Publications by authors named "Yu-Fang Huang"

74 Publications

Targeting the Copper Transport System to Improve Treatment Efficacies of Platinum-Containing Drugs in Cancer Chemotherapy.

Pharmaceuticals (Basel) 2021 Jun 8;14(6). Epub 2021 Jun 8.

Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.

The platinum (Pt)-containing antitumor drugs including cisplatin (cis-diamminedichloroplatinum II, cDDP), carboplatin, and oxaliplatin, have been the mainstay of cancer chemotherapy. These drugs are effective in treating many human malignancies. The major cell-killing target of Pt drugs is DNA. Recent findings underscored the important roles of Pt drug transport system in cancer therapy. While many mechanisms have been proposed for Pt-drug transport, the high-affinity copper transporter (hCtr1), Cu chaperone (Atox1), and Cu exporters (ATP7A and ATP7B) are also involved in cDDP transport, highlighting Cu homeostasis regulation in Pt-based cancer therapy. It was demonstrated that by reducing cellular Cu bioavailable levels by Cu chelators, hCtr1 is transcriptionally upregulated by transcription factor Sp1, which binds the promoters of Sp1 and hCtr1. In contrast, elevated Cu poisons Sp1, resulting in suppression of hCtr1 and Sp1, constituting the Cu-Sp1-hCtr1 mutually regulatory loop. Clinical investigations using copper chelator (trientine) in carboplatin treatment have been conducted for overcoming Pt drug resistance due in part to defective transport. While results are encouraging, future development may include targeting multiple steps in Cu transport system for improving the efficacies of Pt-based cancer chemotherapy. The focus of this review is to delineate the mechanistic interrelationships between Cu homeostasis regulation and antitumor efficacy of Pt drugs.
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http://dx.doi.org/10.3390/ph14060549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227247PMC
June 2021

Prenatal Bisphenol a Exposure, DNA Methylation, and Low Birth Weight: A Pilot Study in Taiwan.

Int J Environ Res Public Health 2021 06 7;18(11). Epub 2021 Jun 7.

Institute of Environmental and Occupational Health Sciences, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.

Prenatal exposure to bisphenol A (BPA) may increase the risk of abnormal birth outcomes, and DNA methylation might mediate these adverse effects. This study aimed to investigate the effects of maternal BPA exposure on maternal and fetal DNA methylation levels and explore whether epigenetic changes are related to the associations between BPA and low birth weight. We collected urine and blood samples originating from 162 mother-infant pairs in a Taiwanese cohort study. We measured DNA methylation using the Illumina Infinium HumanMethylation 450 BeadChip in 34 maternal blood samples with high and low BPA levels based on the 75th percentile level (9.5 μg/g creatinine). Eighty-seven CpGs with the most differentially methylated probes possibly interacting with BPA exposure or birth weight were selected using two multiple regression models. Ingenuity pathway analysis (IPA) was utilized to narrow down 18 candidate CpGs related to disease categories, including developmental disorders, skeletal and muscular disorders, skeletal and muscular system development, metabolic diseases, and lipid metabolism. We then validated these genes by pyrosequencing, and 8 CpGs met the primer design score requirements in 82 cord blood samples. The associations among low birth weight, BPA exposure, and DNA methylation were analyzed. Exposure to BPA was associated with low birth weight. Analysis of the epigenome-wide findings did not show significant associations between BPA and DNA methylation in cord blood of the 8 CpGs. However, the adjusted odds ratio for the dehydrogenase/reductase member 9 (DHRS9) gene, at the 2nd CG site, in the hypermethylated group was significantly associated with low birth weight. These results support a role of BPA, and possibly DHRS9 methylation, in fetal growth. However, additional studies with larger sample sizes are warranted.
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http://dx.doi.org/10.3390/ijerph18116144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201193PMC
June 2021

Acute Invasive Fungal Rhinosinusitis-Related Orbital Infection: A Single Medical Center Experience.

J Ophthalmol 2021 12;2021:9987871. Epub 2021 Jun 12.

Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan.

Backgrounds: Acute invasive fungal rhinosinusitis (AIFRS) is a hazardous infectious disease with rapid progression and high mortality and morbidities. Further orbital involvement is commonly seen. This study aims to analyze risk factors, clinical characteristics, and outcomes between patients with or without orbital involvement.

Methods: A retrospective review was performed in a single tertiary medical center over a span of 13 years (2005-2018). A total of 21 patients with diagnosis of AIFRS were enrolled. We reviewed the patients' basic characteristics, comorbidities, clinical presentations, image study findings, culture pathogens, and treatment outcomes and analyzed the differences between orbital-involved and orbital sparing disease.

Results: The most common comorbidities in AIFRS were diabetes mellitus (DM) and hematological malignancy. Nine the 21 AIFRS patients had orbital-involved disease. Patients with orbital involvement had a higher prevalence of DM ( < 0.05). Image studies revealed significant infection of the ethmoid sinus, sphenoid sinus, and frontal sinus in the group with orbital complication ( < 0.05). , and were cultured in both groups. Five patients in the orbital involvement group expired, with all of them having an initial presentation of conscious disturbance ( < 0.01). Rhino-orbital-cerebral fungal infection was noticed in 3 of the 5 expired patients.

Conclusion: In AIFRS patients, DM other than hematological malignancy was the main risk factor for orbital-involved disease. Patients with ethmoid, sphenoid, or frontal sinusitis had a higher possibility of orbital complication. Poor consciousness at initial presentation revealed highest possibility of rhino-orbital-cerebral fungal infection and led to death.
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http://dx.doi.org/10.1155/2021/9987871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214473PMC
June 2021

COL11A1 activates cancer-associated fibroblasts by modulating TGF-β3 through the NF-κB/IGFBP2 axis in ovarian cancer cells.

Oncogene 2021 Jul 11;40(26):4503-4519. Epub 2021 Jun 11.

Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Ovarian cancer has a unique tumor microenvironment (TME) that enables cancer-associated fibroblasts (CAFs) to interact with cellular and matrix constituents and influence tumor development and migration into the peritoneal cavity. Collagen type XI alpha 1 (COL11A1) is overexpressed in CAFs; therefore this study examines its role during CAF activation in epithelial ovarian cancer (EOC). Coculturing human ovarian fibroblasts (HOFs) with high COL11A1-expressing EOC cells or exposure to the conditioned medium of these cells prompted the expression of COL11A1 and CAF phenotypes. Conversely, coculturing HOFs with low COL11A1-expressing EOC cells or COL11A1-knockdown abrogated COL11A1 overexpression and secretion, in addition to CAF activation. Increased p-SP1 expression attributed to COL11A1-mediated extracellular signal-regulated kinase activation (ERK) induced p65 translocation into the nucleus and augmented its binding to the insulin-like growth factor binding protein 2 (IGFBP2) promoter, ultimately inducing TGF-β3 activation. The CAF-cancer cell crosstalk triggered interleukin-6 release, which in turn promoted EOC cell proliferation and invasiveness. These in vitro results were confirmed by in vivo findings in a mouse model, showing that COL11A1 overexpression in EOC cells promoted tumor formation and CAF activation, which was inhibited by TGF-β3 antibody. Human tumors with high TGF-β3 levels showed elevated expression of COL11A1 and IGFBP2, which was associated with poor survival. Our findings suggest the possibility that anti-TGF-β3 treatment strategy may be effective in targeting CAFs in COL11A1-positive ovarian tumors.
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http://dx.doi.org/10.1038/s41388-021-01865-8DOI Listing
July 2021

Simultaneous trace analysis of 10 benzophenone-type ultraviolet filters in fish through liquid chromatography-tandem mass spectrometry.

Environ Pollut 2021 May 5;286:117306. Epub 2021 May 5.

Department of Safety, Health and Environmental Engineering, National United University, Miaoli, Taiwan.

We developed and validated a trace analytical method for the simultaneous determination of 10 benzophenone (BP)-type ultraviolet filters (BPs; BP, BP-1, BP-2, BP-3, BP-8, 2-hydroxybenzophenone [2-OHBP], 4-hydroxybenzophenone [4-OHBP], 4-methylbenzophenone [4-MBP], methyl-2-benzoylbenzoate [M2BB], and 4-benzoylbiphenyl [PBZ]) to analyze BPs in 110 commercial fish samples. The quick, easy, cheap, effective, rugged, and safe (QuEChERS) technique coupled with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed. The developed method exhibited satisfactory linearity (R > 0.993), favorable precision with intraday and interday relative standard deviation ranges of 1.0%-26.6% and 2.3%-29.3%, respectively, and a limit of detection ranging from 0.001 to 0.1 ng/g. BP and 2-OHBP were detected in 100% of the samples; BP-3, 4-OHBP, PBZ, and 4-MBP were detected in >70% of the samples; M2BB was detected in 33% of the samples, and BP-2 and BP-8 were not detected. Higher mean (minimum-maximum) levels of 2-OHBP and BP were found in fish samples with low lipid content, ranging from 18 (1.1-218.3) to 10 (0.5-45.4) ng/g, and those with high lipid content, ranging from 22 (1.5-76.4) to 9.6 (5.2-18.5) ng/g; low levels of the remaining six BPs were found, ranging from 0.01 to 0.9 ng/g. The mean 2-OHBP levels were 21.3, 14.4, and 30.2 ng/g for fish samples obtained from aquaculture in Taiwan, the wild in Taiwan, and different countries, respectively, with levels up to 218.3 ng/g (field eel) for a sample from Indonesia. BPs may not pose a health risk to Taiwanese adults through the consumption of fish; however, additional studies are needed to examine the risk that these contaminants may pose to ecosystems and human health.
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http://dx.doi.org/10.1016/j.envpol.2021.117306DOI Listing
May 2021

Clinical Characteristics and Prognostic Analysis of Patients With Signet Ring Cell Gastric Carcinoma.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820983812

Department of Medical Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China.

We do not know the clinical and prognostic factors that influence the survival of patients with gastric signet ring cell carcinoma (SRC). Therefore, a retrospective review was undertaken of 219 patients with SRC who had undergone gastrectomy between January 2009 and December 2012 in our hospital. Patient age, sex, TNM stage, vessel carcinoma embolus, perineural invasion, tumor site and operation type, postoperative chemotherapy, and five-year overall survival were recorded and evaluated. In our study, 93 cases (42.5%) were signet ring cell carcinoma only, and 126 cases (57.5%) were signet ring cell carcinoma coexisting with other components (such as adenocarcinoma or mucus adenocarcinoma). Eighty-three patients were female, 136 were male, 46 occurred at the gastroesophageal junction (21.0%), 63 at the fundus/body (28.8%), 80 were antrum/pylorus (36.5%), and 30 were whole stomach (13.7%). The prognosis of gastric antrum/ pylorus cancer was the best (P < 0.05). There were 133 patients (60.7%) with stage III, and the single factor analysis showed that the earlier the stage, the better the prognosis. The overall five-year survival rate was 30.1% in all patients. One-hundred and 41 patients (64.4%) received D2 radical surgery, 64 (29.2%) received D1 radical operation, and 14 (6.4%) received palliative resection, and the patients who received D2 had the best overall survival (P < 0.05). The survival time of the paclitaxel-based regimen in postoperative adjuvant chemotherapy tended to be prolonged. There was no statistical difference in overall survival between the percentage of signet-ring cells and sex. In summary, age, tumor stage, and surgical resection combined with D2 lymphadenectomy were independent prognostic factors for SRC. Adjuvant chemotherapy with a paclitaxel-based regimen may improve the survival of patients with SRC.
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http://dx.doi.org/10.1177/1533033820983812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780316PMC
December 2020

Fat-Water Swaps in Iterative Decomposition of Water and Fat With Echo Asymmetry and Least-Squares Estimation Magnetic Resonance Imaging for Postinstrumentation Spine.

J Comput Assist Tomogr 2020 Nov/Dec;44(6):977-983

Objective: To determine the frequencies of fat-water swaps in iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) water-only images of the postinstrumentation spine and discuss the efficiency of in-phase imaging in improving visibility of the thecal sac.

Materials And Methods: A total of 276 patients (167 women; mean age, 62.3 years; range, 23-89 years) with metallic devices on the lumbar spine who received complete routine 1.5 T MR imaging, including axial and sagittal images of T1-weighted, T2-weighted, and T2-weighted IDEAL sequences, were included. The exclusion criteria were significant motion artifacts and severe metallic artifacts in any one of the sequences. The images were reviewed by two radiologists to identify fat-water swaps that were divided into 3 groups: extraspinal swaps, intraspinal swaps in sagittal images, and intraspinal swaps in axial images. The qualitative evaluations for the spinal canal in axial images were performed by rating on a five-point scale. Side-by-side comparisons of T2-weighted images and IDEAL in-phase images were also performed.

Results: In patient-based data of 276 patients, extraspinal fat-water swaps were noted in 10 patients (3.6%) and intraspinal swaps were noted in 160 patients (58.0%). The intraspinal swaps had a higher incidence in the patients with more levels of metallic devices with screws and the trend was not noted in the extraspinal swaps. A total of 928 axial levels were evaluated in the level-based data of axial images. T1-weighted, T2-weighted, and IDEAL in-phase images had significantly better imaging quality than the IDEAL water-only images (3.9 ± 0.4, 3.9 ± 0.3, 3.8 ± 0.4 vs 3.0 ± 1.3, all P < 0.001). Compared with T2-weighted images, most of the IDEAL in-phase images (reader 1, 90.9%; reader 2, 86.7%) present similar quality.

Conclusion: Iterative decomposition of water and fat with echo asymmetry and least-squares estimation sequence can provide good fat suppression in most spine MRI with metallic devices but the loss of cerebrospinal fluid signal intensities due to fat-water swaps are noted in more than half of postinstrumentation spine. Routine reconstruction of in-phase images is recommended to improve evaluation of the thecal sac by avoiding pitfall caused by fat-water swaps.
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http://dx.doi.org/10.1097/RCT.0000000000001092DOI Listing
December 2020

Real-World Study of Adding Bevacizumab to Chemotherapy for Ovarian, Tubal, and Peritoneal Cancer as Front-Line or Relapse Therapy (ROBOT): 8-Year Experience.

Front Oncol 2020 14;10:1095. Epub 2020 Jul 14.

Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

This study aimed to determine the real-world, long-term prognostic impacts, and adverse effects (AEs) of bevacizumab (BEV) in Asian patients with ovarian/tubal/peritoneal cancers. We retrospectively reviewed the medical records of consecutive patients with ovarian/tubal/peritoneal cancer on front-line chemotherapy with or without BEV (Cohort 1) and those who relapsed following chemotherapy and/or BEV (Cohort 2) between 2011 and 2018 in a tertiary medical centre. Patient characteristics, BEV dosages, clinical outcomes, and AEs were analyzed. Hazard ratios for disease progression and death were analyzed using a cox proportional regression model. Benefits of BEV used throughout triweekly, in terms of improved progression-free survival (PFS) and overall survival (OS), were observed at a dosage of 7.5-15 mg/kg among advanced-stage Cohort 1 patients. A progression-free interval of <6 months was the strongest predictor of disease progression and death in advanced-stage patients. BEV throughout and optimal cytoreduction were independent predictors of reduced disease progression. No prognostic advantage was observed between serous and clear cell histologies when BEV was added. Moreover, BEV resulted in improved OS in Cohort 2 patients, especially in the platinum-sensitive subgroup. Most patients had a front-line BEV dosage <10 mg/kg per cycle with <10 treatment cycles. Low rates and grades of BEV-related AEs were observed in both cohorts. BEV used throughout effectively extended PFS and OS in advanced-stage patients with ovarian/tubal/peritoneal cancer. Patients with platinum-sensitive carcinoma, treated with BEV, had a significant improvement in OS and extended PFS. Therefore, BEV can safely be added to chemotherapy for ovarian/tubal/peritoneal cancers.
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http://dx.doi.org/10.3389/fonc.2020.01095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372289PMC
July 2020

Herbal complex '' improves motor endplate function of denervated-dependent skeletal muscle atrophy in rat.

J Integr Neurosci 2020 Mar;19(1):89-99

Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, P. R. China.

Denervated-dependent skeletal muscle atrophy is a disease induced by skeletal muscle associated peripheral neuro-disconnection. Its specific molecular mechanisms remain unknown. The treating for denervated-dependent skeletal muscle atrophy is applied with an herbal complex Buyang Huanwu Tang used in traditional Chinese medicine and subjected to the established denervated-dependent skeletal muscle atrophy in rat models, and the therapeutic effects and associated mechanisms were evaluated in the pathogenesis of denervated-dependent skeletal muscle atrophy. Denervated-dependent skeletal muscle atrophy in rats was established and randomly divided into eight groups, including Normal control, Model, Positive control, Model + Buyang Huanwu Tang, Model + astragalus extracts, Model + Buyang Huanwu Tang-astragalus, Buyang Huanwu Tang + LY294002, and astragalus extract + LY294002 group. Hematoxylin-eosin staining and quantitative RT-PCR (qRT-PCR) assay were used to examine the inflammatory response of muscle tissues. Quantitative RT-PCR and Western blotting assay were utilized to analyze mRNA and protein expression. Immunohistochemistry assay was used to detect molecule expression in anterior cervical muscle tissues. Motor endplate activity was examined using the wholemount acetylcholinesterase staining method. The wet mass ratio of anterior cervical muscle was measured. The results indicated that Buyang Huanwu Tang treatment significantly alleviated inflammatory response, enhanced acetylcholinesterase activity, and motor endplate functions, and promoted wet mass of anterior cervical muscle compared to denervated-dependent skeletal muscle atrophy rat models ( < 0.05). Buyang Huanwu Tang regulated molecules of PI3K/PKB/GSK3β/FOXO1 signaling pathway. Buyang Huanwu Tang significantly reduced muscle atrophy F-box protein, MuFR-1, Bax and caspase 9 expression, significantly enhanced Bcl-2 expression, and remarkably increased element-binding protein and vascular endothelial growth factor levels, compared to Model group ( < 0.05). Buyang Huanwu Tang suppressed caspase 9 and caspase 3 activity and associated apoptosis. Moreover, PI3K specific blocker, LY294002, significantly inhibited the effects of Buyang Huanwu Tang on the above molecule expression ( < 0.05). In conclusion, Buyang Huanwu Tang improved motor endplate functions of denervated-dependent skeletal muscle atrophy rat model through suppressing mitochondria-mediated apoptosis and activating PI3K/PKB/FOXO1 signaling pathway.
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http://dx.doi.org/10.31083/j.jin.2020.01.1226DOI Listing
March 2020

Comparing PI3K/Akt Inhibitors Used in Ovarian Cancer Treatment.

Front Pharmacol 2020 3;11:206. Epub 2020 Mar 3.

Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Epithelial ovarian carcinoma (EOC) is the most lethal gynecological malignancy. Herein, we sought to determine the efficacy of phosphoinositide 3-kinase (PI3K)/Akt inhibition using three AZD compounds in a NOD-SCID xenograft mouse model and Akt regulation in a panel of eight ovarian cancer cell lines. Elevated Akt phosphorylation on Ser473 but not on Thr308 in cancerous tissues correlated with short progression-free survival (PFS), overall survival (OS), and death. AZD8835 and AZD8186 inhibited Akt phosphorylation while AZD5363 augmented its phosphorylation on Ser473. To add, all compounds inhibited the Akt downstream effectors 4E-BP1 and p70S6 kinase. AZD8835 and AZD5363 sensitized chemoresistant ovarian cancer cells to cisplatin and paclitaxel treatment. Only AZD5363 could inhibit COL11A1 mRNA and promoter activity, which are important factors in Akt regulation and chemoresistance in ovarian cancer. By using a mouse xenograft model, AZD8835 and AZD5363, but not AZD8186, caused a significant reduction in tumor formation. AZD compounds did not change the mRNA expression of BRCA1/BRCA in ovarian cancer cells, but AZD8835 inhibited BRCA1/BRCA2 mRNA expression and p-ERK protein expression in OVCAR-8 cells with the mutation. This study highlights the importance of PI3K/Akt in ovarian tumor progression and chemoresistance and the potential application of AZD compounds, especially AZD8835 and AZD5363, as therapeutic agents for the treatment of ovarian cancer.
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http://dx.doi.org/10.3389/fphar.2020.00206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063971PMC
March 2020

Estrogen Receptor, Inflammatory, and FOXO Transcription Factors Regulate Expression of Myasthenia Gravis-Associated Circulating microRNAs.

Front Immunol 2020 21;11:151. Epub 2020 Feb 21.

Department of Neuroscience, Clinical Neurophysiology, Uppsala University, Uppsala, Sweden.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate important intracellular biological processes. In myasthenia gravis (MG), a disease-specific pattern of elevated circulating miRNAs has been found, and proposed as potential biomarkers. These elevated miRNAs include miR-150-5p, miR-21-5p, and miR-30e-5p in acetylcholine receptor antibody seropositive (AChR+) MG and miR-151a-3p, miR-423-5p, let-7a-5p, and let-7f-5p in muscle-specific tyrosine kinase antibody seropositive (MuSK+) MG. In this study, we examined the regulation of each of these miRNAs using chromatin immunoprecipitation sequencing (ChIP-seq) data from the Encyclopedia of DNA Elements (ENCODE) to gain insight into the transcription factor pathways that drive their expression in MG. Our aim was to look at the transcription factors that regulate miRNAs and then validate some of those with cell lines that have sufficient expression of these transcription factors This analysis revealed several transcription factor families that regulate MG-specific miRNAs including the Forkhead box or the FOXO proteins (FoxA1, FoxA2, FoxM1, FoxP2), AP-1, interferon regulatory factors (IRF1, IRF3, IRF4), and signal transducer and activator of transcription proteins (Stat1, Stat3, Stat5a). We also found binding sites for nuclear factor of activated T-cells (NFATC1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), early growth response factor (EGR1), and the estrogen receptor 1 (ESR1). AChR+ MG miRNAs showed a stronger overall regulation by the FOXO transcription factors, and of this group, miR-21-5p, let-7a, and let 7f were found to possess ESR1 binding sites. Using a murine macrophage cell line, we found activation of NF-κB -mediated inflammation by LPS induced expression of miR-21-5p, miR-30e-5p, miR-423-5p, let-7a, and let-7f. Pre-treatment of cells with the anti-inflammatory drugs prednisone or deflazacort attenuated induction of inflammation-induced miRNAs. Interestingly, the activation of inflammation induced packaging of the AChR+-specific miRNAs miR-21-5p and miR-30e-5p into exosomes, suggesting a possible mechanism for the elevation of these miRNAs in MG patient serum. In conclusion, our study summarizes the regulatory transcription factors that drive expression of AChR+ and MuSK+ MG-associated miRNAs. Our findings of elevated miR-21-5p and miR-30e-5p expression in immune cells upon inflammatory stimulation and the suppressive effect of corticosteroids strengthens the putative role of these miRNAs in the MG autoimmune response.
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http://dx.doi.org/10.3389/fimmu.2020.00151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046803PMC
March 2021

Repeated intravitreal injections of antivascular endothelial growth factor in patients with neovascular age-related macular degeneration may increase the risk of ischemic optic neuropathy.

BMC Ophthalmol 2019 Dec 30;19(1):268. Epub 2019 Dec 30.

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

Background: Previous case reports have demonstrated the occurrence of ischemic optic neuropathy (ION) following intravitreal injections of antivascular endothelial growth factor (anti-VEGF). However, no previous studies have investigated the impact of injection numbers on the risk of ION. The aim of our study was to investigate whether repeated intravitreal injections of anti-VEGF would increase the risk of subsequent ION in patients with neovascular age-related macular degeneration (AMD).

Methods: A population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from 2007 to 2013. Neovascular AMD patients receiving intravitreal injections of anti-VEGF during the study period were enrolled in the study cohort. Enrollees were divided into three groups according to the categorized levels of injection number (first level: < 10 times, second level: 10-15 times, and third level: > 15 times). Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent ION among the three groups. Cox regression analyses were used to estimate crude and adjusted hazard ratios (HRs) for ION development with respect to the different levels of injection numbers. The confounders included for adjustment were age, sex, and comorbidities (diabetes, hypertension, hyperlipidemia, ischemic heart disease, and glaucoma).

Results: In total, the study cohort included 77,210 patients. Of these, 26,520, 38,010, and 12,680 were in the first-, second-, and third-level groups, respectively. The Kaplan-Meier method revealed that the cumulative hazards of ION were significantly higher in those who had a higher injection number. After adjusting for confounders, the adjusted HRs for ION in the second- and third-level groups were 1.91 (95% confidence interval [CI], 1.32-2.76) and 2.20 (95% CI, 1.42-3.43), respectively, compared with those in the first-level group.

Conclusions: Among patients with neovascular AMD, those who receive a higher number of anti-VEGF injections have a significantly higher risk of developing ION compared with individuals who receive a lower number of injections.
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http://dx.doi.org/10.1186/s12886-019-1284-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937927PMC
December 2019

(Dryopteridaceae), a new species from Taiwan.

PhytoKeys 2019 5;131:69-81. Epub 2019 Sep 5.

Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan National Sun Yat-sen University Kaohsiung Taiwan.

A new species of , , was found in central Taiwan. It most resembles B. virens var. compacta and . A phylogenetic tree of Taiwanese and other Asian species of species supports the recognition of the new species. Morphologically, the combination of anastomosing venation and fewer sterile pinnae are critical characters to discriminate from other Taiwanese species. can be further distinguished from B. virens var. compacta and by having lanceolate sterile pinnae and absent or fewer free veinlets in small areoles of sterile pinnae. The morphological descriptions, illustration, ecology and distribution of the new species are presented. A key to all Taiwanese is also provided.
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http://dx.doi.org/10.3897/phytokeys.131.36548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742672PMC
September 2019

The sex-specific association between maternal paraben exposure and size at birth.

Int J Hyg Environ Health 2019 07 25;222(6):955-964. Epub 2019 Jun 25.

Institute of Environmental and Occupational Health Sciences, School of Medicine, National Yang Ming University, Taipei, Taiwan. Electronic address:

Parabens are a group of esters of parahydroxybenzoic acid and are utilized as antimicrobial preservatives in the majority of personal care products (PCPs). Epidemiological studies regarding the adverse effects of parabens on fetuses are still limited. The aim of this study was to determine the association between maternal paraben exposure and birth outcomes. One hundred and ninety-nine pregnant women were enrolled, and maternal urine was collected in the third trimester. The urine concentrations of four parabens (methyl (MP), ethyl (EP), propyl (PP), and butyl (BP)) were determined by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Generalized additive model-penalized regression splines and a multivariable regression model were employed to determine the association between paraben exposure levels and birth outcomes. A causal mediation analysis was conducted to determine the mediation effect of oxidative stress on birth outcomes. The geometric means of urinary MP, EP, PP, and BP were 51.79, 1.26, 4.21, and 1.25 μg/g cre., respectively. In the penalized regression splines, sex-specific associations between maternal MP levels and birth outcomes were observed; a downward curvature was observed between the MP level and birth weight, length, head circumference, and thoracic circumference among female newborns. Pregnant women in the group with MP levels above the third quartile had neonates with significantly lower body weight (β = -215.98 g, p value = 0.02) compared to those in the group with MP levels lower than the third quartile. No significant mediation of oxidative stress was observed between maternal MP exposure and female birth weight. The estimated proportion mediated ranged from -6% to 15%. The negative association between maternal paraben exposure and female birth outcomes in relation to child development should be carefully considered.
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http://dx.doi.org/10.1016/j.ijheh.2019.06.004DOI Listing
July 2019

Buyang Huanwu Tang alleviates inflammation and improves motor endplate functions in DSMA rat models by activating several biological molecules and associated signaling pathways.

Am J Transl Res 2019 15;11(5):3056-3068. Epub 2019 May 15.

Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School Nanjing, China.

Denervated-dependent skeletal muscle atrophy (DSMA) is considered to be the neuro-disconnection of skeletal muscle. This study aimed to investigate the protective effects of Buyang Huanwu Tang (BYHWT) on the DSMA and clarify associated molecular and genetic mechanisms. DSMA rat models were established according to the previously published study and divided into Model group and BYHWT group. Meanwhile, normal rats were assigned as Normal control (NC) group. Hematoxylin and eosin (HE) staining was used to examine inflammatory responses. Motor endplate activity was evaluated with wholemount acetylcholinesterase (AChE) staining. Mass-spectrometry analysis was conducted to compare differentially expressed proteins. RNAs were prepared and applied to gene functional analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze biological functions. The results indicated that BYHWT remarkably alleviated inflammatory responses and significantly improved motor endplate function, compared to that in DSMA Model rats (<0.05). In BYHWT group, there were 393 differentially up-regulated and 576 differentially down-regulated molecules compared to that in Model group. Comparing to Model group, the cellular response to interferon-gamma, integral component of plasma membrane and voltage-gated potassium channel activity genes in BYHWT group were the most biological process (BP), cellular component (CC) and molecular function (MF) differential genes, respectively. Fructose/mannose metabolism and glycerolipid metabolism KEGG signaling pathways illustrated the most significant enrichment of differentially expressed genes. In conclusion, BYHWT alleviated the inflammations and improved the motor endplate function of DSMA rats by activating cellular response to interferon-gamma, integral component of plasma membrane and voltage-gated potassium channel activity genes and associated signaling pathways.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556633PMC
May 2019

A Dose Escalation Study of Trientine Plus Carboplatin and Pegylated Liposomal Doxorubicin in Women With a First Relapse of Epithelial Ovarian, Tubal, and Peritoneal Cancer Within 12 Months After Platinum-Based Chemotherapy.

Front Oncol 2019 24;9:437. Epub 2019 May 24.

Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer-related deaths worldwide. Preclinical studies found that copper-lowering agents could re-sensitize platinum-resistant cancer cells by enhancing the human copper transporter 1 (hCtr1)-mediated uptake of platinum. In the clinic, re-sensitization of platinum-resistance in relapsed EOC has been discovered by the application of trientine plus platinum (NCT01178112). However, no pharmacokinetic data of trientine has been reported in cancer patients. Our study aimed to explore the safety and activity of trientine combined with carboplatin and pegylated liposomal doxorubicin (PLD) in patients with EOC, tubal, and peritoneal cancer who experienced disease progression during platinum-based chemotherapy or showed relapse <12 months after completing first-line chemotherapy. Also, we aimed to demonstrate pharmacokinetic parameters and to discover potential biomarkers in our EOC patients. In this dose escalation study, 18 Asian patients in six dosing cohorts received fixed doses of carboplatin (AUC 4) and PLD (LipoDox®, TTY Biopharm Co. Ltd., Taipei, Taiwan) (40 mg/m, day 1 per 4-week cycle), and escalated daily trientine doses (range: 300-1800 mg; initiated 7 days before the 1st combination cycle) according to a 3 + 3 design. No dose-limiting toxicity or treatment-related death was observed. Four patients (22.2%) developed grade 3 drug-related adverse events (AEs), whereas no grade 4 AEs were encountered. Anemia and grade 2 dizziness were the most common hematological toxicity and neurotoxicity, respectively. In a pharmacokinetics comparison with healthy volunteers in the literature, our patients achieved greater absorption after oral trientinem, and more rapid elimination of triethylenetetramine dihydrochloride at high doses. The clinical benefit rate was 33.3 and 50.0% in the platinum-resistant and the partially platinum-sensitive group, respectively. A high baseline serum iron level and low serum copper level might help differentiate subgroups of patients with different clinical responses. Nevertheless, no associations of the clinical response with the levels of serum hCtr1, ceruloplasmin, or copper were observed. Combination therapy with carboplatin, trientine, and PLD was well-tolerated and safe. Our results encourage the development of a future phase II trial. ClinicalTrials.gov # NCT03480750.
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http://dx.doi.org/10.3389/fonc.2019.00437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544081PMC
May 2019

Akt inhibitor SC66 promotes cell sensitivity to cisplatin in chemoresistant ovarian cancer cells through inhibition of COL11A1 expression.

Cell Death Dis 2019 04 11;10(4):322. Epub 2019 Apr 11.

Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

We studied Akt inhibition using SC66 in a NOD-SCID xenograft mouse model and a panel of eight ovarian cancer cell lines. Elevated phospho-Akt levels in cancerous tissue were associated with short progression-free survival and overall survival. Cell sensitivity to SC66 was inversely correlated with phospho-Akt and COL11A1 expression levels, as well as resistance to cisplatin or paclitaxel. SC66 inhibited phosphorylation of Akt and its downstream effectors 4EBP1 and p70S6 kinase. SC66 also attenuated expression of TWIST1 and Mcl-1, factors important in cell invasiveness and anti-apoptosis, respectively. SC66-sensitized chemoresistant cells to cisplatin and paclitaxel treatment, and promoted apoptosis. In addition, SC66 inhibited COL11A1 expression via decreased binding of CCAAT/enhancer-binding protein beta (c/EBPβ), reducing chemoresistance and decreasing binding of nuclear transcription factor Y (NF-YA) to COL11A1. A mouse xenograft experiment demonstrated that SC66 treatment caused a reduction in tumor formation and enhanced the therapeutic efficacy of cisplatin. This study demonstrates the role of Akt in ovarian tumor progression and chemoresistance, and supports the application of SC66 as a therapy for ovarian cancer.
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http://dx.doi.org/10.1038/s41419-019-1555-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459878PMC
April 2019

Associations between prenatal exposure to bisphenol a and neonatal outcomes in a Taiwanese cohort study: Mediated through oxidative stress?

Chemosphere 2019 Jul 15;226:290-297. Epub 2019 Mar 15.

Institute of Environmental and Occupational Health Sciences, School of Medicine, National Yang Ming University, Taipei, Taiwan. Electronic address:

This study determined whether maternal bisphenol A (BPA) exposure influences birth outcomes through oxidative stress and estimated the daily intake of BPA through breast milk for infants. One hundred and eighty-six pregnant women without pregnancy complications were enrolled and maternal urine was collected in the third trimester. Postnatal breast milk was collected in the first and third months after delivery. Concentrations of BPA were determined through ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Generalized additive model-penalized regression splines and a multivariable regression model were employed to determine the effects of BPA exposure and oxidative stress levels on birth outcomes. A causal mediation analysis was conducted to clarify the mediation effects of oxidative stress due to maternal BPA exposure on birth outcomes. The daily intake of BPA in breast milk was calculated using probabilistic risk assessment methods. The geometric means (geometric standard deviation) of BPA levels for maternal urine and first- and third-month breast milk were 2.19 (2.88) μg/g creatinine., 1.35 (3.53) ng/g, and 3.17 (2.97) ng/g, respectively. No significant mediation existed among maternal BPA exposure, oxidative stress level, and neonatal head circumference. Three percent of 1-monthold babies and 1% of 3-month-old babies exceeded the BPA tolerable daily intake of 4 μg/kg-bw/day proposed by the European Food Safety Authority. This study revealed the BPA exposure profile for pregnant women and infants in northern Taiwan. The marginally significant correlation between maternal BPA exposure and neonatal head circumference should be considered.
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http://dx.doi.org/10.1016/j.chemosphere.2019.03.093DOI Listing
July 2019

Red/green/blue LD mixed white-light communication at 6500K with divergent diffuser optimization.

Opt Express 2018 Sep;26(18):23397-23410

Enabling laser white-lighting at a correlated color temperature (CCT) of 6500K with the use of only red/green/blue (RGB) tri-color laser diodes (LDs) is demonstrated, which can further perform wavelength division multiplexing (WDM) communication with a high-spectral-usage 16 QAM-OFDM data stream at 11.2 Gbps over 0.5 m. The sampling rate of encoded data is optimized to avoid the aliasing effect and to effectively amplify the signal with high on/off extinction and modulation depth. Proper oversampling can decrease the peak-to-average power ratio (PAPR) of the OFDM data and filter out unwanted noise. There are also six different diffusers used to diverge the white-light mixed by the RGB LD beam. By analyzing the color-casting transmittance, surface roughness, CCT uniformity, divergent angle of the diffuser, and the data transmission capacity, the frosted glass (FG) diffuser with high transmittance diverges the white light with the divergent angle of ± 20° and supports the highest data rate of 14 Gbps over 0.5 m. To fit the day-light CCT, the blue LD power at an optimized bias current is further attenuated with a 0.6-optical density filter for reducing CCT from 100000K to 6500K; however, such an adjustment also degrades the SNR ratio to sacrifice the achievable data rate of the blue LD. The polycarbonate (PC) diffuser with proper surface roughness diverged white-light exhibits the best CCT uniformity and a divergent angle of ± 30° but supports a data rate of only 6.4 Gbps over 0.5 m. The poly (methyl methacrylate) PMMA diffuser scatters the white light with the largest angle of ± 40°; however, the data rate also decreases to 4.8 Gbps over 0.5 m.
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http://dx.doi.org/10.1364/OE.26.023397DOI Listing
September 2018

Interactive effects of nonylphenol and bisphenol A exposure with oxidative stress on fetal reproductive indices.

Environ Res 2018 11 7;167:567-574. Epub 2018 Aug 7.

Institute of Environmental and Occupational Health Sciences, National Yang Ming University, Taipei, Taiwan. Electronic address:

Nonylphenol (NP) and/or bisphenol A (BPA) may have reproductive effects. Although the mechanisms of action remain unclear, steroid hormones biosynthesis, hypothalamus pituitary adrenal axis activity, oxidative stress, and crosstalk interaction of NP and BPA mixture and its pathways may play a contributory role. This cross-sectional study examined whether the interactive effects of NP/BPA and oxidative stress biomarkers played a role in reproductive indices (penis length and anogenital distance (AGD)) in 244 mother-fetus pairs. Four biomarkers of oxidative stress, (8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NOGua), 8-iso-prostaglandin F (8-isoPF), and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) were simultaneously analyzed using the high-performance liquid chromatography-electrospray ionization tandem mass spectrometry method. No significant associations were found between reproductive indices and NP/BPA or oxidative stress biomarkers. Maternal exposure to a mixture of NP and BPA may enhance 8-OHdG. Interactive effects were found in the high 8-isoPF group, and prenatal NP exposure was inversely associated with penis length (β = -3.68 mm; p = 0.01). Similar results were noted among boys who were born to mothers in the high 8-isoPF group, in which BPA was inversely associated with penis length (β = -4.43 mm; p = 0.005). Our findings suggest important implications for prenatal exposure to oxidative stress, as evidenced by the 8-isoPF2α level. Thus, NP and BPA may interact to shape fetal reproductive tract development, particularly in boys. The interactive effects of NP/BPA, oxidative stress, and reproductive indices should be considered.
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http://dx.doi.org/10.1016/j.envres.2018.08.007DOI Listing
November 2018

Sonographic median nerve change after steroid injection for carpal tunnel syndrome.

Muscle Nerve 2018 09;58(3):402-406

Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Beitou District, Taipei City, 11217, Taiwan.

Introduction: The sonographic changes of the median nerve after steroid injection for carpal tunnel syndrome (CTS) still require investigation.

Methods: Sixty-two patients with CTS were included. The Boston Carpal Tunnel Questionnaire was administered, and ultrasonographic examinations were performed before and at 2, 6, and 12 weeks after steroid injection. At 12 weeks, general improvement was scored on a 6-point Likert scale.

Results: After treatment, the cross-sectional area (CSA) of the median nerve was significantly reduced at 2-, 6-, and 12-week follow-ups (for each, P < 0.001, analysis of variance). The "significant improvement" group (n = 39) had a significantly greater reduction in the CSA at the carpal tunnel inlet (P = 0.014) and CSA in the proximal carpal tunnel (P = 0.003) compared with the "little/no improvement" group (n = 23).

Discussion: Sonographic measurement of CSA may be considered complementary to the standard clinical evaluation in monitoring of treatment response in patients with CTS. Muscle Nerve 58: 402-406, 2018.
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http://dx.doi.org/10.1002/mus.26171DOI Listing
September 2018

Simultaneous determination of nine neonicotinoids in human urine using isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry.

Environ Pollut 2018 Sep 15;240:647-652. Epub 2018 May 15.

Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, China. Electronic address:

Neonicotinoids (neonics), a class of systemic insecticides, have been frequently detected in pollen, vegetables, and fruits. Recently, an increasing concern has been aroused for human exposure to neonics. However, biological monitoring for quantifying body burden of neonics has rarely been reported. In this study, we developed an isotope-dilution ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method to simultaneously quantify nine neonics, including acetamiprid (ACE), thiamethoxam (THIAM), imidacloprid (IMIP), clothianidin (CLO), flonicamid (FLO), thiacloprid (THIAC), dinotefuran (DIN), nitenpyram (NIT), and imidaclothiz (IMIT) in urine. The limits of quantification were 0.1 μg/L for ACE, FLO, DIN, NIT and IMIT, and 0.2 μg/L for THIAM, IMIP, CLO, and THIAC. The overall recoveries were 80.8-103%, 81.5-91.7% and 83.0-92.3% for QA/QC samples fortifying at 1, 25, and 100 μg/L levels, respectively. UPLC/MS/MS method was used to analyze urine samples obtained from 10 children in Hangzhou, China. The detection frequencies were 80% for ACE and IMIP, 70% for THIAM and CLO, 20% for DIN and IMIT and 10% for THIAC. FLO and NIT were not detected in those urine samples. The data provided here will be helpful for conducting biological monitoring of neonics exposure in the future.
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http://dx.doi.org/10.1016/j.envpol.2018.04.144DOI Listing
September 2018

Paper-Based Microfluidic Platforms for Understanding the Role of Exosomes in the Pathogenesis of Major Blindness-Threatening Diseases.

Nanomaterials (Basel) 2018 May 8;8(5). Epub 2018 May 8.

Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan.

Emerging roles of exosomes in the pathogenesis of major blindness-threatening diseases, such as age-related macular degeneration, glaucoma, and corneal dystrophy, were discovered by aqueous humor analysis. A new diagnostic method using cellulose-based devices and microfluidic chip techniques for the isolation of exosomes from aqueous humor is less cumbersome and saves time. This method will enable more investigations for aqueous humor analysis in the future.
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http://dx.doi.org/10.3390/nano8050310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977324PMC
May 2018

Vitamin D-Binding Protein Enhances Epithelial Ovarian Cancer Progression by Regulating the Insulin-like Growth Factor-1/Akt Pathway and Vitamin D Receptor Transcription.

Clin Cancer Res 2018 07 23;24(13):3217-3228. Epub 2018 Feb 23.

Department of Obstetrics & Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Malignant ascites of epithelial ovarian cancer (EOC) helps identify prognostic biomarkers or mechanisms of tumor progression. Vitamin D-binding protein (DBP) was revealed to be upregulated in EOC ascites in our previous proteomic study. Here, we examined the role of DBP in EOC. We analyzed ascites, serum, and tissue samples of patients with newly diagnosed EOC to determine the prognostic effects of DBP. We verified DBP function using orthotopic animal models and DBP regulation in ovarian cancer cell lines. Elevated ascitic DBP was significantly associated with poor response to chemotherapy, short progression-free interval, increased cancer progression, and death. Ascitic DBP overexpression was an independent unfavorable biomarker for progression-free survival; DBP overexpression in cancerous tissue was significantly related to chemoresistance. and investigations demonstrated an important role for DBP in ovarian cancer progression. Orthotopic model mice inoculated with DBP knockdown ovarian cancer cells displayed a significant reduction in tumor formation, malignant cell number, ascitic DBP levels, invasiveness, and metastasis, and increased survival compared with controls. In presence of vitamin D receptor (VDR), DBP promoted cell aggression (invasion and doubling time) via activation of the insulin-like growth factor-1/insulin-like growth factor-binding protein-2/Akt axis, and induced suppression of vitamin D-responsive genes. A NF-κB p65-binding site in the promoter was identified as a major determinant of DBP-dependent promoter activation. This study highlights the importance of DBP in ovarian tumor progression and the potential application of DBP as a therapeutic target for EOC. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-2943DOI Listing
July 2018

Feasibility of using urinary N7-(2-carbamoyl-2-hydroxyethyl) Guanine as a biomarker for acrylamide exposed workers.

J Expo Sci Environ Epidemiol 2018 11 20;28(6):589-598. Epub 2018 Feb 20.

Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, Taipei City, Taiwan.

Acrylamide (AA), a probable human carcinogen, is a widely-used industrial chemical but is also present in tobacco smoke and carbohydrate-rich foods processed at high temperatures. AA is metabolized to glycidamide (GA) to cause the formation of DNA adducts. N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GAG), the most abundant DNA adduct induced by GA, was recently detected in urine of smokers and non-smokers. In this study, we assessed the variability of AA exposure and biomarkers of AA exposure in urine samples repeatedly collected from AA-exposed workers and explored the half-life of N7-GAG. A total of 8 AA-exposed workers and 36 non-exposed workers were recruited. Pre-shift and post-shift urine samples were collected from the exposed group in parallel with personal sampling for eight consecutive days and from the control group on day 1 of the study. Urinary N7-GAG and the mercapturic acids of AA and GA, namely N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-(R,S)-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) were analyzed using on-line solid phase extraction-liquid chromatography-electrospray ionization/tandem mass spectrometry methods. We found that N7-GAG levels in urine were significantly higher in exposed workers than in controls and that N7-GAG level correlated positively with AAMA and GAMA levels. Results from this study showed that AAMA and GAMA possibly remain the more preferred biomarkers of AA exposure and that N7-GAG levels could be elevated by occupational exposures to AA and serve as a biomarker of AA-induced genotoxicity for epidemiological studies.
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http://dx.doi.org/10.1038/s41370-018-0018-0DOI Listing
November 2018

Hypermethylation of contributes to cell proliferation and is a prognostic marker of colorectal cancer.

Oncotarget 2017 Dec 1;8(69):113431-113443. Epub 2017 Nov 1.

Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli, Taiwan.

Aberrant hypermethylation of CpG islands in tumor suppressor genes (TSGs) contributes to colorectal tumorigenesis. To identify new colorectal cancer (CRC) screening marker, we investigated DNA methylation alterations in novel TSGs. Using HumanMethylation450 BeadChip arrays, CpG regions in were the most highly methylated among all genomic regions in 26 colorectal tumors compared to paired non-neoplastic tissues from a Taiwan cohort. Therefore, was selected for further analysis. Quantitative methylation-specific real-time PCR revealed that 86.7% (117/135) of CRC patients exhibited hypermethylated . Real-time reverse transcription PCR identified that BEND5 mRNA expression was downregulated in 68% (32/47) of the analyzed samples. hypermethylation was associated with poor overall survival (OS) in Taiwan patients with early-stage CRC ( 0.037). In a CRC tissue set from South Korea, OS was higher in patients with high BEND5 protein expression than in those with low BEND5 protein expression ( 0.037) by using immunohistochemistry assays. Consistently, BEND5 hypermethylation was associated with poor OS in patients with early-stage CRC in The Cancer Genome Atlas (TCGA) data set ( 0.003). Multivariate Cox proportional hazards regression analysis further supported that hypermethylation of BEND5 genes was significantly associated with OS in Taiwan and TCGA CRC patients ( 0.023 and 0.033, respectively). Finally, the cell model assay with transient transfection of BEND5 or si-BEND5 knockdown indicated that BEND5 inhibited cancer cell proliferation. In conclusion, epigenetic alteration in the candidate TSG contributes to colorectal cancer development and is a prognostic marker of CRC.
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http://dx.doi.org/10.18632/oncotarget.22266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768337PMC
December 2017

Endoscope-assisted vitrectomy in the management of retinal detachment with corneal opacity.

Taiwan J Ophthalmol 2017 Jul-Sep;7(3):164-167

Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan.

A 51-year-old male who had suffered from right eye rhegmatogenous retinal detachment with proliferative vitreoretinopathy received surgical treatments which included the following procedures: lens extraction, scleral buckle, vitrectomy, membrane peeling, photocoagulation, and silicone oil injection. The presenting visual acuity of the right eye was light perception. Slit-lamp examination revealed corneal opacity without a visible fundus. B-scan ultrasonography revealed retinal detachment. Endoscope-assisted vitrectomy was then performed in December 2014. The procedure also included photocoagulation and silicone oil tamponade. Postoperative follow-up confirmed retinal attachment through B-scan ultrasonography. To assess the feasibility of a penetrating keratoplasty, an endoscopic evaluation was performed in May 2015. A temporal retinal break was noted, and photocoagulation was applied around the break as well as the peripheral retina. Endoscopy later confirmed the retinal attachment. From the present case, we concluded that endoscope-assisted vitrectomy could be an option for patients with corneal opacity indicated for vitreoretinal surgery. We report the first case of endoscope-assisted vitrectomy in the management of retinal detachment in Taiwan.
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http://dx.doi.org/10.4103/tjo.tjo_25_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637383PMC
October 2017

[Relationship between seedling grade of Codonopsis pilosula and yield and quality of medicinal materials].

Zhongguo Zhong Yao Za Zhi 2016 Nov;41(21):3950-3955

Key Laboratory of Traditional Chinese Medicine Quality and Standard of Gansu Province, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China.

The study is aimed to research the relationship between the seedling grade of Codonopsis pilosula and yield and quality of medicinal materials, so as to provide basis for establishing seedling standard. Thirty seedlings of C. pilosula were collected from the main production areas in Gansu province, such as Weiyuan, Minxian, Zhangxian, Dangchang and Longxi, root length and diameter and weight of all the samples were measured. According to the clustering results, seedlings were divided into 3 levels, and field experiments were conducted with three levels seedling, yield and quality were tested in laboratory. Results have showed that emergence of grades 1 was faster than that of grades 2 and 3. Yield of grades 1 was significantly higher than that of grades 2 and 3 (P<0.05). Propargyl glycoside content of grades 1 was the highest, and significantly higher than that of grades 3. Polysaccharide content of grades 3 was the highest and significantly higher than that of grades 1 and 2 (P<0.05). So considering yield, quality and investment cost of C. pilosula, planting seedlings of C. pilosula should select that root length>15.6 cm, root diameter>2.7 mm, root weight>0.56 g.
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http://dx.doi.org/10.4268/cjcmm20162111DOI Listing
November 2016

Violet Laser Diode Enables Lighting Communication.

Sci Rep 2017 09 5;7(1):10469. Epub 2017 Sep 5.

Graduate Institute of Photonics and Optoelectronics, National Taiwan University (NTU), No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan, R.O.C..

Violet laser diode (VLD) based white-light source with high color rendering index (CRI) for lighting communication is implemented by covering with YAlO:Ce (YAG:Ce) or LuAlO:Ce/CaAlSiN:Eu (LuAG:Ce/CASN:Eu) phosphorous diffuser plates. After passing the beam of VLD biased at 70 mA (~2I ) through the YAG:Ce phosphorous diffuser, a daylight with a correlated color temperature (CCT) of 5068 K and a CRI of 65 is acquired to provide a forward error correction (FEC) certified data rate of 4.4 Gbit/s. By using the VLD biased at 122 mA (~3.5I ) to excite the LuAG:Ce/CASN:Eu phosphorous diffuser with 0.85-mm thickness, a warm white-light source with a CCT of 2700 K and a CRI of 87.9 is obtained at a cost of decreasing transmission capacity to 2.4 Gbit/s. Thinning the phosphor thickness to 0.75 mm effectively reduces the required bias current by 32 mA to achieve the same CCT for the delivered white light, which offers an enlarged CRI of 89.1 and an increased data rate of 4.4 Gbit/s. Further enlarging the bias current to 105 mA remains the white-light transmission capacity at 4.4 Gbit/s but reveals an increased CCT of 3023 K and an upgraded CRI of 91.5.
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http://dx.doi.org/10.1038/s41598-017-11186-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585212PMC
September 2017

Blue Laser Diode Based Free-space Optical Data Transmission elevated to 18 Gbps over 16 m.

Sci Rep 2017 09 5;7(1):10478. Epub 2017 Sep 5.

Graduate Institute of Photonics and Optoelectronics, and the Department of Electrical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, R.O.C., Taiwan.

Up to 18-Gbps direct encoding of blue laser diode (BLD) is demonstrated for free-space data transmission. By reshaping the orthogonal frequency multiplexed (16-QAM OFDM) stream with sidelobe filtering, the raw data rate expedites from 17.2 to 18.4 Gbps. Employing an ultrafast p-i-n photodiode with smaller active area diameter and lower noise equivalent power significantly enlarges the data rate by 1.6 Gbps or upgrades the signal-to-noise ratio (SNR) by 0.2 dB. Replacing the 80-mW BLD with the 120-mW one essentially increases the received SNR by 0.4 dB under enhanced modulation throughput. Reinforcing the beam collimation and collection by increasing the numerical aperture with a plano-convex hyper-hemispherical lens further improves the SNR by 0.6 dB. After optimization, the 16-QAM OFDM data with and without sidelobe filtering are respectively delivered at raw data rates of 16.4 and 18 Gbps with spectral-density usage efficiency as high as 4 bit/s/Hz over 16 m in free space, wherein the BLD carried QAM-OFDM data stream remains its capacity after reformation with sidelobe filtering as the superior inter-carrier-interference immunity reinforces.
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http://dx.doi.org/10.1038/s41598-017-10289-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585402PMC
September 2017