Motivation Ovarian cancer (OC) is a highly lethal gynecological malignancy. Extensive research has shown that OC cells undergo significant metabolic alterations during tumorigenesis. In this study, ...we aim to leverage these metabolic changes as potential biomarkers for assessing ovarian cancer. Methods A functional module-based approach was utilized to identify key gene expression pathways that distinguish different stages of ovarian cancer (OC) within a tissue biopsy cohort. This cohort consisted of control samples (n = 79), stage I/II samples (n = 280), and stage III/IV samples (n = 1016). To further explore these altered molecular pathways, minimal spanning tree (MST) analysis was applied, leading to the formulation of metabolic biomarker hypotheses for OC liquid biopsy. To validate, a multiple reaction monitoring (MRM) based quantitative LCMS/MS method was developed. This method allowed for the precise quantification of targeted metabolite biomarkers using an OC blood cohort comprising control samples (n = 464), benign samples (n = 3), and OC samples (n = 13). Results Eleven functional modules were identified as significant differentiators (false discovery rate, FDR < 0.05) between normal and early-stage, or early-stage and late-stage ovarian cancer (OC) tumor tissues. MST analysis revealed that the metabolic L-arginine/nitric oxide (L-ARG/NO) pathway was reprogrammed, and the modules related to "DNA replication" and "DNA repair and recombination" served as anchor modules connecting the other nine modules. Based on this analysis, symmetric dimethylarginine (SDMA) and arginine were proposed as potential liquid biopsy biomarkers for OC assessment. Our quantitative LCMS/MS analysis on our OC blood cohort provided direct evidence supporting the use of the SDMA-to-arginine ratio as a liquid biopsy panel to distinguish between normal and OC samples, with an area under the ROC curve (AUC) of 98.3%. Conclusion Our comprehensive analysis of tissue genomics and blood quantitative LC/MSMS metabolic data shed light on the metabolic reprogramming underlying OC pathophysiology. These findings offer new insights into the potential diagnostic utility of the SDMA-to-arginine ratio for OC assessment. Further validation studies using adequately powered OC cohorts are warranted to fully establish the clinical effectiveness of this diagnostic test. Keywords: Arginase (ARG), Nitric oxide synthase (NOS), Dimethylarginine dimethylaminohydrolase (DDAH), Protein arginine methyltransferases (PRMT), Asymmetric dimethylarginine (ADMA), Symmetric dimethylarginine (SDMA), Dimethylamine (DMA), Metabolic reprogramming, Ovarian cancer (OC), L-arginine/nictric oxide (L-ARG/NO)
Background
Kawasaki disease (KD) is the leading cause of acquired heart disease in children. The major challenge in KD diagnosis is that it shares clinical signs with other childhood febrile control ...(FC) subjects. We sought to determine if our algorithmic approach applied to a Taiwan cohort.
Methods
A single center (Chang Gung Memorial Hospital in Taiwan) cohort of patients suspected with acute KD were prospectively enrolled by local KD specialists for KD analysis. Our previously single-center developed computer-based two-step algorithm was further tested by a five-center validation in US. This first blinded multi-center trial validated our approach, with sufficient sensitivity and positive predictive value, to identify most patients with KD diagnosed at centers across the US. This study involved 418 KDs and 259 FCs from the Chang Gung Memorial Hospital in Taiwan.
Findings
Our diagnostic algorithm retained sensitivity (379 of 418; 90.7%), specificity (223 of 259; 86.1%), PPV (379 of 409; 92.7%), and NPV (223 of 247; 90.3%) comparable to previous US 2016 single center and US 2020 fiver center results. Only 4.7% (15 of 418) of KD and 2.3% (6 of 259) of FC patients were identified as indeterminate. The algorithm identified 18 of 50 (36%) KD patients who presented 2 or 3 principal criteria. Of 418 KD patients, 157 were infants younger than one year and 89.2% (140 of 157) were classified correctly. Of the 44 patients with KD who had coronary artery abnormalities, our diagnostic algorithm correctly identified 43 (97.7%) including all patients with dilated coronary artery but one who found to resolve in 8 weeks.
Interpretation
This work demonstrates the applicability of our algorithmic approach and diagnostic portability in Taiwan.
Long-term antiplatelet agents including the potent P2Y12 antagonist ticagrelor are indicated in patients with a previous history of acute coronary syndrome. We sought to compare the effect of ...ticagrelor with that of aspirin monotherapy on vascular endothelial function in patients with prior acute coronary syndrome.
This was a prospective, single center, parallel group, investigator-blinded randomized controlled trial. We randomized 200 patients on long-term aspirin monotherapy with prior acute coronary syndrome in a 1:1 fashion to receive ticagrelor 60 mg BD (n=100) or aspirin 100 mg OD (n=100). The primary end point was change from baseline in brachial artery flow-mediated dilation at 12 weeks. Secondary end points were changes to platelet activation marker (CD41_62p) and endothelial progenitor cell (CD34/133) count measured by flow cytometry, plasma level of adenosine, IL-6 (interleukin-6) and EGF (epidermal growth factor), and multi-omics profiling at 12 weeks.
After 12 weeks, brachial flow-mediated dilation was significantly increased in the ticagrelor group compared with the aspirin group (ticagrelor: 3.48±3.48% versus aspirin: -1.26±2.85%, treatment effect 4.73 95% CI, 3.85-5.62,
<0.001). Nevertheless ticagrelor treatment for 12 weeks had no significant effect on platelet activation markers, circulating endothelial progenitor cell count or plasma level of adenosine, IL-6, and EGF (all
>0.05). Multi-omics pathway assessment revealed that changes in the metabolism and biosynthesis of amino acids (cysteine and methionine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis) and phospholipids (glycerophosphoethanolamines and glycerophosphoserines) were associated with improved brachial artery flow-mediated dilation in the ticagrelor group.
In patients with prior acute coronary syndrome, ticagrelor 60 mg BD monotherapy significantly improved brachial flow-mediated dilation compared with aspirin monotherapy and was associated with significant changes in metabolomic and lipidomic signatures.
URL: https://www.
gov; Unique identifier: NCT03881943.
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The enzyme β‐galactosidase catalyzes the hydrolysis of lactose into glucose and galactose. An extracellular β‐galactosidase of 489‐amino acid length and 57‐kDa molecular weight monomer ...was isolated, expressed and purified from an extreme thermophile,
Thermococcus kodakarensis
KOD1. Here, the enzyme kinetic parameters of the β‐Galactosidase were analyzed through the hydrolysis of the yellow chromogenic substrate, chlorophenol red β‐D‐galactopyranoside (CPRG). Ad, the red colored chlorophenol red product was measured. The optimum pH and optimum temperature for the enzyme activity were 6.5 and 100°C. The maximum enzyme activity was retained even at 110°C, the highest temperature used in the study. The kinetic parameters K
m
and V
max
of the purified enzyme were 1.4mM and 2.5 U/mg for CPRG at the optimum pH and temperature conditions. The enzyme could not be inhibited with glucosidase inhibitors.
The research was supported by the National Taipei University of Technology to KYH (NTUT 100‐140‐01, NTUT 99‐140‐04) and by Academia Sinica to YML.
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Alternation of glycan synthesis is an important process in cancer metastasis. And, the extent of poly‐N‐acetyllactosamine chains on tumor cells has been implicated for their metastatic ...potential. β1,3‐N‐acetylglucosamonyltransferase‐2 (β3GnT2) and β1,3‐N‐acetylglucosamonyltransferase‐8 (β3GnT8) are two of the glycosyltransferases responsible for the synthesis of poly‐N‐acetyllactosamine. Since Src is a well‐known oncogene, which has been implicated in pathways regulating cell proliferation, angiogenesis, invasion and metastasis, we had generated a stable mouse cell line expressing v‐Src. First, we had examined the expression of the two genes in stable transformed v‐Src and wild‐type NIH/3T3 cell lines. And, we found that the cell line with overexpressed Src had higher level β3GnT8 transcripts than the normal NIH/3T3 cell line. To further illustrate the regulatory role of Src on the two genes, we had investigated the expressions of β3GnT2 and β3GnT8 in SW620 and H23 by treating the cells with bosutinib, a Src inhibitor. We found that the decrease of the expression of β3GnT2 was not significant, but the expression of β3GnT8 was significantly decreased by the Src inhibitor. Furthermore, we had found that the surface expression of poly‐N‐acetyllactosamine was altered by the Src inhibitor, by FACS analysis.
This work is supported by the National Taipei University of Technology to KYH (NTUT 100‐140‐01, NTUT 99‐140‐04).
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The fast development of metal nanoparticles capped with organic monolayer is offering the possibility to create a whole new variety of products with novel characteristics, functions and ...applications. Among these, the nanoparticles covered with carbohydrates (glyconanoparticles) constitute a good bio‐mimetic model of carbohydrate presentation at the cell surface and are currently centered on many glycobiological and biomedical applications. In this paper, a series of novel D‐xylose gold nanoparticles with the linkers of alkyl or polyethylene glycol have been synthesized via D‐xylosethiols formed self‐assembled monolayers with gold nanoparticles (circa 5 nm diameter). D‐xylosethiols were characterized by FTIR, NMR. The characterizations of Xylose‐modified gold nanoparticles by TEM, UV‐Vis, FTIR and colorimetry techniques and bioassay are investigated.
This work is supported by the National Taipei University to SMC and KYH (NTUT 100‐140‐01, NTUT 99‐140‐04)
Cancer is one of the dreadful diseases taking many lives over the years. This disease can be diagnosed and cured but the reoccurrence of the disease is a common phenomenon as it is caused by genetic ...as well as environmental factors. Hence Precision Medicine, a personalized form of healthcare service can be the most effective treatment strategy for treating cancer, which includes individual genetics, environmental factors, and lifestyle data. Establishing a precision medicine platform integrating it with the data from the Next Generation Sequencing (NGS) will be one of the solutions for the researchers and clinicians in conducting their works. In this paper, we have designed workflows for genomics variants from data of the NGS and a platform for establishing a precision medicine database system which consists of information of genes responsible for various cancers and their corresponded drug information, which could serve the purpose of providing the best therapeutic modality for cancer treatment. Moreover, databases verified by the US Food and Drug Administration, an agency create a versatile and adaptable regulatory guideline for precision medicine with a focus on the data from the NGS. The main aim of these guidelines is to ensure patients to get precise, authentic and correct test results.
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YTCa, a novel human gene was first discovered in our studies for Dopa‐responsive dystonia by differential display. A unique cell model was established with the characteristic of the ...dominant‐negative effect of the GCH G201E mutation. By PCR‐based differential display, YTCa and other proteins were found to be involved in regulating cellular mRNA and protein half‐life. From bioinformatics analysis, we found that YTCa is located nearby chromosome 20q13. Although tissue distributions of YTCa mRNA were found in normal pancreas, muscle and heart, the protein can only be detected in brain by Western analysis. Moreover, normal tissue did not have detectable amounts of YTCa protein. In order to understand the functional role of YTCa, we have performed many experiments. First, overexpression of YTCa full‐length cDNA on NIH3T3 cell allowed cells to grow faster in tissue cultures under a low serum condition. Furthermore, nude mice injected with genetically altered NIH3T3 cells, stably transfected with YTCa formed tumors in 4 weeks.
Acknowledgement: This work is supported by the grant from Academia Sincia, Taiwan, ROC (No: AS‐94‐TP‐B17).
Differences in cultural and the convenience of obtaining information expose a significant difference in the effectiveness of learning between Indigenous and non-Indigenous students. Indigenous ...students frequently misunderstand the content and examples provided by the teachers, and cultural constraint is an important factor in learning. This study created a new learning system with information technology for Indigenous students. We established and integrated indigenous culture into a cloud-based Indigenous elementary school e-learning system. Students can read e- books online and study new vocabularies with teachers' explanations. Moreover, students can engage in exercises after completing very segment of a whole lesson. After finishing the course, students take an examination for evaluating the learning effects. All examples used in the e-books match the students' culture and lifestyle and can facilitate their understanding of the contents. We administered the test teaching course at 4 aboriginal elementary schools and found that the average score has improved significantly (p<;0.001) by 4 degrees(out of 40 in the Attitude of Health Posture) and shown that this e-learning system can enhance learning capability. In addition, we conducted a questionnaire to survey user satisfaction with this e-learning system, and the results show that most of the students (84.6%) were satisfied with the system.
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