Category Archives: 研究發表

趙瑞益教授研究團隊發表研究成果於 Biochemical Pharmacology

連結網址：https://www.sciencedirect.com/science/article/pii/S0006295222003835

Abstract

Abstract

Colorectal cancer (CRC) is a leading cause and mortality worldwide. Aurora A and haspin kinases act pivotal roles in mitotic progression. However, the blockage of Aurora A and Haspin for CRC therapy is still unclear. Here we show that the Haspin and p-H3T3 protein levels were highly expressed in CRC tumor tissues of clinical patients. Overexpression of Haspin increased the protein levels of p-H3T3 and survivin in human CRC cells; conversely, the protein levels of p-H3T3 and survivin were decreased by the Haspin gene knockdown. Moreover, the gene knockdown of Aurora A induced abnormal chromosome segregation, mitotic catastrophe, and cell growth inhibition. Combined targeted by co-treatment of CHR6494, a Haspin inhibitor, and MLN8237, an Aurora A inhibitor, enhanced apoptosis and CRC tumor inhibition. MLN8237 and CHR6494 induced abnormal chromosome segregation and mitotic catastrophe. Meanwhile, MLN8237 and CHR6494 inhibited survivin protein levels but conversely induced p53 protein expression. Ectopic survivin expression by transfection with a survivin-expressed vector resisted the cell death in the MLN8237- and CHR6494-treated cells. In contrast, the existence of functional p53 increased the apoptotic levels by treatment with MLN8237 and CHR6494. Co-treatment of CHR6494 and MLN8237 enhanced the blockage of human CRC xenograft tumors in nude mice. Taken together, co-inhibition of Aurora A and Haspin enhances survivin inhibition, p53 pathway induction, mitotic catastrophe, apoptosis and tumor inhibition that may provide a potential strategy for CRC therapy.

陳亭妏副教授研究團隊發表研究成果於 Bioinformatics

連結網址：https://academic.oup.com/bioinformatics/article/38/18/4286/6649618

Abstract

Motivation: Microbiota analyses have important implications for health and science. These analyses make use of 16S/18S rRNA gene sequencing to identify taxa and predict species diversity. However, most available tools for analyzing microbiota data require adept programming skills and in-depth statistical knowledge for proper implementation. While long-read amplicon sequencing can lead to more accurate taxa predictions and is quickly becoming more common, practitioners have no easily accessible tools with which to perform their analyses.

Results: We present MOCHI, a GUI tool for microbiota amplicon sequencing analysis. MOCHI preprocesses sequences, assigns taxonomy, identifies different abundant species and predicts species diversity and function. It takes either taxonomic count table or FASTQ of partial 16S/18S rRNA or full-length 16S rRNA gene as input. It performs analyses in real time and visualizes data in both tabular and graphical formats.

Availability and implementation: MOCHI can be installed to run locally or accessed as a web tool at https://mochi.life.nctu.edu.tw

柯泰名助理教授研究團隊發表研究成果於 Clin Transl Med.

連結網址：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547115/

Summary

Ankylosing spondylitis (AS) is a chronic rheumatic disease that causes disability and severe impairment in the quality of life, especially in females. However, almost nothing is known about how large heterogenous circulating immune cells are involved in developing AS. Here we used droplet-based single-cell sequencing for multi-omic profiling of PBMCs obtained from female patients and sex-matched healthy individuals and performed multimodal single-cell analyses including single-cell-level unbiased transcriptome, surface protein expression, pseudotemporal trajectory analysis, cell-cell interaction analysis, and T-cell receptor repertoire. By applying multiple filtering strategies, we selected common single-cell blood features across the patients to reveal a unique T-cell state wherein GIMAP7 was up-regulated and NFKBIA was down-regulated. Furthermore, we identified a panel of cell-surface markers and dominant T-cell clonotypes on this unique T-cell subset (NFKBIA- GIMAP7+). We identified a unique VEGI signalling pathway between the T-cells and NK cells that uncovered potential triggers for developing exclusive T-cell states in female patients with AS. This finding could be valuable for developing innovative therapies that selectively target the aberrant immune response in female patients with AS.

陳亭妏助理教授研究團隊發表研究成果於 Journal of Infection

連結網址：https://www.sciencedirect.com/science/article/pii/S0163445322005175?via%3Dihub

Summary

Objectives: RNA therapeutics is an emerging field that widens the range of treatable targets and would improve disease outcome through bypassing the antibiotic bactericidal targets to kill Mycobacterium tuberculosis (M.tb).
Methods: We screened for microRNA with immune-regulatory functions against M.tb by next generation sequencing of peripheral blood mononuclear cells, followed by validation in an independent cohort.
Results: Twenty three differentially expressed microRNAs were identified between 12 active pulmonary TB patients and 4 healthy subjects, and 35 microRNAs before and after 6-month anti-TB therapy. Enriched predicted target pathways included proteoglycan, HIF-1 signaling, longevity-regulating, central carbon metabolism, and autophagy. We validated miR-431–3p down-regulation and miR-1303 up-regulation
accompanied with corresponding changes in their predicted target genes in an independent validation cohort of 46 active TB patients, 30 latent TB infection subjects, and 24 non-infected healthy subjects. In vitro experiments of transfections with miR-431–3p mimic/miR-1303 short interfering RNA in THP-1 cells under ESAT-6 stimuli showed that miR-431–3p and miR-1303 were capable to augment and suppress autophagy/apoptosis/phagocytosis of macrophage via targeting MDR1/MMP16/RIPOR2 and ATG5, respectively.
Conclusions: This study provides a proof of concept for microRNA-based host-directed immunotherapy for active TB disease. The combined miR-431–3p over-expression and miR-1303 knock-down revealed new vulnerabilities of treatment-refractory TB disease.

謝仁俊教授研究團隊發表研究成果於Hum Brain Mapp

連結網址：https://pubmed.ncbi.nlm.nih.gov/36005832/

Abstract

Abstract: Numerous studies have reported that long-term musical training can affect brain functionality and induce structural alterations in the brain. Singing is a form of vocal musical expression with an unparalleled capacity for communicating emotion; however, there has been relatively little research on neuroplasticity at the network level in vocalists (i.e., noninstrumental musicians). Our objective in this study was to elucidate changes in the neural network architecture following long-term training in the musical arts. We employed a framework based on graph theory to depict the connectivity and efficiency of structural networks in the brain, based on diffusion-weighted images obtained from 35 vocalists, 27 pianists, and 33 nonmusicians. Our results revealed that musical training (both voice and piano) could enhance connectivity among emotion-related regions of the brain, such as the amygdala. We also discovered that voice training reshaped the architecture of experience-dependent networks, such as those involved in vocal motor control, sensory feedback, and language processing. It appears that vocal-related changes in areas such as the insula, paracentral lobule, supramarginal gyrus, and putamen are associated with functional segregation, multisensory integration, and enhanced network interconnectivity. These results suggest that long-term musical training can strengthen or prune white matter connectivity networks in an experience-dependent manner.

蘇昱誠助理教授研究團隊發表研究成果於Communications Chemistry

連結網址：https://www.nature.com/articles/s42004-022-00709-0

Abstract

Covalent attachment of methoxy poly(ethylene) glycol (mPEG) to therapeutic molecules is widely employed to improve their systemic circulation time and therapeutic efficacy. mPEG, however, can induce anti-PEG antibodies that negatively impact drug therapeutic effects. However, the underlying mechanism for specific binding of antibodies to mPEG remains unclear. Here, we determined the first co-crystal structure of the humanized 15-2b anti-mPEG antibody in complex with mPEG, which possesses a deep pocket in the antigen-binding site to accommodate the mPEG polymer. Structural and mutational analyses revealed that mPEG binds to h15-2b via Van der Waals and hydrogen bond interactions, whereas the methoxy group of mPEG is stabilized in a hydrophobic environment between the VH:VL interface. Replacement of the heavy chain hydrophobic V37 residue with a neutral polar serine or threonine residue offers additional hydrogen bond interactions with methoxyl and hydroxyl groups, resulting in cross-reactivity to mPEG and OH-PEG. Our findings provide insights into understanding mPEG-binding specificity and antigenicity of anti-mPEG antibodies.

林奇宏教授研究團隊發表研究成果於 Nature communications
連結:https://www.nature.com/articles/s41467-022-31825-z
Abstract
Regulation of fatty acid uptake, lipid production and storage, and metabolism of lipid droplets (LDs), is closely related to lipid homeostasis, adipocyte hypertrophy and obesity. We report here that stomatin, a major constituent of lipid raft, participates in adipogenesis and adipocyte maturation by modulating related signaling pathways. In adipocyte-like cells, increased stomatin promotes LD growth or enlargements by facilitating LD-LD fusion. It also promotes fatty acid uptake from extracellular environment by recruiting effector molecules, such as FAT/CD36 translocase, to lipid rafts to promote internalization of fatty acids. Stomatin transgenic mice fed with high-fat diet exhibit obesity, insulin resistance and hepatic impairments; however, such phenotypes are not seen in transgenic animals fed with regular diet. Inhibitions of stomatin by gene knockdown or OB-1 inhibit adipogenic differentiation and LD growth through downregulation of PPARγ pathway. Effects of stomatin on PPARγ involves ERK signaling; however, an alternate pathway may also exist.

蕭育源教授研究團隊發表研究成果於 Nature communications

連結: https://www.nature.com/articles/s41467-020-20853-2

Abstract

The exonuclease activity of Apurinic/apyrimidinic endonuclease 1 (APE1) is responsible for processing matched/mismatched terminus in various DNA repair pathways and for removing nucleoside analogs associated with drug resistance. To fill in the gap of structural basis for exonucleolytic cleavage, we determine the APE1-dsDNA complex structures displaying end-binding. As an exonuclease, APE1 does not show base preference but can distinguish dsDNAs with different structural features. Integration with assaying enzyme activity and binding affinity for a variety of substrates reveals for the first time that both endonucleolytic and exonucleolytic cleavage can be understood by an induced space-filling model. Binding dsDNA induces RM (Arg176 and Met269) bridge that defines a long and narrow product pocket for exquisite machinery of substrate selection. Our study paves the way to comprehend end-processing of dsDNA in the cell and the drug resistance relating to APE1.

尤禎祥教授研究團隊發表研究成果Time-resolved Infrared Characterization on the Photolysis of Roussin’s Red Phenyl Ester in Different Solvents於Journal of Photochemistry and Photobiology A: Chemistry