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Biological evaluation of sulfonate and sulfate analogues of lithocholic acid: A bioisosterism-guided approach towards the discovery of potential sialyltransferase inhibitors for antimetastatic study

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Bioorganic & medicinal chemistry letters 2024年 105卷 129760页

作者： Ser John Lynon P Perez Chia-Ling Chen Tzu-Ting Chang Wen-Shan Li Institute of Chemistry Academia Sinica Taipei 115 Taiwan Department of Applied Chemistry National Yang Ming Chiao Tung University Hsinchu 300 Taiwan Sustainable Chemical Science and Technology Taiwan International Graduate Program Academia Sinica Taipei 115 Taiwan Biomedical Translation Research Center Academia Sinica Taipei 115 Taiwan. Institute of Chemistry Academia Sinica Taipei 115 Taiwan. Biomedical Translation Research Center Academia Sinica Taipei 115 Taiwan Department of Medicinal and Applied Chemistry College of Life Science Kaohsiung Medical University Kaohsiung 807 Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Doctoral Degree Program in Marine Biotechnology National Sun Yat-Sen University Kaohsiung 804 Taiwan Department of Chemistry College of Science Tamkang University New Taipei City 251 Taiwan. Electronic address: wenshan@gate.sinica.edu.tw.

The naturally occurring bile acid lithocholic acid (LCA) has been a crucial core structure for many non-sugar-containing sialyltranferase (ST) inhibitors documented in literature. With the aim of elucidating the impact of the terminal carboxyl acid substituent of LCA on its ST inhibition, in this present study, we report the (bio)isosteric replacement-based design and synthesis of sulfonate and sulfate analogues of LCA. Among these compounds, the sulfate analogue SPP-002 was found to selectively inhibit N-glycan sialylation by at least an order of magnitude, indicating a substantial improvement in both potency and selectivity when compared to the unmodified parent bile acid. Molecular docking analysis supported the stronger binding of the synthetic analogue in the enzyme active site. Treatment with SPP-002 also hampered the migration, adhesion, and invasion of MdA-MB-231 cells in vitro by suppressing the expression of signaling proteins involved in the cancer metastasis-associated integrin/FAK/paxillin pathway. In totality, these findings offer not only a novel structural scaffold but also valuable insights for the future development of more potent and selective ST inhibitors with potential therapeutic effects against tumor cancer metastasis.

关键词： Cancer metastasis Integrin-FAK-paxillin signaling pathway Lithocholic acid Sialyltransferase inhibitor

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A new manometer with Arduino

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Journal of physics: Conference Series 2021年第1期1719卷

作者： C Jaewijarn S Wuttiprom Ph.D. candidate in Science Education program Faculty of Science Ubon Ratchathani University Warin Chamrap Ubon Ratchathani 34190 Thailand Department of Physics Faculty of Science Ubon Ratchathani University Warin Chamrap Ubon Ratchathani 34190 Thailand Thailand Center of Excellence in Physics Commission on Higher Education Bangkok 10400 Thailand

Manometer, the U-shaped tube contains liquid, is the apparatus for measuring pressure. By reading the risen liquid level, the pressure can be obtained. Arduino is the microcontroller that plays a crucial role for physics instruction because the device is simple, inexpensive and accurate. Arduino can be connected with many types of probe, for example, lux meter, sound meter, pressure meter, etc. due to its application, teaching physics with Arduino can draw students' attention excellently. The purpose of the study was 1) to invent the new manometer with Arduino for measuring pressure at different level of dept and figuring out the buoyance force on the object 2) to improve students' understanding in pressure and buoyance force. The participants were 40 students. The method for the study was a one-group pretest-posttest design including 10 three-tier questions. The finding indicated that 1) the new manometer was handy and accurate 2) students' concept about pressure and buoyance force had been improved at the significant level of .05.

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Natural sweetener glycyrrhizin protects against precocious puberty by modulating the gut microbiome

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Life sciences 2024年 350卷 122789页

作者： Nguyen, Nam Nhat Lin, Chia-Yuan Tsai, Wan-Ling Huang, Hui-Yu Chen, Chung-Ming Tung, Yu-Tang Chen, Yang-Ching International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan Department of Food Science National Taiwan Ocean University Keelung 202 Taiwan Department of Family Medicine School of Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan Department of Health Promotion and Gerontological Care College of LOHAS Taipei University of Marine Technology New Taipei City 251 Taiwan Graduate Institute of Metabolism and Obesity Sciences Taipei Medical University Taipei 110 Taiwan Department of Pediatrics School of Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan Department of Pediatrics Taipei Medical University Hospital Taipei 110 Taiwan Graduate Institute of Biotechnology National Chung Hsing University Taichung 402 Taiwan Department of Family Medicine Wan Fang Hospital Taipei Medical University Taipei 116 Taiwan School of Nutrition and Health Sciences College of Nutrition Taipei Medical University Taipei 110 Taiwan Nutrition Research Center Taipei Medical University Hospital Taipei 110 Taiwan

Aims: Precocious puberty (PP) may lead to many adverse outcomes. Recent evidence suggests that PP is a gut–brain disease. On the other hand, the use of glycyrrhizin, a natural sweetener, has become popular in the past decade. Glycyrrhizin possesses various health benefits, but its impact on PP has yet to be investigated. We aimed to explore the protective effects of glycyrrhizin against PP in both humans (observational) and animals (interventional). Materials and methods: In the human cohort, we investigated the association between glycyrrhizin consumption and risk of PP. In the animal experiment, we observed puberty onset after feeding danazol-induced PP rats with glycyrrizin. Blood, fecal, and hypothalamic samples were harvested to evaluate potential mechanistic pathways. We also performed a fecal microbiota transplantation to confirm to causal relationship between glycyrrhizin and PP risk. Key findings: Glycyrrhizin exhibited a protective effect against PP in children (OR 0.60, 95%CI: 0.39–0.89, p = 0.013), primarily driven by its significance in girls, while no significant effect was observed in boys. This effect was consistent with findings in rodents. These benefits were achieved through the modulation of the gut microbiome, which functionally suppressed the hypothalamic–pituitary–gonadal axis and prevented PP progression. A fecal microbiota transplantation indicated that the causal correlation between glycyrrhizin intake and PP is mediated by the gut microbiome alterations. Significance: Our findings suggest that glycyrrhizin can protect against PP by altering the gut microbiome. Long term use of glycyrrhizin is safe and tolerable. Therefore, glycyrrhizin can serve as a safe and affordable complementary therapy for PP. © 2024 Elsevier Inc.

关键词： Fecal microbiota transplantation Glycyrrhizin Gut microbiome Gut-brain disease Hypothalamic-pituitary-gonadal axis Natural sweetener Precocious puberty

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Association of thyroid cancer with human papillomavirus infections

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Scientific Reports 2024年第1期14卷 1-7页

作者： Yang, Tzong-Hann Hung, Shih-Han Cheng, Yen-Fu Chen, Chin-Shyan Lin, Herng-Ching Department of Otorhinolaryngology Taipei City Hospital Taipei Taiwan Department of Speech Language and Audiology National Taipei University of Nursing and Health Taipei Taiwan Department of Otolaryngology-Head and Neck Surgery School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Center of General Education University of Taipei Taipei Taiwan Research Center of Data Science on Healthcare Industry College of Management Taipei Medical University Taipei Taiwan Department of Otolaryngology School of Medicine Taipei Medical University Taipei 110 Taiwan Department of Otolaryngology Wan Fang Hospital Taipei 110 Taiwan International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan Department of Medical Research Taipei Veterans General Hospital Taipei Taiwan Department of Otolaryngology-Head and Neck Surgery Taipei Veterans General Hospital Taipei Taiwan Department of Economics National Taipei University New Taipei City Taiwan School of Health Care Administration College of Management Taipei Medical University Taipei Taiwan Research Center of Sleep Medicine Taipei Medical University Hospital Taipei Taiwan

While Human Papillomavirus (HPV) particles have been detected in a small proportion of benign thyroid nodules or thyroid cancer cases, a role of HPV in these thyroid conditions has not been established. This study aims to investigate the association of HPV infection with thyroid cancer (TC) using a nationwide population-based study. We retrieved data for this case–control study from Taiwan's Longitudinal Health Insurance database 2010. The study sample included 3062 patients with TC and 9186 propensity-scored matched controls. We employed multivariate logistic regression models to quantitatively evaluate the association of TC with HPV infections after taking age, sex, monthly income, geographic location and urbanization level of the patient's residence, diabetes, hypertension, and hyperlipidemia into considerations. Chi-squared test revealed that there was a significant difference in the prevalence of prior HPV infections between patients with TC and controls (15.3% vs. 7.6%, p < 0.001). The adjusted odds ratio of prior HPV infections for patients with TC was 2.199 (95% CI = 1.939–2.492) relative to controls. The adjusted ORs of prior HPV infections for patients with TC was similar for males and females. Our research suggests a significant link between HPV infection and the development of TC. © 2023, The Author(s).

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Interaction of integrating land use systems on pig farming systems, West Papua-Indonesia;worth or worse?

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IOP Conference Series: Earth and Environmental science 2020年第1期492卷

作者： d A Iyai A Ako S N Sirajuddin Budiman Ph.D. Student of Animal Science Study Program Faculty of Animal Science Hasanuddin University Makassar Indonesia Animal Science Faculty Hasanuddin University Makassar Indonesia

In the pattern of livestock keeping systems, livestock can have free access path to natural resources such as forests, scrubs, water, natural shading, wastes, and residues. How they use and do interact with land use systems particularly the pigs, become the focus of this assessment. the study areas will cover four districts, i.e. Warmare, Prafi, Masni and Sidey. The total areas of study therefore is 1,022.67 km2 (102,266.54 ha). data collected from BPS board of Manokwari, Papua Barat. data were analyzed using Statistical descriptive and shown in tables. Pictures were drawn using Arc GIS and Microsoft Visio. There are 11 types of land use systems which have roles in ecosystem and livestock-human interaction. Land use was dominated by tropical forest and followed by oil palm plantation, communal land, transmigrate areas and arable land. Beef cattle present dominantly the land use systems in agro-complex of Prafi, followed by pigs and goat. Further study is needed to prove the effect of interaction on sustainability indicators, i.e. society, economic and environment.

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Interpretable network propagation with application to expanding the repertoire of human proteins that interact with SARS-CoV-2

arXiv

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arXiv 2020年

作者： Law, Jeffrey N. Akers, Kyle Tasnina, Nure della Santina, Catherine M. deutsch, Shay Kshirsagar, Meghana Klein-Seetharaman, Judith Crovella, Mark Rajagopalan, Padmavathy Kasif, Simon Murali, T.M. Interdisciplinary Ph.D. Program in Genetics Bioinformatics and Computational Biology BlacksburgVA United States Department of Computer Science Virginia Tech BlacksburgVA United States Department of Biomedical Engineering Boston University BostonMA United States Department of Mathematics University of California Los AngelesCA United States AI for Good Lab Microsoft RedmondWA United States Department of Chemistry Colorado School of Mines GoldenCO United States Department of Computer Science Boston University BostonMA United States Department of Chemical Engineering Virginia Tech BlacksburgVA United States

Background: Network propagation has been widely used for nearly 20 years to predict gene functions and phenotypes. despite the popularity of this approach, little attention has been paid to the question of provenance tracing in this context, e.g., determining how much any experimental observation in the input contributes to the score of every prediction. Results: We design a network propagation framework with two novel components and apply it to predict human proteins that directly or indirectly interact with SARS-CoV-2 proteins. First, we trace the provenance of each prediction to its experimentally validated sources, which in our case are human proteins experimentally determined to interact with viral proteins. Second, we design a technique that helps to reduce the manual adjustment of parameters by users. We find that for every top-ranking prediction, the highest contribution to its score arises from a direct neighbor in a human protein-protein interaction network. We further analyze these results to develop functional insights on SARS-CoV-2 that expand on known biology such as the connection between endoplasmic reticulum stress, HSPA5, and anti-clotting agents. Conclusions: We examine how our provenance tracing method can be generalized to a broad class of network-based algorithms. We provide a useful resource for the SARS-CoV-2 community that implicates many previously undocumented proteins with putative functional relationships to viral infection. This resource includes potential drugs that can be opportunistically repositioned to target these proteins. We also discuss how our overall framework can be extended to other, newly-emerging viruses. © 2020, CC BY-NC-SA.

关键词： SARS

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data-driven Two-Stage Framework for Identification and Characterization of different Antibiotic-Resistant Escherichia coli Isolates Based on Mass Spectrometry data

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Microbiology spectrum 2023年第3期11卷 e0347922页

作者： Chia-Ru Chung Hsin-Yao Wang Chun-Han Yao Li-Ching Wu Jang-Jih Lu Jorng-Tzong Horng Tzong-Yi Lee Department of Computer Science and Information Engineering National Central University Taoyuan Taiwan. Department of Laboratory Medicine Chang Gung Memorial Hospital at Linkou Taoyuan Taiwan. Ph.D. Program in Biomedical Engineering Chang Gung University Taoyuan Taiwan. Department of Biomedical Sciences and Engineering National Central University Taoyuan Taiwan. College of Medicine Chang Gung University Taoyuan Taiwan. Department of Medical Biotechnology and Laboratory Science Chang Gung University Taoyuan Taiwan. Department of Bioinformatics and Medical Engineering Asia University Taichung Taiwan. Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu Taiwan.

In clinical microbiology, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALdI-TOF MS) is frequently employed for rapid microbial identification. However, rapid identification of antimicrobial resistance (AMR) in Escherichia coli based on a large amount of MALdI-TOF MS data has not yet been reported. This may be because building a prediction model to cover all E. coli isolates would be challenging given the high diversity of the E. coli population. This study aimed to develop a MALdI-TOF MS-based, data-driven, two-stage framework for characterizing different AMRs in E. coli. Specifically, amoxicillin (AMC), ceftazidime (CAZ), ciprofloxacin (CIP), ceftriaxone (CRO), and cefuroxime (CXM) were used. In the first stage, we split the data into two groups based on informative peaks according to the importance of the random forest. In the second stage, prediction models were constructed using four different machine learning algorithms-logistic regression, support vector machine, random forest, and extreme gradient boosting (XGBoost). The findings demonstrate that XGBoost outperformed the other four machine learning models. The values of the area under the receiver operating characteristic curve were 0.62, 0.72, 0.87, 0.72, and 0.72 for AMC, CAZ, CIP, CRO, and CXM, respectively. This implies that a data-driven, two-stage framework could improve accuracy by approximately 2.8%. As a result, we developed AMR prediction models for E. coli using a data-driven two-stage framework, which is promising for assisting physicians in making decisions. Further, the analysis of informative peaks in future studies could potentially reveal new insights. Based on a large amount of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALdI-TOF MS) clinical data, comprising 37,918 Escherichia coli isolates, a data-driven two-stage framework was established to evaluate the antimicrobial resistance of E. coli. Five antibiotics, including a

关键词： MALdI-TOF MS antimicrobial resistance cephalosporin cephalosporins fluoroquinolones machine learning matrix-assisted laser desorption ionization–time of flight mass spectrometry penicillin penicillins

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Building and Maintaining Rapport to Engage Students

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The National Teaching & Learning Forum 2019年第6期28卷 6-7页

作者： Lynne N. Kennette School of Interdisciplinary Studies Durham College CONTACT: Lynne Kennette Ph.D. Professor of Psychology Program Coordinator General Arts and Science School of Interdisciplinary Studies Durham College B-wing #297C Oshawa Ontario CANADA

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Iterative Refinement and Oversampling for Low Rank Approximation

arXiv

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arXiv 2019年

作者： Pan, Victor Y. Luan, Qi Go, Soo Ph.D. Programs in Computer Science and Mathematics The Graduate Center of the City University of New York New YorkNY10036 United States Department of Computer Science Lehman College of the City University of New York BronxNY10468 United States

Iterative refinement is particularly popular for numerical solution of linear systems of equations. We extend it to Low Rank Approximation of a matrix (LRA) and observe close link of the resulting algorithm to oversampling techniques, commonly used in randomized LRA algorithms. We elaborate upon this link and revisit oversampling and some efficient randomized LRA algorithms. Applied with sparse sketch matrices they run significantly faster and in particular yield Very Low Rank Approximation (VLRA) at sublinear cost, using much fewer scalars and flops than the input matrix has entries. This is achieved at the price of deterioration of output accuracy, but according to our formal and empirical study subsequent oversampling improves accuracy to near-optimal level under the spectral norm for a large sub-class of matrices with fast decaying spectra of singular values. Copyright © 2019, The Authors. All rights reserved.

关键词： Linear systems

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CCL5 Protects Cortical Neuron Function by Regulating M2 Microglia Activation After Mild Traumatic Brain Injury

SSRN

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SSRN 2022年

作者： Tsai, Yih-Jeng Ho, Man-Hau Yen, Chia-Hung Wang, Jia-Yi Burnouf, Thierry Chen, Chia-Yen Wang, Yun Chiang, Yung-Hsiao Hoffer, Barry J. Chou, Szu-Yi Department of Otolaryngology Head and Neck Surgery Shin Kong Wu HoSu Memorial Hospital Taipei Taiwan School of Medicine Fu Jen Catholic University New Taipei City Taiwan Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University National Health Research Institute Taiwan Graduate Institute of Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan Department of Biological Science and Technology National Pingtung University of Science and Technology Neipu Pingtung91201 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan Department of Neurosurgery Taipei Medical University Hospital Taipei11031 Taiwan Neuroscience Research Center Taipei Medical University Taipei11031 Taiwan International PhD Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei Taiwan NeuroTMULille International Laboratory Taipei Medical University Taipei Taiwan International PhD Program in Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei Taiwan Brain and Consciousness Research Centre TMU Shuang Ho Hospital New Taipei City Taiwan Center for Neuropsychiatric Research National Health Research Institutes Zhunan Miaoli County Taiwan Department of Surgery School of Medicine College of Medicine Taipei Medical University 11031 Taiwan Department of Neurosurgery Case Western Reserve University School of Medicine ClevelandOH United States Scientist Emeritus National Institutes of Health United States International Master Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei Taiwan

Cytokines and chemokines play important roles in inflammation and repair following brain injury. M1 microglia are pro-inflammatory which produce cytokines and lead to neural injury;in contrast, M2 microglia are anti-inflammatory, release neurotrophic factors, and promote neural repair processes. Chemokine CCL5, increased after TBI, shows a neuroprotective function by reducing oxidative stress. CCL5 may contribute to the balance between oxidative stress and immune responses after brain injury. Herein, we investigated the role of CCL5 in microglial polarization after mild traumatic brain injury, focusing on the cerebral cortex.C57BL/6 and CCL5 knockout (CCL5-KO) mice were given a mild traumatic brain injury (TBI) using weight-drop. Neurological parameters such as motor and sensory functions were analyzed by mNSS score, accelerating rotarod, beam walking, and adhesive removal tests. Oxidative stress and neuron damage were measured by NAdph oxidase activity, hypoxyloprobe staining and FJC. Performance of motor and sensory functions in both WT and CCL5-KO mice were impaired after brain injury which recovered after 7 days-post-injury (dpi) in the WT group but only after 14 days in the CCL5-KO mouse group. RT-qPCR analysis revealed that pro-inflammation cytokines - IL-1β, TNF-α, and IL-6 were higher in CCL5-KO mice compared to WT mice at 4 and 14 dpi. In contrast, M2-like microglia markers - IL-10 and Agr-1 were increased in WT mouse cortical tissue at 4 dpi. Oxidative stress increased both M1 and M2- related cytokine expression in BV2 cells treated with H 2 O 2;CCL5 treatment increased M2- but suppressed M1- related cytokine gene activation. Intranasal delivery of CCL5 reduced neuronal oxidative stress, increased IL-10 expression and improved motor and sensory functions in CCL5-KO mice after brain *** summary, CCL5, which alters immune responses and protects neurons from TBI damage, has an important function in regulating M2-like microglial polarization during post-

关键词： Polarization

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