, we showed that siMMP-13 not only reduced the invasion and migration, but also the adhesion abilities of oral cancer cells. In support of the role of MMP-13 in metastasis, we used MMP-13 expressing plasmid-transfected 293T cells to enhance MMP-13 expression in the OC3 cells, transplanting the MMP-13 over expressing OC3 cells into nude mice led to enhanced lung metastasis. In summary, our findings show that MMP-13 promotes invasion and metastasis in oral cancer cells, suggesting altered expression of MMP-13 may be utilized to impede the process of metastasis.
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http://dx.doi.org/10.18632/oncotarget.7942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941377PMC
March 2016

Complete Genome Sequence of Xanthomonas campestris pv. campestris Strain 17 from Taiwan.

Genome Announc 2015 Dec 17;3(6). Epub 2015 Dec 17.

Institute of Biochemistry and NCHU Biotechnological Center, National Chung Hsing University, Taichung, Taiwan

Xanthomonas campestris pv. campestris 17 is a Gram-negative bacterium that is phytopathogenic to cruciferous plants in Taiwan. The 4,994,426-bp-long genome consists of 24 contigs with 4,050 protein-coding genes, 1 noncoding RNA (ncRNA) gene, 6 rRNA genes, and 55 tRNA genes.
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http://dx.doi.org/10.1128/genomeA.01466-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683227PMC
December 2015

Analysis of differentially expressed novel post-translational modifications of plasma apolipoprotein E in Taiwanese females with breast cancer.

J Proteomics 2015 Aug 12;126:252-62. Epub 2015 Jun 12.

School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; PhD, Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan. Electronic address:

APOE ε2 or ε4 alleles being used as indicators of breast cancer risk are controversial in Taiwanese females. We provide a concept for relative comparisons of post-translational modifications (PTMs) of plasma apolipoprotein E (ApoE) between normal controls and breast cancer patients to investigate the association of ApoE with breast cancer risk. APOE polymorphisms (ApoE isoforms) were not assessed in this study. The relative modification ratio (%) of 15 targeted and 21 modified peptides were evaluated by 1D SDS-PAGE, in-gel digestion, and label-free nano-LC/MS to compare normal controls with breast cancer patients. Plasma levels of the ApoE protein did not significantly differ between normal controls and breast cancer patients. Eleven sites with novel PTMs were identified from 7 pairs of differentially expressed targeted and modified peptides according to the relative modification ratio including methylation at the E3 (↑1.45-fold), E7 (↑1.45-fold), E11 (↑1.19-fold), E77 (↑2.02-fold), E87 (↑2.02-fold), and Q98 (↑1.62-fold) residues; dimethylation at the Q187 (↑1.44-fold) residue; dihydroxylation at the R92 (↑1.25-fold), K95 (↑1.25-fold), and R103 (↑1.25-fold) residues; and glycosylation at the S129 (↑1.14-fold) residue. The clustered methylation and dihydroxylation of plasma ApoE proteins may play a role in breast cancer.
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http://dx.doi.org/10.1016/j.jprot.2015.05.038DOI Listing
August 2015

Relations among depression, self-efficacy and optimism in a sample of nurses in Taiwan.

J Nurs Manag 2011 Sep 19;19(6):769-76. Epub 2011 Apr 19.

College of Management, Yuan Ze University, Chungli, Taiwan.

Aims: The present study investigated the level of depression among hospital nurses, to examine personality contributions to depression and to offer managers relevant organizational strategies to reduce levels of depression.

Background: The World Health Organization's Global Burden of Disease Study estimates that major depression is the leading cause of disability among women in the world today. It is surprising that there is a relative dearth of research investigating depression among nursing staff.

Method: A cross-sectional survey of 314 staff nurses in a general hospital in Taiwan. Participants completed a set of questionnaires and a demographic information form. A number of statistical methods were used including descriptive statistics, product-moment correlations and multiple regression analysis.

Results: In all, 52.5% of nurses reported mild-to-moderate depressive symptoms. Self-efficacy and optimism were significant buffers against depression.

Conclusions: The results of the present study confirm the importance of self-efficacy and optimism. Nurses with positive evaluation and expectation towards their self and others tend to report lower depression levels.

Implications For Nursing Management: The results of the present study indicate that there is an immediate need to pay further attention to nurses' depression issues. It is therefore suggested that Nursing Managers take an empowering approach to strengthen nurses' self-efficacy and optimism levels to prevent depression in this profession.
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http://dx.doi.org/10.1111/j.1365-2834.2010.01180.xDOI Listing
September 2011

DSAP: deep-sequencing small RNA analysis pipeline.

Nucleic Acids Res 2010 Jul 16;38(Web Server issue):W385-91. Epub 2010 May 16.

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.

DSAP is an automated multiple-task web service designed to provide a total solution to analyzing deep-sequencing small RNA datasets generated by next-generation sequencing technology. DSAP uses a tab-delimited file as an input format, which holds the unique sequence reads (tags) and their corresponding number of copies generated by the Solexa sequencing platform. The input data will go through four analysis steps in DSAP: (i) cleanup: removal of adaptors and poly-A/T/C/G/N nucleotides; (ii) clustering: grouping of cleaned sequence tags into unique sequence clusters; (iii) non-coding RNA (ncRNA) matching: sequence homology mapping against a transcribed sequence library from the ncRNA database Rfam (http://rfam.sanger.ac.uk/); and (iv) known miRNA matching: detection of known miRNAs in miRBase (http://www.mirbase.org/) based on sequence homology. The expression levels corresponding to matched ncRNAs and miRNAs are summarized in multi-color clickable bar charts linked to external databases. DSAP is also capable of displaying miRNA expression levels from different jobs using a log(2)-scaled color matrix. Furthermore, a cross-species comparative function is also provided to show the distribution of identified miRNAs in different species as deposited in miRBase. DSAP is available at http://dsap.cgu.edu.tw.
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http://dx.doi.org/10.1093/nar/gkq392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896168PMC
July 2010

Botulinum toxin type a in the prophylactic treatment of transformed migraine in Taiwanese patients: a review of 30 consecutive cases.

J Chin Med Assoc 2007 Dec;70(12):535-40

Department of Neurology, Ten Chan [corrected] Hospital, Chung-Li, Taiwan, R O C.

Background: Botulinum toxin type A (BoNT-A) for the treatment of patients with various forms of migraine has been studied, but there is a paucity of data regarding the use of BoNT-A in Asian headache patients. Our study was designed to evaluate the efficacy of BoNT-A in the treatment of transformed migraine (TM) in a population of Taiwanese patients.

Methods: We retrospectively analyzed 30 patients who underwent BoNT-A treatment for TM from July 2003 to May 2004. Of 30 patients, 14 had palpable muscle tenderness (or tender points) in the pericranial region and 16 did not. All patients received injections into the corrugator, procerus, frontalis, and temporalis muscles (a total of 30 U), while a subset of TM patients with tender points (6 of 14 patients) also received injections to additional muscles based on a follow-the-tenderness approach (mean dose, 45 U).

Results: Twenty-seven of the 30 patients (90%) surveyed reported effective relief of their symptoms with BoNT-A treatment (at least a 50% reduction in the number of headache days or in headache intensity). The greatest reduction in headache days per month and headache intensity was found in TM patients with tender points who received a mean dose of 45 U compared to those who received fixed-site dosing of 30 U.

Conclusion: Our results suggest that BoNT-A may be an effective prophylactic treatment for TM in Taiwanese patients. Interestingly, similar efficacy was demonstrated in TM patients with tender points compared to those without tender points when an additional dose of BoNT-A was injected into the tender muscles in the former.
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http://dx.doi.org/10.1016/S1726-4901(08)70056-XDOI Listing
December 2007