Publications by authors named "Yu Chen Wu"

23 Publications

  • Page 1 of 1

Higher CD4/CD8 ratio of pleural effusion predicts better survival for lung cancer patients receiving immune checkpoint inhibitors.

Sci Rep 2021 Apr 30;11(1):9381. Epub 2021 Apr 30.

Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Pleural effusion is a rare immune-related adverse event for lung cancer patients receiving immune checkpoint inhibitors (ICIs). We enrolled 281 lung cancer patients treated with ICIs and 17 were analyzed. We categorized the formation of pleural effusion into 3 patterns: type 1, rapid and massive; type 2, slow and indolent; and type 3, with disease progression. CD4/CD8 ratio of 1.93 was selected as the cutoff threshold to predict survival. Most patients of types 1 and 2 effusions possessed pleural effusion with CD4/CD8 ratios ≥ 1.93. The median OS time in type 1, 2, and 3 patients were not reached, 24.8, and 2.6 months, respectively. The median PFS time in type 1, 2, and 3 patients were 35.5, 30.2, and 1.4 months, respectively. The median OS for the group with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were not reached and 2.6 months. The median PFS of those with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were 18.4 and 1.2 months. In conclusion, patients with type 1 and 2 effusion patterns had better survival than those with type 3. Type 1 might be interpreted as pseudoprogression of malignant pleural effusion. CD4/CD8 ratio ≥ 1.93 in pleural effusion is a good predicting factor for PFS.
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http://dx.doi.org/10.1038/s41598-021-89043-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087817PMC
April 2021

Binary Self-Assembly of Nanocolloidal Arrays using Concurrent and Sequential Spin Coating Techniques.

Materials (Basel) 2021 Jan 7;14(2). Epub 2021 Jan 7.

Department of Mechanical Engineering, Chang Gung University, Taoyuan 33302, Taiwan.

This paper reports the binary colloid assembly of nanospheres using spin coating techniques. Polystyrene spheres with sizes of 900 and 100 nm were assembled on top of silicon substrates utilizing a spin coater. Two different spin coating processes, namely concurrent and sequential coatings, were employed. For the concurrent spin coating, 900 and 100 nm colloidal nanospheres of latex were first mixed and then simultaneously spin coated onto the silicon substrate. On the other hand, the sequential coating process first created a monolayer of a 900 nm nanosphere array on the silicon substrate, followed by the spin coating of another layer of a 100 nm colloidal array on top of the 900 nm array. The influence of the processing parameters, including the type of surfactant, spin speed, and spin time, on the self-assembly of the binary colloidal array were explored. The empirical outcomes show that by employing the optimal processing conditions, binary colloidal arrays can be achieved by both the concurrent and sequential spin coating processes.
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http://dx.doi.org/10.3390/ma14020274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827635PMC
January 2021

Opisthobranch grazing results in mobilisation of spherulous cells and re-allocation of secondary metabolites in the sponge Aplysina aerophoba.

Sci Rep 2020 12 14;10(1):21934. Epub 2020 Dec 14.

Marine Ecology, GEOMAR Helmholtz Centre for Ocean Research, Düsternbrooker Weg 20, 24105, Kiel, Germany.

Sponges thrive in marine benthic communities due to their specific and diverse chemical arsenal against predators and competitors. Yet, some animals specifically overcome these defences and use sponges as food and home. Most research on sponge chemical ecology has characterised crude extracts and investigated defences against generalist predators like fish. Consequently, we know little about chemical dynamics in the tissue and responses to specialist grazers. Here, we studied the response of the sponge Aplysina aerophoba to grazing by the opisthobranch Tylodina perversa, in comparison to mechanical damage, at the cellular (via microscopy) and chemical level (via matrix-assisted laser desorption/ionization imaging mass spectrometry, MALDI-imaging MS). We characterised the distribution of two major brominated alkaloids in A. aerophoba, aerophobin-2 and aeroplysinin-1, and identified a generalised wounding response that was similar in both wounding treatments: (i) brominated compound-carrying cells (spherulous cells) accumulated at the wound and (ii) secondary metabolites reallocated to the sponge surface. Upon mechanical damage, the wound turned dark due to oxidised compounds, causing T. perversa deterrence. During grazing, T. perversa's way of feeding prevented oxidation. Thus, the sponge has not evolved a specific response to this specialist predator, but rather relies on rapid regeneration and flexible allocation of constitutive defences.
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http://dx.doi.org/10.1038/s41598-020-78667-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736331PMC
December 2020

3D Printing of Amino Resin-based Photosensitive Materials on Multi-parameter Optimization Design for Vascular Engineering Applications.

Polymers (Basel) 2019 Aug 24;11(9). Epub 2019 Aug 24.

3D Printing Medical Research Center, China Medical University Hospital, Taichung 40447, Taiwan.

Cardiovascular diseases are currently the most common cause of death globally and of which, the golden treatment method for severe cardiovascular diseases or coronary artery diseases are implantations of synthetic vascular grafts. However, such grafts often come with rejections and hypersensitivity reactions. With the emergence of regenerative medicine, researchers are now trying to explore alternative ways to produce grafts that are less likely to induce immunological reactions in patients. The main goal of such studies is to produce biocompatible artificial vascular grafts with the capability of allowing cellular adhesion and cellular proliferation for tissues regeneration. The Design of Experimental concepts is employed into the manufacturing process of digital light processing (DLP) 3D printing technology to explore near-optimal processing parameters to produce artificial vascular grafts with vascular characteristics that are close to native vessels by assessing for the cause and effect relationships between different ratios of amino resin (AR), 2-hydroxyethyl methacrylate (HEMA), dopamine, and curing durations. We found that with proper optimization of fabrication procedures and ratios of materials, we are able to successfully fabricate vascular grafts with good printing resolutions. These had similar physical properties to native vessels and were able to support cellular adhesion and proliferation. This study could support future studies in exploring near-optimal processes for fabrication of artificial vascular grafts that could be adapted into clinical applications.
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http://dx.doi.org/10.3390/polym11091394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780824PMC
August 2019

Clinicopathologic features and prognostic value of KRAS, NRAS and BRAF mutations and DNA mismatch repair status: A single-center retrospective study of 1,834 Chinese patients with Stage I-IV colorectal cancer.

Int J Cancer 2019 09 22;145(6):1625-1634. Epub 2019 Jun 22.

Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Mutations of KRAS, NRAS, BRAF and DNA mismatch repair (MMR) status have become an important part of the assessment of patients with colorectal cancer (CRC), while respective clinicopathologic features and prognostic significance in specific stages and related detection strategies remain unclear. We retrospectively analyzed clinicopathologic features and prognosis of 1,834 patients with Stage I-IV colorectal adenocarcinoma. Mutations in KRAS, NRAS and BRAF and DNA MMR status were determined. The mutation rates of KRAS, NRAS and BRAF were 46.4, 3.2 and 3.5%, respectively, and the mismatch repair gene deletion (dMMR) rate was 5.6%. In a multivariate analysis, female, advanced age, tumor type histology, mucinous carcinoma and positive tumor deposits were associated with a high KRAS mutation rate. A high BRAF mutation rate was associated with female, poor differentiation, lymphovascular invasion and positive tumor deposits. Factors associated with high dMMR rates included low age, large tumor size, poor differentiation, Stages I-III. Tumor site was independently associated with KRAS mutation, BRAF mutation and dMMR. KRAS and BRAF mutations were independent risk factors for shorter overall survival (OS) in Stage IV tumors but not in Stage I-III tumors. NRAS mutation was an independent risk factor for shorter OS in Stage I-II tumors. dMMR was independently associated with longer OS in Stage III tumors.
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http://dx.doi.org/10.1002/ijc.32489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771586PMC
September 2019

Sponges from Zanzibar host diverse prokaryotic communities with potential for natural product synthesis.

FEMS Microbiol Ecol 2019 04;95(4)

Institute for Chemistry and Biology of the Marine Environment, Carl-von-Ossietzky University Oldenburg, Schleusenstr. 1, 26382 Wilhelmshaven, Germany.

Sponges are one of the most dominant organisms in marine ecosystems. One reason for their success is their association with microorganisms that are besides the host itself responsible for the chemical defence. Sponge abundances have been increasing on coral reefs in the Western Indian Ocean (WIO) and are predicted to increase further with rising anthropogenic impacts on coral reefs. However, there is a paucity of information on chemical ecology of sponges from the WIO and their prokaryotic community composition. We used a combination of Illumina sequencing and a predictive metagenomic analysis to (i) assess the prokaryotic community composition of sponges from Zanzibar, (ii) predict the presence of KEGG metabolic pathways responsible for bioactive compound production and (iii) relate their presence to the degree of observed chemical defence in their respective sponge host. We found that sponges from Zanzibar host diverse prokaryotic communities that are host species-specific. Sponge-species and respective specimens that showed strong chemical defences in previous studies were also predicted to be highly enriched in various pathways responsible for secondary metabolite production. Hence, the combined sequencing and predictive metagenomic approach proved to be a useful indicator for the metabolic potential of sponge holobionts.
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http://dx.doi.org/10.1093/femsec/fiz026DOI Listing
April 2019

Fueled by methane: deep-sea sponges from asphalt seeps gain their nutrition from methane-oxidizing symbionts.

ISME J 2019 05 15;13(5):1209-1225. Epub 2019 Jan 15.

Max Planck Institute for Marine Microbiology, Celsiusstrasse 1, 28359, Bremen, Germany.

Sponges host a remarkable diversity of microbial symbionts, however, the benefit their microbes provide is rarely understood. Here, we describe two new sponge species from deep-sea asphalt seeps and show that they live in a nutritional symbiosis with methane-oxidizing (MOX) bacteria. Metagenomics and imaging analyses revealed unusually high amounts of MOX symbionts in hosts from a group previously assumed to have low microbial abundances. These symbionts belonged to the Marine Methylotrophic Group 2 clade. They are host-specific and likely vertically transmitted, based on their presence in sponge embryos and streamlined genomes, which lacked genes typical of related free-living MOX. Moreover, genes known to play a role in host-symbiont interactions, such as those that encode eukaryote-like proteins, were abundant and expressed. Methane assimilation by the symbionts was one of the most highly expressed metabolic pathways in the sponges. Molecular and stable carbon isotope patterns of lipids confirmed that methane-derived carbon was incorporated into the hosts. Our results revealed that two species of sponges, although distantly related, independently established highly specific, nutritional symbioses with two closely related methanotrophs. This convergence in symbiont acquisition underscores the strong selective advantage for these sponges in harboring MOX bacteria in the food-limited deep sea.
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http://dx.doi.org/10.1038/s41396-019-0346-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474228PMC
May 2019

A negative-doughnut distal resection margin less than 5 mm does not affect prognosis in rectal cancer.

J Surg Oncol 2018 Sep;118(3):536-543

Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Aim: Many issues relating to the distal margin of anterior resection of the rectum still exist. We aimed to investigate whether negative distal resection margin (DRM) and positive DRM in the main specimen with negative doughnut has equivalent prognosis in patients with rectal cancer.

Methods: We included 287 patients with rectal cancer, including 69 cases with positive margins and 218 cases with negative margins, all of whom underwent regular follow-up. Survival rate was calculated using Kaplan-Meier survival analysis, while the log-rank test was used to determine statistical difference. Prognostic factors were found using the Cox regression model.

Results: There was no significant difference in clinicopathological features between the two groups with the exception of tumor location. Positive findings in the DRM with negative findings in the doughnut resection do not affect the overall survival, local recurrence, or distant metastasis. Factors relating to resection margin, such as the length of resection, negative, or positive findings, were not found to be prognostic.

Conclusion: Given postoperative pathology results with positive DRM but negative findings in the doughnut resection, a second surgery was not necessary. Instead, adjuvant radiochemotherapy and close follow-up will suffice.
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http://dx.doi.org/10.1002/jso.25161DOI Listing
September 2018

[Effects of biochar application on the abundance and structure of ammonia-oxidizer communities in coal-mining area.]

Ying Yong Sheng Tai Xue Bao 2017 Oct;28(10):3417-3423

Anhui Province Key Labrotory of Resource and Plant Biology, College of Life Science, Huaibei Normal University, Huaibei 235000, Anhui, China.

As a new type of soil amendment, biochar can effectively improve soil fertility, structure and soil nitrogen transformation. We studied the effects of biochar application on soil properties, abundance and community structure of ammonia oxidizer in coal-mining area. The results showed that the biochar application significantly increased contents of soil NH4+-N, total nitrogen, available phosphorus and potassium. Compared with the control, no change in the abundance of ammonia-oxidizing archaea (AOA) was found under biochar treatment, but there was a significant increase in the abundance of ammonia-oxidizing bacteria (AOB). The analysis of T-RFLP profiles showed that biochar significantly increased the diversity indexes of AOA and AOB, and altered the community structure of both AOA and AOB. Improved soil nutrients as well as increased abundance and diversity of ammonia-oxidizing community to some extent indicated the potential of biochar application in reclamation of coal-mining area soil.
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http://dx.doi.org/10.13287/j.1001-9332.201710.034DOI Listing
October 2017

Association between Internet gaming disorder and generalized anxiety disorder.

J Behav Addict 2017 Dec;6(4):564-571

3 Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung City, Taiwan.

Introduction This study evaluates the association between generalized anxiety disorder (GAD) and Internet gaming disorder (IGD) and the role of behavior inhibition in young adults. Methods We recruited 87 people with IGD and a control group of 87 people without a history of IGD. All participants underwent a diagnostic interview based on the fifth edition of Diagnostic and Statistical Manual of Mental Disorders, IGD and GAD criteria, and completed a questionnaire on behavior inhibition, depression, and anxiety. Results Logistic regression revealed that adults with GAD were more likely (odds ratio = 8.11, 95% CI = 1.78-37.09) to have IGD than those without it. The OR decreased when controlling for behavior inhibition. IGD subjects with GAD had higher depressive and anxiety score than those without GAD. Conclusions GAD was associated with IGD. Comorbid GAD can contribute to higher emotional difficulty. GAD should be well-assessed and interventions planned when treating young adults with IGD. Behavioral inhibition confounds the association between GAD and IGD. Further study is necessary to evaluate how to intervene in behavioral inhibitions to attenuate the risk of GAD and IGD comorbidity.
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http://dx.doi.org/10.1556/2006.6.2017.088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034959PMC
December 2017

Predicting the HMA-LMA Status in Marine Sponges by Machine Learning.

Front Microbiol 2017 8;8:752. Epub 2017 May 8.

RD3 Marine Microbiology, GEOMAR Helmholtz Centre for Ocean Research Kiel and Christian-Albrechts UniversityKiel, Germany.

The dichotomy between high microbial abundance (HMA) and low microbial abundance (LMA) sponges has been observed in sponge-microbe symbiosis, although the extent of this pattern remains poorly unknown. We characterized the differences between the microbiomes of HMA ( = 19) and LMA ( = 17) sponges (575 specimens) present in the Sponge Microbiome Project. HMA sponges were associated with richer and more diverse microbiomes than LMA sponges, as indicated by the comparison of alpha diversity metrics. Microbial community structures differed between HMA and LMA sponges considering Operational Taxonomic Units (OTU) abundances and across microbial taxonomic levels, from phylum to species. The largest proportion of microbiome variation was explained by the host identity. Several phyla, classes, and OTUs were found differentially abundant in either group, which were considered "HMA indicators" and "LMA indicators." Machine learning algorithms (classifiers) were trained to predict the HMA-LMA status of sponges. Among nine different classifiers, higher performances were achieved by Random Forest trained with phylum and class abundances. Random Forest with optimized parameters predicted the HMA-LMA status of additional 135 sponge species (1,232 specimens) without knowledge. These sponges were grouped in four clusters, from which the largest two were composed of species consistently predicted as HMA ( = 44) and LMA ( = 74). In summary, our analyses shown distinct features of the microbial communities associated with HMA and LMA sponges. The prediction of the HMA-LMA status based on the microbiome profiles of sponges demonstrates the application of machine learning to explore patterns of host-associated microbial communities.
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http://dx.doi.org/10.3389/fmicb.2017.00752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421222PMC
May 2017

Valproic Acid and Lithium Meditate Anti-Inflammatory Effects by Differentially Modulating Dendritic Cell Differentiation and Function.

J Cell Physiol 2017 05 10;232(5):1176-1186. Epub 2016 Nov 10.

School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan.

Valproic acid (VPA), with inhibition activity mainly toward histone deacetylase (HDAC) and Glycogen Synthase Kinase (GSK)-3, and lithium, with inhibition activity mainly toward GSK-3, are both prescribed in clinical as mood-stabilizers and anticonvulsants for the control of bipolar disorder. This study aims to compare the immuno-modulation activities of VPA and lithium, especially on the differentiation and functions of dendritic cells (DC). Our data show that treatment with VPA or lithium effectively alleviated the severity of collagen-induced arthritis triggered by LPS in mice. Both agents reduced the serum level of IL-6 and IL-10 after LPS challenge in mice. VPA and lithium both induce significant down-regulation of group I CD1 expression and secretion of IL-6 during differentiation of human monocyte-derived immature DC, while they differ in the induction of CD83 and CD86 expression, secretion of IL-8, IL-10, and TNF-α. Upon stimulation of immature DC with LPS, VPA, and lithium both reduced the secretion of IL-6 and TNF-α. However, only lithium significantly increased the production of IL-10, while VPA increased the production of IL-8 but substantially reduce the secretion of IL-10 and IL-23. Treatment with VPA resulted in a reduced capacity of LPS-stimulated DC to promote the differentiation of T helper 17 cells that are critical in the promotion of inflammatory responses. Taken together, our results suggest that VPA and lithium may differentially modulate inflammation through regulating the capacity of DC to mediate distinct T cell responses, and they may provide a complementary immunomodulatory effects for the treatment of inflammation-related diseases. J. Cell. Physiol. 232: 1176-1186, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jcp.25604DOI Listing
May 2017

A phase I clinical study of immunotherapy for advanced colorectal cancers using carcinoembryonic antigen-pulsed dendritic cells mixed with tetanus toxoid and subsequent IL-2 treatment.

J Biomed Sci 2016 Aug 24;23(1):64. Epub 2016 Aug 24.

National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.

Background: To better evaluate and improve the efficacy of dendritic cell (DC)-based cancer immunotherapy, we conducted a clinical study of patients with advanced colorectal cancer using carcinoembryonic antigen (CEA)-pulsed DCs mixed with tetanus toxoid and subsequent interleukin-2 treatment. The tetanus toxoid in the vaccine preparation serves as an adjuvant and provides a non-tumor specific immune response to enhance vaccine efficacy. The aims of this study were to (1) evaluate the toxicity of this treatment, (2) observe the clinical responses of vaccinated patients, and (3) investigate the immune responses of patients against CEA before and after treatment.

Methods: Twelve patients were recruited and treated in this phase I clinical study. These patients all had metastatic colorectal cancer and failed standard chemotherapy. We first subcutaneously immunized patients with metastatic colorectal cancer with 1 × 10(6) CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 10(6) CEA-pulsed DCs alone. Low-dose interleukin-2 was administered subcutaneously following the final DC vaccination to boost the growth of T cells. Patients were evaluated for adverse event and clinical status. Blood samples collected before, during, and after treatment were analyzed for T cell proliferation responses against CEA.

Results: No severe treatment-related side effects or toxicity was observed in patients who received the regular 4 DC vaccine injections. Two patients had stable disease and 10 patients showed disease progression. A statistically significant increase in proliferation against CEA by T cells collected after vaccination was observed in 2 of 9 patients.

Conclusions: The results of this study indicate that it is feasible and safe to treat colorectal cancer patients using this protocol. An increase in the anti-CEA immune response and a clinical benefit was observed in a small fraction of patients. This treatment protocol should be further evaluated in additional colorectal cancer patients with modifications to enhance T cell responses.

Trial Registration: ClinicalTrials.gov (identifier NCT00154713 ), September 8, 2005.
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http://dx.doi.org/10.1186/s12929-016-0279-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997699PMC
August 2016

Psychotropic effects of Lactobacillus plantarum PS128 in early life-stressed and naïve adult mice.

Brain Res 2016 Jan 24;1631:1-12. Epub 2015 Nov 24.

Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 11221, Taiwan; Probiotic Research Center, National Yang-Ming University, Taipei 11221, Taiwan. Electronic address:

Ingestion of specific probiotics, namely "psychobiotics", produces psychotropic effects on behavior and affects the hypothalamic-pituitary-adrenal axis and neurochemicals in the brain. We examined the psychotropic effects of a potential psychobiotic bacterium, Lactobacillus plantarum strain PS128 (PS128), on mice subjected to early life stress (ELS) and on naïve adult mice. Behavioral tests revealed that chronic ingestion of PS128 increased the locomotor activities in both ELS and naïve adult mice in the open field test. In the elevated plus maze, PS128 significantly reduced the anxiety-like behaviors in naïve adult mice but not in the ELS mice; whereas the depression-like behaviors were reduced in ELS mice but not in naïve mice in forced swimming test and sucrose preference test. PS128 administration also reduced ELS-induced elevation of serum corticosterone under both basal and stressed states but had no effect on naïve mice. In addition, PS128 reduced inflammatory cytokine levels and increased anti-inflammatory cytokine level in the serum of ELS mice. Furthermore, the dopamine level in the prefrontal cortex (PFC) was significantly increased in PS128 treated ELS and naïve adult mice whereas serotonin (5-HT) level was increased only in the naïve adult mice. These results suggest that chronic ingestion of PS128 could ameliorate anxiety- and depression-like behaviors and modulate neurochemicals related to affective disorders. Thus PS128 shows psychotropic properties and has great potential for improving stress-related symptoms.
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http://dx.doi.org/10.1016/j.brainres.2015.11.018DOI Listing
January 2016

Simultaneous determination of ten preservatives in ten kinds of foods by micellar electrokinetic chromatography.

Food Chem 2015 Aug 24;181:207-14. Epub 2015 Feb 24.

College of Science, Agricultural University of Hebei, Baoding 071001, China. Electronic address:

An improved micellar electrokinetic capillary chromatography method (MEKC) for the simultaneous determination of ten preservatives in ten different kinds of food samples was reported. An uncoated fused-silica capillary with 50 μm i.d. and 70 cm total length was used. Under the optimized conditions, the linear response was observed in the range of 1.2-200mg/L for the analytes. The limits of detection (LOD, S/N=3) and limits of quantitation (LOQ, S/N=10) ranging from 0.4 to 0.5mg/L and 1.2 to 1.5mg/L, respectively were obtained. The method was used for the determination of sorbic and benzoic acids in two FAPAS® (Food Analysis Performance Assessment Scheme) proficiency test samples (jam and chocolate cake). The results showed that the current method with simple sample pretreatment and small reagent consumption could meet the needs for routine analysis of the ten preservatives in ten types of food products.
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http://dx.doi.org/10.1016/j.foodchem.2015.02.060DOI Listing
August 2015

Numerical investigation of one-dimensional nonpolarizing guided-mode resonance gratings with conformal dielectric films.

Opt Express 2013 Jan;21(1):345-57

Institute of Optometry and Ophthalmology, Wenzhou Medical College, Wenzhou, China.

We present the nonpolarizing resonance properties of two types of one-dimensional (1D) guided-mode resonance (GMR) gratings consisting of the sinusoidal-profile grating substrate and the conformal dielectric thin films. The optimization with respect to the grating height and the phase of the conformal graded-index layer is important for the design of nonpolarizing type-I GMR gratings. The thin films design of the conformal step-index multilayer and the optimization with respect to the grating height are of two critical steps to obtain the nonpolarizing type-II GMR gratings. Both of the two types of nonpolarizing GMR gratings can be designed to support single-mode resonance and multimode resonance under normal incidence.
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http://dx.doi.org/10.1364/OE.21.000345DOI Listing
January 2013

Surface expression of HLA-G is involved in mediating immunomodulatory effects of placenta-derived multipotent cells (PDMCs) towards natural killer lymphocytes.

Cell Transplant 2011 9;20(11-12):1721-30. Epub 2011 Jun 9.

National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.

Interactions between maternal natural killer lymphocytes (NKs) and fetal tissues are important in mediating maternal-fetal tolerance. We therefore investigated the interactions of NKs to placenta-derived multipotent cells (PDMCs) isolated from the term human placenta. PDMCs have similar cell surface marker expression as bone marrow mesenchymal stem cells (BMMSCs) and additionally express human embryonic stem cell markers SSEA-4 and CD-9. Differentiation into the tri-mesodermal lineages of osteoblastic, adipocytic, and chondrogenic phenotypes can be readily achieved under the appropriate conditions. We found that PDMCs are more resistant to NK-mediated lysis than the major histocompatibility complex (MHC) class-I null target cell K562, and can suppress NK secretion of interferon-γ (IFN-γ). Moreover, as third-party cells, PDMCs suppressed the cytotoxic effects of cytokine-stimulated NKs on K562. Pretreatment of PDMCs with IFN-γ, a proinflammatory cytokine, surprisingly enhanced such immunosuppressive effects. Cell-cell contact between NKs and PDMCs is required for suppressive effects, which are partially mediated by slight upregulation of the NK inhibitory receptor killer inhibitory receptor and downregulation of the activating receptor NKp30. Moreover, enhancement of PDMC suppressive effects is also mediated by IFN-γ-induced surface expression of HLA-G--an immunomodulatory nonclassical MHC class I molecule--on PDMCs, as seen by partial reversibility with HLA-G neutralizing antibodies. With its broad immunosuppressive properties, PDMCs may represent a potential cell source for therapeutic use.
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http://dx.doi.org/10.3727/096368911X580590DOI Listing
June 2013

Modulation of the development of human monocyte-derived dendritic cells by lithium chloride.

J Cell Physiol 2011 Feb;226(2):424-33

National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.

Lithium has been used or explored to treat psychiatric and neurodegenerative diseases that are frequently associated with an abnormal immune status. It is likely that lithium may work through modulation of immune responses in these patients. Because dendritic cells (DC) play a central role in regulating immune responses, this study investigated the influence of lithium chloride (LiCl) on the development and function of DC. Exposure to LiCl during the differentiation of human monocyte-derived immature DCs (iDC) enhances CD86 and CD83 expression and increases the production of IL-1β, IL-6, IL-8, IL-10, and TNF-α. However, the presence of LiCl during LPS-induced maturation of iDC has the opposite effect. During iDC differentiation, LiCl suppresses the activity of glycogen synthase kinase (GSK)-3β, and activates PI3K and MEK. In addition, LiCl activates peroxisome proliferator-activated receptor γ (PPARγ) during iDC differentiation, a pathway not described before. Each of these signaling pathways appears to have distinct impact on the differentiating iDC. The enhanced CD86 expression by LiCl involves the PI3K/AKT and GSK-3β pathway. LiCl modulates the expression of CD83 in iDC mainly through MEK/ERK, PI3K/AKT, and PPARγ pathways, while the increased production of IL-1β and TNF-α mainly involves the MEK/ERK pathway. The effect of LiCl on IL-6/IL-8/IL-10 secretion in iDC is mediated through inhibition of GSK-3β. We have also demonstrated that PPARγ is downstream of GSK-3β and is responsible for the LiCl-mediated modulation of CD86/83 and CD1 expression, but not IL-6/8/10 secretion. The combined influence of these molecular signaling pathways may account for certain clinical effect of lithium.
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http://dx.doi.org/10.1002/jcp.22348DOI Listing
February 2011

Sesamin inhibits macrophage-induced vascular endothelial growth factor and matrix metalloproteinase-9 expression and proangiogenic activity in breast cancer cells.

Inflammation 2011 Jun;34(3):209-21

National Institute of Cancer Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County, 350, Taiwan, Republic of China.

Sesamin is a sesame component with antihypertensive and antioxidative activities and has recently aroused much interest in studying its potential anticancer application. Macrophage is one of the infiltrating inflammatory cells in solid tumor and may promote tumor progression via enhancement of tumor angiogenesis. In this study, we investigated whether sesamin inhibited macrophage-enhanced proangiogenic activity of breast cancer cell lines MCF-7 and MDA-MB-231. Using vascular endothelial cell capillary tube and network formation assays, both breast cancer cell lines exhibited elevated proangiogenic activities after coculture with macrophages or pretreatment with macrophage-conditioned medium. This elevation of proangiogenic activity was drastically suppressed by sesamin. Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) induced by macrophages in both cell lines were also inhibited by sesamin. Nuclear levels of HIF-1α and NF-κB, important transcription factors for VEGF and MMP-9 expression, respectively, were obviously reduced by sesamin. VEGF induction by macrophage in MCF-7 cells was shown to be via ERK, JNK, phosphatidylinositol 3-kinase, and NF-κB-mediated pathways. These signaling molecules and additional p38(MAPK) were also involved in macrophage-induced MMP-9 expression. Despite such diverse pathways were induced by macrophage, only Akt and p38(MAPK) activities were potently inhibited by sesamin. Expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-α were substantially increased and involved in macrophage-induced VEGF and MMP-9 mRNA expression in MCF-7 cells. Sesamin effectively inhibited the expression of these cytokines to avoid the reinforced induction of VEGF and MMP-9. In conclusion, sesamin potently inhibited macrophage-enhanced proangiogenic activity of breast cancer cells via inhibition of VEGF and MMP-9 induction.
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http://dx.doi.org/10.1007/s10753-010-9226-zDOI Listing
June 2011

Isoquinolinium salts from o-halobenzaldehydes, amines, and alkynes catalyzed by nickel complexes: synthesis and applications.

Chemistry 2009 Oct;15(41):10727-31

Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan.

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http://dx.doi.org/10.1002/chem.200901366DOI Listing
October 2009

Conditioning vaccination site with irradiated MIP-3alpha-transfected tumor cells enhances efficacy of dendritic cell-based cancer vaccine.

J Immunother 2009 May;32(4):363-9

National Institute of Cancer Research, National Health Research Institutes, 367 Sheng Li Road, Tainan 704, Taiwan.

Macrophage inflammation protein-3alpha (MIP-3alpha) is a chemokine expressed in inflamed tissue and capable of inducing migration of immature dendritic cells (DCs) or Langerhans cells. We postulated that conditioning vaccination sites with MIP-3alpha might enhance the efficacy of subsequently administered DC-based cancer vaccines. Our results demonstrate that subcutaneously injection of irradiated tumor cells expressing MIP-3alpha induces substantial cell infiltration to the injection site. Vaccination of irradiated tumor cells expressing MIP-3alpha followed by DCs pulsed with irradiated tumor cells can effectively suppress tumor growth in animals, which is significantly better than vaccination with irradiated MIP-3alpha-producing tumor cells or DCs pulsed with tumor cells alone. The protective effect was most evident when the MIP-3alpha-producing tumor cells and DC-based vaccines were injected at the same site. These results support the notion that this combination vaccination strategy might generate a more effective immune response to suppress the growth of tumor cells in animals.
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http://dx.doi.org/10.1097/CJI.0b013e31819d29d8DOI Listing
May 2009

A pilot clinical trial of vaccination with dendritic cells pulsed with autologous tumor cells derived from malignant pleural effusion in patients with late-stage lung carcinoma.

Cancer 2005 Feb;103(4):763-71

Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

Background: The authors conducted a pilot clinical trial to explore the vaccination of patients with late-stage lung carcinoma with dendritic cells (DCs) pulsed with necrotic tumor cells derived from malignant pleural effusion specimens, and to evaluate the antitumor immune response induced by this therapy.

Methods: Autologous DCs were generated by culturing adherent mononuclear cells with interleukin-4 and granulocyte-macrophage-colony-stimulating factor for 7 days. Day-7 DCs were cocultured overnight with autologous necrotic tumor cells derived from pleural effusion specimens to allow internalization of tumor antigens. DCs were then treated with tumor necrosis factor-alpha for 16 hours. The antigen-loaded DCs were injected into each patient's inguinal lymph nodes under sonographic guidance. Eight patients with late-stage nonsmall cell lung carcinoma were treated in this manner. Patients were vaccinated once weekly for 4 weeks and then boosted twice biweekly.

Results: The authors found that there was no Grade II/III toxicity and autoimmune response in all patients after intranodal injection of the DC vaccine. Minor to moderate increases in T-cell responses against tumor antigens were observed after DC vaccination in six of eight patients. Five patients had progressive disease. One patient had minor tumor response and two patients had stable disease. The two patients who had longer disease control also had better T-cell responses.

Conclusions: The results indicated that it was feasible to immunize patients with lung carcinoma intranodally with DCs pulsed with necrotic tumor cells enriched from pleural effusion specimens, and this approach may generate T-cell responses and provide clinical benefit in some patients.
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http://dx.doi.org/10.1002/cncr.20843DOI Listing
February 2005

Generation of carcinoembryonic antigen (CEA)-specific T-cell responses in HLA-A*0201 and HLA-A*2402 late-stage colorectal cancer patients after vaccination with dendritic cells loaded with CEA peptides.

Clin Cancer Res 2004 Apr;10(8):2645-51

Cancer Research Cooperative Laboratory at the National Taiwan University Hospital, Division of Cancer Research, National Health Research Institutes, Taipei, Republic of China.

Purpose: We intranodally immunized metastatic colorectal carcinoma patients, who had failed standard chemotherapy, with dendritic cells (DCs) pulsed with HLA-A*0201- or HLA-A*2402-restricted carcinoembryonic antigen (CEA) peptides to evaluate the safety of this treatment and the immune response against CEA peptides before and after the treatment.

Experimental Design: Six patients with the HLA-A*2402 genotype and 4 patients with the HLA-A*0201 genotype were enrolled. A single CEA peptide (YLSGANLNL) or two CEA peptides (QYSWFVNGTF and TYACFVSNL) were used for patients with the HLA-A*0201 or HLA-A*2402 genotype, respectively. Autologous DCs were generated by culturing adherent mononuclear cells with interleukin 4 and granulocyte macrophage colony-stimulating factor for 6 days. Maturation of DCs was then induced with tumor necrosis factor alpha for 40 h. Mature DCs were pulsed with appropriate CEA peptides for 2 h. After washing, 1 million peptide-pulsed DCs were injected into one inguinal lymph node under sonographic guidance. Each patient received four injections.

Results: No grade II/III toxicity or autoimmunity was observed. An increase in the number of CEA-specific T cells after DC vaccination could be detected in 7 of 10 (70%) patients. Two (20%) patients had stable disease for at least 12 weeks. One of these 2 patients experienced a transient decrease in CEA levels during the treatment period and also had the most significant T-cell response against the immunizing CEA peptides.

Conclusions: These results suggest that our vaccination procedure can generate or boost specific T-cell responses and may provide clinical benefit in certain cancer patients.
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http://dx.doi.org/10.1158/1078-0432.ccr-03-0430DOI Listing
April 2004
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