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Article ; Online: Feedback Regulation of O -GlcNAc Transferase through Translation Control to Maintain Intracellular O -GlcNAc Homeostasis

Chia-Hung Lin / Chen-Chung Liao / Mei-Yu Chen / Teh-Ying Chou

International Journal of Molecular Sciences, Vol 22, Iss 3463, p

2021 Volume 3463

Abstract: Protein O -GlcNAcylation is a dynamic post-translational modification involving the attachment of N -acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O -GlcNAc ... ...

Abstract	Protein O -GlcNAcylation is a dynamic post-translational modification involving the attachment of N -acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O -GlcNAc cycling on substrate proteins: O -GlcNAc transferase (OGT) catalyzes the addition while O -GlcNAcase (OGA) helps the removal of GlcNAc. O -GlcNAcylation modifies protein functions; therefore, dysregulation of O -GlcNAcylation affects cell physiology and contributes to pathogenesis. To maintain homeostasis of cellular O -GlcNAcylation, there exists feedback regulation of OGT and OGA expression responding to fluctuations of O -GlcNAc levels; yet, little is known about the molecular mechanisms involved. In this study, we investigated the O -GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells. Results suggest that, upon alterations in O -GlcNAcylation, the regulation of OGA expression occurs at the mRNA level and likely involves epigenetic mechanisms, while modulation of OGT expression is through translation control. Further analyses revealed that the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) contributes to the downregulation of OGT induced by hyper- O -GlcNAcylation; the S5A/S6A O -GlcNAcylation-site mutant of 4E-BP1 cannot support this regulation, suggesting an important role of O -GlcNAcylation. The results provide additional insight into the molecular mechanisms through which cells may fine-tune intracellular O -GlcNAc levels to maintain homeostasis.
Keywords	epigenetics ; eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) ; histone deacetylase (HDAC) ; O -GlcNAcase (OGA) ; O -GlcNAcylation ; O -linked N -acetylglucosamine ( O -GlcNAc) ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The influence of temperature on inter-yarns fictional properties of shear thickening fluids treated Kevlar fabrics

Wang, Qiu-shi / Run-jun Sun / Mu Yao / Mei-yu Chen / Yan Feng

Composites. 2019 Jan., v. 116

2019

Abstract: Shear thickening fluids (STFs) treated Kevlar fabrics have been widely used to fabricate the flexible body armors and the STFs can be subjected to a variable temperature in many service environments. Therefore, the rheological properties of the STFs ... ...

Abstract	Shear thickening fluids (STFs) treated Kevlar fabrics have been widely used to fabricate the flexible body armors and the STFs can be subjected to a variable temperature in many service environments. Therefore, the rheological properties of the STFs prepared by dispersing monodisperse polystyrene (PS) microspheres in polyethylene glycol 200 (PEG200) were investigated at the temperature from −15 °C to 35 °C and the inter-yarns frictional properties of neat and STFs-treated Kevlar fabrics were investigated for six different pull-out speeds at −15 °C and 25 °C to evaluate the contribution of the STFs treatments. The STFs effectively improved the inter-yarns friction and the trigger of shear thickening in STFs-treated fabrics was achieved in some specific speed which was about 50 mm/min for PS/PEG200-based STFs-treated Kevlar fabrics at −15 °C. The improvement of friction caused by the microspheres among the yarns and filaments was demonstrated to be the main reason for the enhancement of the STFs-treated fabrics.
Keywords	composite materials ; fabrics ; friction ; microparticles ; polyethylene glycol ; polystyrenes ; rheological properties ; temperature ; yarns
Language	English
Dates of publication	2019-01
Size	p. 46-53.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2012223-8
ISSN	1359-835X
ISSN	1359-835X
DOI	10.1016/j.compositesa.2018.10.020
Database	NAL-Catalogue (AGRICOLA)

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Article: [Sorption Behaviors of Copper Ions and Tetracycline on Microplastics in Aqueous Solution].

Xue, Xiang-Dong / Wang, Xing-Yuan / Mei, Yu-Chen / Zhuang, Hai-Feng / Song, Ya-Li / Fang, Cheng-Ran

Huan jing ke xue= Huanjing kexue

2020 Volume 41, Issue 8, Page(s) 3675–3683

Abstract: The interaction between microplastics, heavy metals, and antibiotics can lead to combined pollution, which could result in greater environmental damage. The pathway and mechanism of the interaction between microplastics, heavy metals, and antibiotics are ...

Abstract	The interaction between microplastics, heavy metals, and antibiotics can lead to combined pollution, which could result in greater environmental damage. The pathway and mechanism of the interaction between microplastics, heavy metals, and antibiotics are the preconditions for evaluating the associated environmental risk; however, these are not well understood. As probe sorbates, the sorption behaviors of copper ions (Cu
MeSH term(s)	Adsorption ; Anti-Bacterial Agents ; Copper/analysis ; Hydrogen-Ion Concentration ; Ions ; Kinetics ; Microplastics ; Plastics ; Water Pollutants, Chemical/analysis
Chemical Substances	Anti-Bacterial Agents ; Ions ; Microplastics ; Plastics ; Water Pollutants, Chemical ; Copper (789U1901C5)
Language	Chinese
Publishing date	2020-10-29
Publishing country	China
Document type	Journal Article
ISSN	0250-3301
ISSN	0250-3301
DOI	10.13227/j.hjkx.202002196
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Recombinant lipidated Zika virus envelope protein domain III elicits durable neutralizing antibody responses against Zika virus in mice

Mei-Yu Chen / Kit Man Chai / Chen-Yi Chiang / Chiao-Chieh Wu / Guann-Yi Yu / Shih-Jen Liu / Hsin-Wei Chen

Journal of Biomedical Science, Vol 27, Iss 1, Pp 1-

2020 Volume 11

Abstract: Abstract Background The emergence of Zika virus (ZV) in tropical and subtropical areas of the world has created an urgent need for vaccines against ZV. However, approved vaccines that prevent ZV infection are not available. To develop an effective ... ...

Abstract	Abstract Background The emergence of Zika virus (ZV) in tropical and subtropical areas of the world has created an urgent need for vaccines against ZV. However, approved vaccines that prevent ZV infection are not available. To develop an effective vaccine against ZV infection, a lipidated form of ZV envelope protein domain III that possesses an intrinsic adjuvant property was rationally designed. Our goal was to examine the immunogenicity of recombinant lipidated ZV envelope protein domain III (rLZE3) and evaluate its potential as a vaccine candidate against ZV. Methods Recombinant ZV envelope protein domain III (rZE3) and rLZE3 were prepared with an Escherichia coli-based system. Dendritic cell surface marker expression and cytokine production upon stimulation were analyzed to evaluate the function of rLZE3. Neutralizing antibody capacities were evaluated using focus reduction neutralization tests after immunization. To investigate the protective immunity in immunized mice, serum samples collected from immunized mice were adoptively transferred into AG129 mice, and then viremia levels and survival times were examined after ZV challenge. Results rLZE3 alone but not rZE3 alone efficiently activated dendritic cells in vitro and was taken up by dendritic cells in vivo. Immunization of C57BL/6 mice with rLZE3 alone (without exogenous adjuvant) could induce ZV-specific neutralizing antibody responses. Furthermore, serum samples obtained from rLZE3-immunized mice provided protection as indicated by a reduction in viremia levels and prolongation of survival times after ZV challenge. Conclusion These results indicate that rLZE3 is an excellent vaccine candidate and has great potential that should be evaluated in further preclinical studies.
Keywords	Envelope protein domain III ; Neutralizing antibody ; Recombinant lipoprotein ; Vaccine ; Zika virus ; Medicine ; R
Subject code	570
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: DNA vaccination induced protective immunity against SARS CoV-2 infection in hamsterss.

Kit Man Chai / Tsai-Teng Tzeng / Kuan-Yin Shen / Hung-Chun Liao / Jhe-Jhih Lin / Mei-Yu Chen / Guann-Yi Yu / Horng-Yunn Dou / Ching-Len Liao / Hsin-Wei Chen / Shih-Jen Liu

PLoS Neglected Tropical Diseases, Vol 15, Iss 5, p e

2021 Volume 0009374

Abstract: The development of efficient vaccines against COVID-19 is an emergent need for global public health. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major target for the COVID-19 vaccine. To quickly respond to the ... ...

Abstract	The development of efficient vaccines against COVID-19 is an emergent need for global public health. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major target for the COVID-19 vaccine. To quickly respond to the outbreak of the SARS-CoV-2 pandemic, a nucleic acid-based vaccine is a novel option, beyond the traditional inactivated virus vaccine or recombinant protein vaccine. Here, we report a DNA vaccine containing the spike gene for delivery via electroporation. The spike genes of SARS-CoV and SARS-CoV-2 were codon optimized for mammalian cell expression and then cloned into mammalian cell expression vectors, called pSARS-S and pSARS2-S, respectively. Spike protein expression was confirmed by immunoblotting after transient expression in HEK293T cells. After immunization, sera were collected for antigen-specific antibody and neutralizing antibody titer analyses. We found that both pSARS-S and pSARS2-S immunization induced similar levels of antibodies against S2 of SARS-CoV-2. In contrast, only pSARS2-S immunization induced antibodies against the receptor-binding domain of SARS-CoV-2. We further found that pSARS2-S immunization, but not pSARS-S immunization, could induce very high titers of neutralizing antibodies against SARS-CoV-2. We further analyzed SARS-CoV-2 S protein-specific T cell responses and found that the immune responses were biased toward Th1. Importantly, pSARS2-S immunization in hamsters could induce protective immunity against SARS-CoV-2 challenge in vivo. These data suggest that DNA vaccination could be a promising approach for protecting against COVID-19.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human Costars Family Protein ABRACL Modulates Actin Dynamics and Cell Migration and Associates with Tumorigenic Growth

Bo-Yuan Hsiao / Chia-Hsin Chen / Ho-Yi Chi / Pei-Ru Yen / Ying-Zhen Yu / Chia-Hsin Lin / Te-Ling Pang / Wei-Chi Lin / Min-Lun Li / Yi-Chen Yeh / Teh-Ying Chou / Mei-Yu Chen

International Journal of Molecular Sciences, Vol 22, Iss 4, p

2021 Volume 2037

Abstract: Regulation of cellular actin dynamics is pivotal in driving cell motility. During cancer development, cells migrate to invade and spread; therefore, dysregulation of actin regulators is often associated with cancer progression. Here we report the role of ...

Abstract	Regulation of cellular actin dynamics is pivotal in driving cell motility. During cancer development, cells migrate to invade and spread; therefore, dysregulation of actin regulators is often associated with cancer progression. Here we report the role of ABRACL, a human homolog of the Dictyostelium actin regulator Costars, in migration and tumorigenic growth of cancer cells. We found a correlation between ABRACL expression and the migratory ability of cancer cells. Cell staining revealed the colocalization of ABRACL and F-actin signals at the leading edge of migrating cells. Analysis of the relative F-/G-actin contents in cells lacking or overexpressing ABRACL suggested that ABRACL promotes cellular actin distribution to the polymerized fraction. Physical interaction between ABRACL and cofilin was supported by immunofluorescence staining and proximity ligation. Additionally, ABRACL hindered cofilin-simulated pyrene F-actin fluorescence decay in vitro, indicating a functional interplay. Lastly, analysis on a colorectal cancer cohort demonstrated that high ABRACL expression was associated with distant metastasis, and further exploration showed that depletion of ABRACL expression in colon cancer cells resulted in reduced cell proliferation and tumorigenic growth. Together, results suggest that ABRACL modulates actin dynamics through its interaction with cofilin and thereby regulates cancer cell migration and participates in cancer pathogenesis.
Keywords	actin regulator ; cell migration ; cofilin ; colorectal cancer ; tumorigenesis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy

Chen-Yi Chiang / Mei-Yu Chen / Chia-Wei Hsu / Chia-Yeh Liu / Yu-Wen Tsai / Hung-Chun Liao / Jia-Ying Yan / Zih-Shiuan Chuang / Hsin-I. Wang / Chien-Hsiung Pan / Chia-Yi Yu / Guann-Yi Yu / Ching-Len Liao / Shih-Jen Liu / Hsin-Wei Chen

Journal of Biomedical Science, Vol 29, Iss 1, Pp 1-

2022 Volume 13

Abstract: Abstract Background Calls for the coronavirus to be treated as an endemic illness, such as the flu, are increasing. After achieving high coverage of COVID-19 vaccination, therapeutic drugs have become important for future SARS-CoV-2 variant outbreaks. ... ...

Abstract	Abstract Background Calls for the coronavirus to be treated as an endemic illness, such as the flu, are increasing. After achieving high coverage of COVID-19 vaccination, therapeutic drugs have become important for future SARS-CoV-2 variant outbreaks. Although many monoclonal antibodies have been approved for emergency use as treatments for SARS-CoV-2 infection, some monoclonal antibodies are not authorized for variant treatment. Broad-spectrum monoclonal antibodies are unmet medical needs. Methods We used a DNA prime-protein boost approach to generate high-quality monoclonal antibodies. A standard ELISA was employed for the primary screen, and spike protein-human angiotensin-converting enzyme 2 blocking assays were used for the secondary screen. The top 5 blocking clones were selected for further characterization, including binding ability, neutralization potency, and epitope mapping. The therapeutic effects of the best monoclonal antibody against SARS-CoV-2 infection were evaluated in a hamster infection model. Results Several monoclonal antibodies were selected that neutralize different SARS-CoV-2 variants of concern (VOCs). These VOCs include Alpha, Beta, Gamma, Delta, Kappa and Lambda variants. The high neutralizing antibody titers against the Beta variant would be important to treat Beta-like variants. Among these monoclonal antibodies, mAb-S5 displays the best potency in terms of binding affinity and neutralizing capacity. Importantly, mAb-S5 protects animals from SARS-CoV-2 challenge, including the Wuhan strain, D614G, Alpha and Delta variants, although mAb-S5 exhibits decreased neutralization potency against the Delta variant. Furthermore, the identified neutralizing epitopes of monoclonal antibodies are all located in the receptor-binding domain (RBD) of the spike protein but in different regions. Conclusions Our approach generates high-potency monoclonal antibodies against a broad spectrum of VOCs. Multiple monoclonal antibody combinations may be the best strategy to treat future SARS-CoV-2 variant ...
Keywords	COVID-19 ; Monoclonal antibody ; Neutralization ; SARS-CoV-2 ; Variant ; Medicine ; R
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Detection and quantification of dengue virus using a novel biosensor system based on dengue NS3 protease activity.

Ming-Shu Hsieh / Mei-Yu Chen / Chun-Hsiang Hsieh / Chien-Hsiung Pan / Guann-Yi Yu / Hsin-Wei Chen

PLoS ONE, Vol 12, Iss 11, p e

2017 Volume 0188170

Abstract: The traditional methods, plaque assays and immuno-focus assays, used to titrate infectious dengue virus (DENV) particles are time consuming and labor intensive. Here, we developed a DENV protease activity detection system (DENPADS) to visualize DENV ... ...

Abstract	The traditional methods, plaque assays and immuno-focus assays, used to titrate infectious dengue virus (DENV) particles are time consuming and labor intensive. Here, we developed a DENV protease activity detection system (DENPADS) to visualize DENV infection in cells based on dengue protease activity.Dengue NS3 protease cleaves NS4B-NS5. BHK-21 cells stably expressing the sensor module comprising DENV-2 NS4 and the 10 amino-terminal amino acids of NS5 (N10NS5) fused with the SV40 nuclear localization signal (NLS) and Cre recombinase (Cre), were generated. Cre is constrained outside the nucleus in the absence of NS3 activity but translocates into the nucleus through NS4B-NS5 cleavage when cells are infected with DENV. Nuclear translocation of Cre can trigger the reporter system, which contains a cis-loxP-flanked mCherry with three continuous stop codons following an SV40 polyA tail cDNA upstream of EGFP or mHRP cDNA. Our results show that DENPADS is an efficient and accurate method to titrate 4 DENV serotypes in 24 hours. Compared with current virus titration methods, the entire process is easy to perform, and the data are easily acquired.In this study, we demonstrate that DENPADS can be used to detect dengue viral infection through a fluorescence switch or HRP activity in the infected cells. This approach is sensitive with less incubation time and labor input. In addition, DENPADS can simultaneously evaluate the efficacy and cytotoxicity of potential anti-DENV candidates. Overall, DENPADS is a useful tool for dengue research.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Recombinant lipidated dengue-4 envelope protein domain III elicits protective immunity

Chiang, Chen-Yi / Chih-Hsiang Leng / Chun-Hsiang Hsieh / Hsin-Wei Chen / Hsueh-Hung Liu / Jy-Ping Tsai / Mei-Yu Chen / Pele Chong / Shih-Jen Liu

Vaccine. 2014 Mar. 10, v. 32, no. 12

2014

Abstract: The combination of recombinant protein antigens with an immunostimulator has the potential to greatly increase the immunogenicity of recombinant protein antigens. In the present study, we selected the dengue-4 envelope protein domain III as a dengue ... ...

Abstract	The combination of recombinant protein antigens with an immunostimulator has the potential to greatly increase the immunogenicity of recombinant protein antigens. In the present study, we selected the dengue-4 envelope protein domain III as a dengue vaccine candidate and expressed the protein in lipidated form using an Escherichia coli-based system. The recombinant lipidated dengue-4 envelope protein domain III folded into the proper conformation and competed with the dengue-4 virus for cellular binding sites. Mice immunized with lipidated dengue-4 envelope protein domain III without exogenous adjuvant had higher frequencies of dengue-4 envelope protein domain III-specific B cells secreting antibodies than mice immunized with the nonlipidated form. Importantly, lipidated dengue-4 envelope protein domain III-immunized mice demonstrated a durable neutralizing antibody response and had reduced viremia levels after challenge. The study demonstrates that lipidated dengue-4 envelope protein domain III is immunogenic and may be a potential dengue vaccine candidate. Furthermore, the lipidation strategy can be applied to other serotypes of dengue virus.
Keywords	adjuvants ; antigens ; binding sites ; dengue ; Dengue virus ; immune response ; mice ; neutralizing antibodies ; recombinant proteins ; serotypes ; vaccines ; viremia ; viruses
Language	English
Dates of publication	2014-0310
Size	p. 1346-1353.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2014.01.041
Database	NAL-Catalogue (AGRICOLA)

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Article: Recombinant lipidated dengue-3 envelope protein domain III stimulates broad immune responses in mice

Chiang, Chen-Yi / Chih-Hsiang Leng / Chun-Hsiang Hsieh / Hsin-Wei Chen / Hsueh-Hung Liu / I.-Hua Chen / Jy-Ping Tsai / Mei-Yu Chen / Pele Chong / Shih-Jen Liu

Vaccine. 2016 Feb. 17, v. 34, no. 8

2016

Abstract: The linkage of an immunogen with a toll-like receptor ligand has great potential to induce highly potent immune responses with the initial features of antigen-presenting cell activation. In the current study, we expressed recombinant dengue-3 envelope ... ...

Abstract	The linkage of an immunogen with a toll-like receptor ligand has great potential to induce highly potent immune responses with the initial features of antigen-presenting cell activation. In the current study, we expressed recombinant dengue-3 envelope protein domain III (D3ED III) in lipidated form using an Escherichia coli-based system. The recombinant lipidated dengue-3 envelope protein domain III (LD3ED III) augments the expression levels of IL-12 family cytokines. LD3ED III-immunized mice enhance wide ranges of T cell responses as indicated by IFN-γ, IL-17, IL-21 production. Additionally, LD3ED III-immunized mice increase the frequencies of anti-D3ED III antibody producing cells. The boosted antibody titers cover various IgG isotypes, including IgG1, IgG2a, IgG2b, and IgG3. Importantly, LD3ED III-immunized mice induce neutralizing antibody capacity associated with a reduction of viremia levels after challenges. In contrast, mice that are immunized with D3ED III formulated with aluminum phosphate (D3ED III/Alum) only enhance Th2 responses and boost IgG1 antibody titers. Neither neutralizing antibody responses nor the inhibition of viremia levels after challenge is observed in mice that are immunized with D3ED III/Alum. These results suggest that LD3ED III can induce broad profiles of cellular and humoral immune responses.
Keywords	alum ; aluminum phosphate ; antigens ; humoral immunity ; immune response ; immunoglobulin G ; interferon-gamma ; interleukin-12 ; interleukin-17 ; interleukin-21 ; ligands ; mice ; neutralizing antibodies ; T-lymphocytes ; Toll-like receptors ; vaccines ; viremia
Language	English
Dates of publication	2016-0217
Size	p. 1054-1061.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2016.01.009
Database	NAL-Catalogue (AGRICOLA)

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