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Biosensors 2023年第10期13卷 929-929页

作者： Chen, Hsiu-Mei Tsai, Yi-Hsuan Hsu, Chien-Yi Wang, Yong-Yi Hsieh, Cheng-En Chen, Jin-Hua Chang, Yu-Sheng Lin, Ching-Yu Department of Chemical Engineering National Taiwan University of Science and Technology Taipei10607 Taiwan Department of Family Medicine Wan Fang Hospital Taipei Medical University Taipei11696 Taiwan Division of Cardiology and Cardiovascular Research Center Department of Internal Medicine Taipei Medical University Hospital Taipei11031 Taiwan Division of Cardiology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Taipei Heart Institute Taipei Medical University Taipei11031 Taiwan Graduate Institute of Data Science College of Management Taipei Medical University Taipei11031 Taiwan Office of Data Science Taipei Medical University Taipei11031 Taiwan Division of Allergy Immunology and Rheumatology Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City23561 Taiwan Division of Allergy Immunology and Rheumatology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan School of Medical Laboratory Science and Biotechnology College of Medical Science and Technology Taipei Medical University Taipei11031 Taiwan Ph.D. Program in Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taipei11031 Taiwan

An effective early diagnosis is important for rheumatoid arthritis (RA) management. This study reveals a novel RA detection method using bacteriorhodopsin as a photoelectric transducer, a light-driven proton pump in purple membranes (PMs). It was devised by covalently conjugating a PM monolayer-coated electrode with a citrullinated-inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3)542–556 peptide that recognizes the serum RA-associated autoantibodies. The direct serum coating decreased the photocurrents in the biosensor, with the reduction in the photocurrent caused by coating with an RA-patient serum that is significantly larger than that with a healthy-control serum (38.1% vs. 20.2%). The difference in the reduction in the photocurrent between those two serum groups widened after the serum-coated biosensor was further labeled with gold nanoparticle (AuNP)-conjugated anti-IgA (anti-IgA-AuNP) (53.6% vs. 30.6%). Both atomic force microscopic (AFM) and Raman analyses confirmed the sequential peptide, serum, and anti-IgA-AuNP coatings on the PM-coated substrates. The reductions in the photocurrent measured in both the serum and anti-IgA-AuNPs coating steps correlated well with the results using commercial enzyme-linked immunosorbent assay kits (Spearman rho = 0.805 and 0.787, respectively), with both a sensitivity and specificity close to 100% in both steps. It was shown that an RA diagnosis can be performed in either a single- or two-step mode using the developed biosensor. © 2023 by the authors.

关键词： Peptides

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Glycyrrhizic acid conjugates with amino acid methyl esters target the main protease, exhibiting antiviral activity against wild-type and nirmatrelvir-resistant SARS-CoV-2 variants

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Antiviral research 2024年 227卷 105920页

作者： Uyen Nguyen phuong Le Yu-Jen Chang Chih-Hao Lu Yeh Chen Wen-Chi Su Shao-Ting Chao Lia A Baltina Svetlana F Petrova Sin-Rong Li Mien-Chie Hung Michael M C Lai Lidia A Baltina Cheng-Wen Lin Graduate Institute of Biological Science and Technology China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology China Medical University Taichung Taiwan. The Ph.D. Program of Biotechnology and Biomedical Industry China Medical University Taichung Taiwan. The Ph.D. Program of Biotechnology and Biomedical Industry China Medical University Taichung Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu Taiwan. Department of Food Science and Biotechnology National Chung Hsing University Taichung 402 Taiwan. Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan. Ufa Institute of Chemistry Ufa Federal Research Center of the Russian Academy of Sciences Russia. Department of Laboratory Medicine China Medical University Hospital Taichung 404327 Taiwan. Research Center for Cancer Biology China Medical University Taichung 404327 Taiwan Center for Molecular Medicine China Medical University Hospital Taichung 404327 Taiwan. Institute of Molecular Biology Academia Sinica Taipei 115201 Taiwan. Ufa Institute of Chemistry Ufa Federal Research Center of the Russian Academy of Sciences Russia. Electronic address: baltina@anrb.ru. Department of Medical Laboratory Science and Biotechnology China Medical University Taichung Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan. Electronic address: cwlin@mail.cmu.edu.tw.

COVId-19 pandemic is predominantly caused by SARS-CoV-2, with its main protease, Mpro, playing a pivotal role in viral replication and serving as a potential target for inhibiting different variants. In this study, potent Mpro inhibitors were identified from glycyrrhizic acid (GL) derivatives with amino acid methyl/ethyl esters. Out of the 17 derivatives semisynthesized, Compounds 2, 6, 9, and 15, with methionine methyl esters, d-tyrosine methyl esters, glutamic acid methyl esters, and methionines in the carbohydrate moiety, respectively, significantly inhibited wild-type SARS-CoV-2 Mpro-mediated proteolysis, with IC50 values ranging from 0.06 μM to 0.84 μM. They also demonstrated efficacy in inhibiting trans-cleavage by mutant Mpro variants (Mpro_P132H, Mpro_E166V, Mpro_P168A, Mpro_Q189I), with IC50 values ranging from 0.05 to 0.92 μM, surpassing nirmatrelvir (IC50: 1.17-152.9 μM). Molecular modeling revealed stronger interactions with Valine166 in the structural complex of Mpro_E166V with the compounds compared to nirmatrelvir. Moreover, these compounds efficiently inhibited the post-entry viral processes of wild-type SARS-CoV-2 single-round infectious particles (SRIPs), mitigating viral cytopathic effects and reducing replicon-driven GFP reporter signals, as well as in vitro infectivity of wild-type, Mpro_E166V, and Mpro_Q189I SRIPs, with EC50 values ranging from 0.02 to 0.53 μM. However, nirmatrelvir showed a significant decrease in inhibiting the replication of mutant SARS-CoV-2 SRIPs carrying Mpro_E166V (EC50: >20 μM) and Mpro_Q189I (EC50: 13.2 μM) compared to wild-type SRIPs (EC50: 0.06 μM). Overall, this study identifies four GL derivatives as promising lead compounds for developing treatments against various SARS-CoV-2 strains, including Omicron, and nirmatrelvir-resistant variants.

关键词： Glycyrrhizic acid derivative Inhibitor Mpro Nirmatrelvir-resistant variant Omicron SARS-CoV-2

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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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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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Enhancing miso production with optimized puffed-rice koji and its biological function evaluation

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Food Bioscience 2024年 60卷

作者： Lin, Shin-Ping Chou, Yu-Chieh Chen, Chiao-En Lai, Yen-Tso Hsieh, Chen-Che Tsai, Tsung-Yu Lin, Yun-Hsin Santoso, Shella Permatasari Lin, Hui-Wen Cheng, Kuan-Chen School of Food Safety Taipei Medical University 250 Wu-Hsing Street Taipei 11031 Taiwan Research Center of Biomedical Device Taipei Medical University 250 Wu-Hsing Street Taipei 11031 Taiwan TMU Research Center for Digestive Medicine Taipei Medical University 250 Wu-Hsing Street Taipei 11031 Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University 250 Wu-Hsing Street Taipei 11031 Taiwan Institute of Food Science and Technology National Taiwan University 1 Roosevelt Rd. Sec. 4 Taipei 10617 Taiwan Department of Food and Nutrition Providence University 200 Sec. 7 Taiwan Boulevard Shalu Dist. Taichung 43301 Taiwan Institute of Biotechnology National Taiwan University 1 Roosevelt Rd. Sec. 4 Taipei 10617 Taiwan Department of Food Science Fu Jen Catholic University 510 Zhongzheng Rd. Xinzhuang Dist. New Taipei City 242062 Taiwan Department of Chemical Engineering Widya Mandala Surabaya Catholic University 37 Jl. Kalijudan 37 East Java Surabaya 60114 Indonesia Collaborative Research Center for Zero Waste and Sustainability 37 Jl. Kalijudan East Java Surabaya 60114 Indonesia Department of Optometry Asia University 500 Lioufeng Rd. Wufeng Taichung 41354 Taiwan Department of Medical Research China Medical University Hospital China Medical University 91 Hsueh-Shih Road Taichung 40402 Taiwan

In order to enhance enzyme activities of koji and further improve the health benefits and nutritional value of miso, puffed rice was used to prepare koji with optimization of fermentation utilizing response surface methodology (RSM), and the optimized puffed rice koji was used to produce miso and low-salt miso. Results showed that β-glucosidase activity increased by 1.98-fold after RSM optimization. The optimized puffed rice koji also showed the highest β-amylase and protease activities (237.1 and 968.8 units/g, respectively) compared to rice koji (108.7 and 637.4 units/g, respectively). Moreover, miso made from puffed-rice koji presented a much higher polyphenol content, antioxidant activity, and aglycone conversion. These findings clarified the relationship between changes in enzyme activities in koji and the important components of miso, and also advance solid-state fermentation research and development of functional miso. © 2024

关键词： Aspergillus oryzae Koji Miso Puffed rice Solid-state fermentation β-glucosidase

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Anethole mitigates H2O2-induced inflammation in HIG-82 synoviocytes by suppressing the aquaporin 1 expression and activating the protein kinase A pathway

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Environmental Toxicology 2024年第2期39卷 965-978页

作者： Huang, Tai-Lung Chang, Yu-Chun Tsai, Bruce Chi-Kang Chen, Tung-Sheng Kao, Shih-Wen Tsai, Yung-Yun Lin, Shinn-Zong Yao, Chun-Hsu Lin, Kuan-Ho Kuo, Wei-Wen Huang, Chih-Yang Department of Biological Science and Technology College of Life Sciences China Medical University Taichung Taiwan Department of Orthopedics Chung-Kang Branch Cheng Ching General Hospital Taichung Taiwan Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan School of Life Science National Taiwan Normal University Taipei Taiwan Department of Orthopaedic Surgery Chung-Shan Medical University Hospital Taichung Taiwan Department of Physical Therapy Asia University Taichung Taiwan Department of Neurosurgery Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Bioinnovation Center Buddhist Tzu Chi Medical Foundation Hualien Taiwan Department of Biomedical Imaging and Radiological Science China Medical University Taichung Taiwan School of Chinese Medicine China Medical University Taichung Taiwan Biomaterials Translational Research Center China Medical University Hospital Taichung Taiwan Department of Bioinformatics and Medical Engineering Asia University Taichung Taiwan Division of Cardiovascular Medicine Department of Internal Medicine China Medical University Hospital Taichung Taiwan Department of Emergency Medicine China Medical University Hospital Taichung Taiwan College of Medicine China Medical University Taichung Taiwan Ph.D. Program for Biotechnology Industry China Medical University Taichung Taiwan Department of Medical Research China Medical University Hospital China Medical University Taichung Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan Center of General Education Buddhist Tzu Chi Medical Foundation Tzu Chi University of Science and Technology Hualien Taiwan

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease affecting approximately 1% of the global population, with a higher prevalence in women than in men. Chronic inflammation and oxidative stress play pivotal roles in the pathogenesis of RA. Anethole, a prominent compound derived from fennel (Foeniculum vulgare), possesses a spectrum of therapeutic properties, including anti-arthritic, anti-inflammatory, antioxidant, and tumor-suppressive effects. However, its specific impact on RA remains underexplored. This study sought to uncover the potential therapeutic value of anethole in treating RA by employing an H2O2-induced inflammation model with HIG-82 synovial cells. Our results demonstrated that exposure to H2O2 induced the inflammation and apoptosis in these cells. Remarkably, anethole treatment effectively countered these inflammatory and apoptotic processes triggered by H2O2. Moreover, we identified the aquaporin 1 (AQP1) and protein kinase A (PKA) pathway as critical regulators of inflammation and apoptosis. H2O2 stimulation led to an increase in the AQP1 expression and a decrease in p-PKA-C, contributing to cartilage degradation. Conversely, anethole not only downregulated the AQP1 expression but also activated the PKA pathway, effectively suppressing cell inflammation and apoptosis. Furthermore, anethole also inhibited the enzymes responsible for cartilage degradation. In summary, our findings highlight the potential of anethole as a therapeutic agent for mitigating H2O2-induced inflammation and apoptosis in synovial cells, offering promising prospects for future RA treatments. © 2023 Wiley Periodicals LLC.

关键词： Cell death

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Calycosin Enhances Heat Shock Related-Proteins in H9c2 Cells to Modulate Survival and Apoptosis against Heat Shock

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The American journal of Chinese medicine 2024年第4期52卷 1173-1193页

作者： Pei-Fang Lai Ramasamy Mahendran Bruce Chi-Kang Tsai Cheng-You Lu Chia-Hua Kuo Kuan-Ho Lin Shang-Yeh Lu Yu-Ling Wu Yung-Ming Chang Wei-Wen Kuo Chih-Yang Huang Department of Emergency Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien 970 Taiwan. Department of Medicine Tzu Chi University Hualien 970 Taiwan. Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien 970 Taiwan. Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung 402 Taiwan. Laboratory of Exercise Biochemistry University of Taipei Taipei 111 Taiwan. Institute of Sports Sciences University of Taipei Taipei 111 Taiwan. School of Physical Education and Sports Science Soochow University Suzhou 215021 China. Department of Kinesiology and Health College of William and Mary Williamsburg VA 23185 USA. Department of Emergency Medicine China Medical University Hospital Taichung 404 Taiwan. College of Medicine China Medical University Taichung 406 Taiwan. Division of Cardiovascular Medicine Department of Internal Medicine China Medical University Hospital Taichung 404 Taiwan. The School of Chinese Medicine for Post-Baccalaureate I-Shou University 840 Kaohsiung Taiwan. Chinese Medicine Department E-DA Hospital Kaohsiung 824 Taiwan. 1PT Biotechnology Co. Ltd. Taichung 433 Taiwan. Department of Biological Science and Technology College of Life Sciences China Medical University Taichung 406 Taiwan. Ph.D. Program for Biotechnology Industry China Medical University Taichung 406 Taiwan. School of Pharmacy China Medical University Taichung 406 Taiwan. Graduate Institute of Biomedical Sciences China Medical University Taichung 406 Taiwan. Department of Medical Laboratory Science and Biotechnology Asia University Taichung 413 Taiwan. Center of General Education Buddhist Tzu Chi Medical Foundation Tzu Chi University of Science and Technology Hualien 970 Taiwan. Department of Medical Research China Medical University Hospital China Medical University Taichung 404 Taiwan.

Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2[Formula: see text]h, followed by protein degradation after 4[Formula: see text]h. Hence, a heat shock damage duration of 4[Formula: see text]h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells.

关键词： Astragalus Membranaceus Calycosin Cardiomyocyte Heart Protection Heat Shock Heat Shock-Related Protein

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The Critical Role of Galectin-12 in Modulating Lipid Metabolism in Sebaceous Glands

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The Journal of investigative dermatology 2023年第6期143卷 913-924.e4页

作者： Ching-Han Tsao Wei-Chen Hsieh Feng-Jen Lin Ri-Yao Yang Meng-Ting Chang Maria Karmella Apaya Lie-Fen Shyur Liang-Yin Ke Christos C Zouboulis Fu-Tong Liu Institute of Biomedical Sciences Academia Sinica Taipei Taiwan Ph.D. Program in Translational Medicine Kaohsiung Medical University and Academia Sinica Taipei Taiwan. Institute of Biomedical Sciences Academia Sinica Taipei Taiwan. Graduate Institute of Immunology College of Medicine National Taiwan University Taipei Taiwan. Department of Molecular & Cellular Oncology The University of Texas MD Anderson Cancer Center Houston Texas USA. Agricultural Biotechnology Research Center Academia Sinica Taipei Taiwan. Ph.D. Program in Translational Medicine Kaohsiung Medical University and Academia Sinica Taipei Taiwan Department of Medical Laboratory Science and Biotechnology College of Health Sciences Kaohsiung Medical University Kaohsiung Taiwan. Departments of Dermatology Venereology Allergology and Immunology Dessau Medical Center Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg Dessau Germany. Department of Dermatology School of Medicine University of California-Davis Sacramento California USA. Electronic address: ftliu@ibms.sinica.edu.tw.

Sebaceous glands play an important role in maintaining the skin barrier function by producing lipids. dysregulated lipid production in these glands may contribute to the pathogenesis of human skin diseases. Galectin-12, a member of the β-galactoside‒binding lectin family, is preferentially expressed in adipocytes, where it regulates adipogenesis and functions as an intrinsic negative regulator of lipolysis. It is also expressed by sebocytes and contributes to the proliferation of this cell type. In this study, we show the association between galectin-12 expression and sebocyte differentiation. Galectin-12 knockdown in a human sebocyte cell line reduced lipogenesis and decreased the production of cholesteryl esters, triglycerides, free fatty acids, and cholesterol. Metabolomic analysis of skin surface lipids showed that the levels of the lipids mentioned earlier decreased in sebaceous gland‒specific galectin-12‒knockout mice compared with that in wild-type mice. In addition, galectin-12 positively regulated peroxisome proliferator‒activated receptor-γ transcriptional activity in sebocytes stimulated with fatty acids. downregulating galectin-12 suppressed the expression of peroxisome proliferator‒activated receptor-γ target genes-acetyl-coenzyme A synthetase 2 gene ACS2 and diacylglycerol O-acyltransferase 1 gene dGAT1-that are required for fatty acid activation and cholesterol and triglyceride biosynthesis. In conclusion, galectin-12 is a positive regulator of sebaceous lipid metabolism with a potential role in the maintenance of skin homeostasis.

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Integration of MRI and somatosensory evoked potentials facilitate diagnosis of spinal cord compression

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Scientific Reports 2023年第1期13卷 1-12页

作者： Sun, Shu-Pin phang, Chun-Ren Tzou, Shey-Cherng Chen, Chang-Mu Ko, Li-Wei International Ph.D. Program in Interdisciplinary Neuroscience (UST) College of Biological Science and Technology National Yang Ming Chiao Tung University 734 Engineering Bldg. 5 1001 Daxue Road Hsinchu 30010 Taiwan Department of Medical Research National Taiwan University Hospital Hsin-Chu Branch Hsinchu 300 Taiwan Institute of Molecular Medicine and Bioengineering National Yang Ming Chiao Tung University Hsinchu 300 Taiwan Department of Surgery College of Medicine and Hospital National Taiwan University No. 7 Zhongshan South Road Taipei 10002 Taiwan Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B) College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu 300 Taiwan Institute of Electrical and Control Engineering Department of Electronics and Electrical Engineering National Yang Ming Chiao Tung University Hsinchu 300 Taiwan Department of Biomedical Science and Environment Biology and the Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung 807 Taiwan

This study aimed to integrate magnetic resonance imaging (MRI) and related somatosensory evoked potential (SSEP) features to assist in the diagnosis of spinal cord compression (SCC). MRI scans were graded from 0 to 3 according to the changes in the subarachnoid space and scan signals to confirm differences in SCC levels. The amplitude, latency, and time–frequency analysis (TFA) power of preoperative SSEP features were extracted and the changes were used as standard judgments to detect neurological function changes. Then the patient distribution was quantified according to the SSEP feature changes under the same and different MRI compression grades. Significant differences were found in the amplitude and TFA power between MRI grades. We estimated three degrees of amplitude anomalies and power loss under each MRI grade and found the presence or absence of power loss occurs after abnormal changes in amplitude only. For SCC, few integrated approach combines the advantages of both MRI and evoked potentials. However, integrating the amplitude and TFA power changes of SSEP features with MRI grading can help in the diagnosis and speculate progression of SCC. © 2023, The Author(s).

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HER2 amplification in colorectal cancer with brain metastasis: A propensity score matching study

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European journal of cancer (Oxford, England : 1990) 2023年 181卷 62-69页

作者： Po-Chuan Chen Yu-Min Yeh Chun-Ting Chu Pei-Fang Su Pin-Hsuan Chiu Bo-Wen Lin Shang-Hung Chen Peng-Chan Lin Chung-Ta Lee Helen H W Chen Chien-Chin Chen Division of Colorectal Surgery Department of Surgery National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan. Department of Oncology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan. Division of Colorectal Surgery Department of Surgery Ditmanson Medical Foundation Chia-Yi Christian Hospital Chiayi 600 Taiwan. Department of Statistics National Cheng Kung University Tainan 701 Taiwan. The Center of Quantitative Sciences Clinical Medicine Research Center National Cheng Kung University Hospital Tainan 704 Taiwan. Department of Oncology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan National Institute of Cancer Research National Health Research Institute Tainan 704 Taiwan. Department of Genomic Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan Department of Computer Science and Information Engineering College of Electrical Engineering and Computer Science National Cheng Kung University Tainan 704 Taiwan. Department of Pathology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan. Department of Oncology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan. Electronic address: helen@mail.ncku.edu.tw. Department of Pathology Ditmanson Medical Foundation Chia-Yi Christian Hospital Chiayi 600 Taiwan Department of Cosmetic Science Chia Nan University of Pharmacy and Science Tainan 717 Taiwan Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan 701 Taiwan Ph.D. Program in Translational Medicine Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung 40227 Taiwan. Electronic address: hlmarkc@gmail.c

BACKGROUNd:The association between human epidermal growth factor receptor-2 (HER2) amplification and brain metastasis (BM) in patients having colorectal cancer (CRC) has been suggested but not yet established. This study investigated the expression patterns of HER2, its association with BM, and its prognostic value in patients having CRC. METHOdS:We retrospectively identified 99 patients having metastatic CRC (mCRC) and BM (the BM cohort) and compared them with a cohort of 249 patients having mCRC and without BM (the stage IV cohort) by propensity score matching. Immunohistochemical studies of HER2 on all available paraffin-embedded tumour samples, either from the primary tumour, the metastasis (brain and/or extracranial sites) or both, were performed and analysed. HER2 fluorescent in situ hybridisation was applied when necessary. The expression of HER2 was compared and correlated with survival. RESULTS:HER2 amplifications were detected in 16 (18.4%) of 87 and 9 (3.6%) of 249 patients who had specimens available in the BM and stage IV cohorts, respectively (P < .001). After propensity score matching, HER2 amplification was significantly associated with BM (odds ratio: 5.38, P = .003). HER2 heterogeneity was frequently observed not only at the single tumour level but also in paired tumour samples. A marginally significant longer survival since BM was found in patients having HER2-amplified mCRC than in those without (P = .07). CONCLUSIONS:HER2 amplification was significantly associated with BM in patients having mCRC and might have prognostic value for survival since BM. Given the heterogeneity of HER2 expression, the testing of HER2 status on available tissues from both primary and metastatic tumours should be encouraged.

关键词： Brain metastasis Colorectal cancer HER2 amplification Heterogeneity Propensity score matching

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