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diterpenoids and Their Glycosides from the Stems ofTinospora crispawith Beta-Cell Protective Activity

Journal of Natural Products 2023年第6期86卷 1437-1448页

作者： Sio-Hong Lam Hui-Kang Liu Shih-Yuan Chung Jia-Ling Chang Mao-Xuan Hong Sheng-Chu Kuo Chih-Chuang Liaw School of Pharmacy College of Medicine National Cheng Kung University Tainan 70101 Taiwan Division of Basic Chinese Medicine National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei 112 Taiwan Ph.D. Program in the Clinical Drug Development of Herbal Medicine Taipei Medical University Taipei 11031 Taiwan Graduate Institute of Pharmaceutical Chemistry China Medical University Taichung 404 Taiwan Department of Marine Biotechnology and Resource National Sun Yat-sen University Kaohsiung 80424 Taiwan Department of Science Application and Dissemination National Taichung University of Education Taichung 403 Taiwan Graduate Institute of Natural Products Kaohsiung Medical University Kaohsiung 807 Taiwan Graduate Institute of Pharmacognosy Taipei Medical University Taipei 11031 Taiwan

Seven previously undescribed diterpenoids, tinocrisposides A–d (1–4) and borapetic acids A (5), B (6), and C (7), together with 16 known compounds, were isolated from the stem ofTinospora crispa(Menispermaceae). The structures of the new isolates were elucidated by spectroscopic and chemical methods. The β-cell protective effect of the tested compounds was examined on insulin-secreting BRIN-Bd11 cells under dexamethasone treatment. diterpene glycosides12,14–16, and18presented a substantial protective effect on BRIN-Bd11 cells treated with dexamethasone in a dose-dependent manner. Compounds4and17with two sugar moieties exhibited clear protective effects on β-cells.

关键词： Alkyls Carbohydrates Carbon Chemical structure Nuclear magnetic resonance spectroscopy

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Overall mortality risk analysis for rectal cancer using deep learning-based fuzzy systems

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Computers in Biology and Medicine 2023年 157卷 106706-106706页

作者： Yang, Cheng-Hong Chen, Wen-Ching Chen, Jin-Bor Huang, Hsiu-Chen Chuang, Li-Yeh Department of Information Management Tainan University of Technology Tainan Taiwan Department of Electronic Engineering National Kaohsiung University of Science and Technology Kaohsiung Taiwan Ph. D. Program in Biomedical Engineering Kaohsiung Medical University Kaohsiung Taiwan School of Dentistry Kaohsiung Medical University Kaohsiung Taiwan Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung Taiwan Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung Taiwan Department of Community Health Chia-Yi Christian Hospital Chia-Yi City Taiwan Department of Chemical Engineering & Institute of Biotechnology and Chemical Engineering I-Shou University Kaohsiung Taiwan

Colorectal cancer is a leading cause of cancer mortality worldwide, with an increasing incidence rate in developing countries. Integration of genetic information with cancer therapy guidance has shown promise in cancer treatment, indicating its potential as an essential tool in translation oncology. However, the high-throughput analysis and variability of genomic data poses a major challenge to conventional analytic approaches. In this study, we propose an advanced analytic approach, named "Fuzzy-based RNNCoxph," incorporated fuzzy logic, recurrent neural networks (RNNs), and Cox proportional hazards regression (Coxph) for detecting missense variants associated with high-risk of all-cause mortality in rectum adenocarcinoma. The test data set was downloaded from "Rectum adenocarcinoma, TCGA-REAd" the Genomic data Commons (GdC) portal. In this study, four model-based risk score models were derived using RNN, Coxph, RNNCoxphAddition, and RNNCoxphMultiplication. The RNNCoxphAddition and RNNCoxphMultiplication models were obtained as the sum and product of the RNN risk degree matrix and the Coxph risk degree matrix, respectively. Moreover, the fuzzy logic system was used to calculate the survival risk values of missense variants and classified their membership grade to improve the identification of high-risk gene variation locations associated with cancer mortality. The four models were integrated to develop an advanced risk estimation model. There were 20 028 variants associated with survival status, amongst 17 638 variants were associated with survival and 2390 variants associated with mortality. The proposed Fuzzy-based RNNCoxph model obtained a balanced accuracy of 93.7%, which was significantly higher than that of the other four test methods. In particular, the Coxph model is commonly used in medical researches and the XGBoost model is famous for its high accuracy in machine learning. The results suggest that the Fuzzy-based RNNCoxph model exhibits a higher efficacy

关键词： Fuzzy logic

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Polymethoxyflavone from Citrus depressa as an inhibitor against various variants of SARS-CoV-2 spike protein

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Journal of Ethnopharmacology 2024年 320卷 117412页

作者： Liu, Ta-Wei Hsu, Su-Jung Hsieh, Yves S.Y. Liu, Hui-Kang Lee, Ching-Kuo School of Pharmacy College of Pharmacy Taipei Medical University Taipei 11042 Taiwan Graduate Institute of Pharmacognosy College of Pharmacy Taipei Medical University Taipei 11042 Taiwan Division of Glycoscience Department of Chemistry School of Engineering Sciences in Chemistry Biotechnology and Health KTH Royal Institute of Technology AlbaNova University Centre Stockholm SE106 91 Sweden National Research Institute of Chinese Medicine (NRICM) Ministry of Health and Welfare Taipei City Taiwan Ph. D. Program in the Clinical Drug Development of Herbal Medicine Taipei Medical University Taipei Taiwan

Ethnopharmacological relevance: In traditional Taiwanese medicine, Citrus depressa Hayata serves as the raw material of Chen-Pi which has been widely used to treat respiratory ailments. Scientific investigations have validated the attributes of C. depressa, elucidating its valuable properties, including antioxidative, anti-inflammatory, anticancer, neuroprotion, hepatoprotection, and hypolipidemic effects. Aim of the study: This study aims to isolate a universal inhibitor of the SARS-CoV-2 spike protein from C. depressa and confirm the mechanism by which these inhibitors disrupt the binding of the spike protein to hACE2. Materials and methods: The whole fruit of C. depressa was subjected to ethanol extraction, following by partitioning to obtain water, butanol, and ethyl acetate fractions. To identify the inhibitory components in citrus fruits, we performed both the SPR assay and the SARS-CoV-2 pseudo-virus assays. Subsequently, we employed a bioassay-guided approach to efficiently isolate and characterize the bioactive constituents that hindered the interaction between the SARS-CoV-2 spike protein and hACE2, using a combination of MPLC and Semi-preparative HPLC for compound isolation. ELISA based spike protein binding assay evaluate the inhibitory activities of the extract and potential constituents against multiple spike protein variants. To further shed light on the inhibitory mechanism, candidate inhibitors were validated through the SPR assay and molecular docking. Results: The crude extract and ethyl acetate layer derived from C. depressa showed significant inhibitory activity on SARS-CoV-2 Omicron BA.4/5, with IC₅₀ of 77.4 μg/mL and 100 μg/mL, respectively. Ten potential compounds from C. depressa have been identified with inhibitory activity against various SARS-CoV-2 spike proteins. 2′-hydroxy-4,4′,5′,6′-tetramethoxychalcone (Cd3) and 5-hydroxy-3′,4′,6,7,8-pentamethoxyflavone (Cd8) also showed good inhibitory activity to the spike protein, with K

关键词： ACE-2 Citrus depress Polymethoxyflavone SARS-CoV-2 Spike protein

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Nanomaterials in the treatment and diagnosis of rheumatoid arthritis: Advanced approaches

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SLAS technology 2024年第4期29卷 100146-100146页

作者： Angela, Stefanny Fadhilah, Gianna Hsiao, Wesley Wei-Wen Lin, Hsuan-Yi Ko, Joshua Lu, Steven Che-Wei Lee, Cheng-Chung Chang, Yu-Sheng Lin, Ching-Yu Chang, Huan-Cheng Chiang, Wei-Hung Department of Chemical Engineering National Taiwan University of Science and Technology Taipei Taiwan Department of Power Mechanical Engineering National Tsing Hua University Hsinchu Taiwan Ph.D. Program for Translational Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan Division of Allergy Immunology and Rheumatology Department of Internal Medicine Shuang Ho Hospital New Taipei City Taiwan Division of Allergy Immunology and Rheumatology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan The Ph.D. Program in Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taipei Taiwan School of Medical Laboratory Science and Biotechnology College of Medical Science and Technology Taipei Medical University Taipei Taiwan Department of Chemical Engineering National Taiwan University of Science and Technology Taipei Taiwan Institute of Atomic and Molecular Sciences Academia Sinica Taipei Taiwan Department of Chemistry National Taiwan Normal University Taipei Taiwan Department of Chemical Engineering National Taiwan University of Science and Technology Taipei Taiwan Sustainable Electrochemical Energy Development (SEED) Center National Taiwan University of Science and Technology Taipei Taiwan Advanced Manufacturing Research Center National Taiwan University of Science and Technology Taipei Taiwan. Electronic address: weshsiao@mail.ntust.edu.tw

Rheumatoid arthritis (RA), a chronic inflammatory condition that affects persons between the ages of 20 and 40, causes synovium inflammation, cartilage loss, and joint discomfort as some of its symptoms. diagnostic techniques for RA have traditionally been split into two main categories: imaging and serological tests. However, significant issues are associated with both of these methods. Imaging methods are costly and only helpful in people with obvious symptoms, while serological assays are time-consuming and require specialist knowledge. The drawbacks of these traditional techniques have led to the development of novel diagnostic approaches. The unique properties of nanomaterials make them well-suited as biosensors. Their compact dimensions are frequently cited for their outstanding performance, and their positive impact on the signal-to-noise ratio accounts for their capacity to detect biomarkers at low detection limits, with excellent repeatability and a robust dynamic range. In this review, we discuss the use of nanomaterials in RA theranostics. Scientists have recently synthesized, characterized, and modified nanomaterials and biomarkers commonly used to enhance RA diagnosis and therapy capabilities. We hope to provide scientists with the promising potential that nanomaterials hold for future theranostics and offer suggestions on further improving nanomaterials as biosensors, particularly for detecting autoimmune disorders. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

关键词： Biomarker Biosensor diagnosis Nanomaterials Rheumatoid arthritis Therapy

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Improvement of extracellular polysaccharides production from Cordyceps militaris immobilized alginate beads in repeated-batch fermentation

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LWT 2024年 193卷

作者： Hou, Shi-Jing Cheng, Kuan-Chen Lin, Shyh-Hsiang Hsiao, I-Lun Santoso, Shella Permatasari Singajaya, Stephanie Chou, Yu-Chieh Lin, Shin-Ping Master Program in Food Safety Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan Institute of Biotechnology National Taiwan University 1 Roosevelt Rd. Sec. 4 Taipei10617 Taiwan Graduate Institute of Food Science and Technology National Taiwan University 1 Roosevelt Rd. Sec. 4 Taipei10617 Taiwan Department of Medical Research China Medical University Hospital China Medical University 91 Hsueh-Shih Rd. Taichung40402 Taiwan Department of Optometry Asia University 500 Lioufeng Rd. Wufeng Taichung41354 Taiwan School of Nutrition and Health Sciences Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan School of Food Safety Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan Department of Chemical Engineering Widya Mandala Surabaya Catholic University Kalijudan 37 East Java Surabaya60114 Indonesia Collaborative Research Center for Sustainable and Zero Waste Industries Kalijudan 37 East Java Surabaya60114 Indonesia Ph.D. Program in Drug Discovery and Development Industry Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan Research Center of Biomedical Device Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan TMU Research Center for Digestive Medicine Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan

Cordyceps militaris (C. militaris) is a unique medicinal fungus of the genus Cordyceps. It has high economic value due to various biological functions from the extracellular polysaccharides (EPSs) it produces. The aim of this study was to establish a mycelium-immobilization system for EPS production in a bubble column system. First, EPS production was optimized by 90.2% (from 0.72 to 1.37 g/L) using response surface methodology under an alginate-immobilized mycelium system with 6 days of cultivation. The highest EPS production was obtained (5.3 g/L) in a flask system through elongation to 15 days of cultivation. EPS production subsequently further increased to 10.42 g/L utilizing a bubble column reactor. Furthermore, the system can be reused for at least three rounds. In the EPS characteristics analysis, the produced EPSs were mainly composed of glucose and galactose. They presented strong antibacterial activity against Staphylococcus aureus. In terms of antioxidant activity, respective the EPS concentration that caused 50% scavenging of dPph and ABTS free radicals values (IC50) were 4.65 and 7.92 mg/mL. In summary, these findings should be helpful for establishing a suitable industrial fermentation system for C. militaris and can be studied in the food and medical industries in future work. © 2024 The Authors

关键词： Mycelium

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development of anti-aflatoxin B1 nanobodies from a novel mutagenesis-derived synthetic library for traditional Chinese medicine and foods safety testing

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Journal of biological engineering 2023年第1期17卷 30页

作者： Yu-Ching Lee Gar-Hwa Lai Tsai-Yu Lin Tien-Sheng Tseng Tsung-Hsun Tsai Wang-Chuan Chen Cheng-Chung Lee Keng-Chang Tsai TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei Taiwan. Ph.D. Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Taipei Taiwan. Ph.D. Program in Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Department of Orthopedics Kaohsiung Veterans General Hospital Kaohsiung Taiwan. Institute of Molecular Biology National Chung Hsing University Taichung Taiwan. Department of Psychiatry Kaohsiung Armed Forces General Hospital Kaohsiung Taiwan. The School of Chinese Medicine for Post Baccalaureate I-Shou University Kaohsiung Taiwan. Department of Chinese Medicine E-Da Hospital Kaohsiung Taiwan. The Ph.D. Program for Translational Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Ph.D. Program in Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taipei Taiwan. tkc@nricm.edu.tw. National Research Institute of Chinese Medicine Ministry of Health and Welfare No. 155-1 Sec. 2 Linong St. Beitou District Taipei 11221 Taiwan. tkc@nricm.edu.tw.

BACKGROUNd:The main commercially available methods for detecting small molecules of mycotoxins in traditional Chinese medicine (TCM) and functional foods are enzyme-linked immunosorbent assay and mass spectrometry. Regarding the development of diagnostic antibody reagents, effective methods for the rapid preparation of specific monoclonal antibodies are inadequate. METHOdS:In this study, a novel synthetic phage-displayed nanobody Golden Glove (SynaGG) library with a glove-like cavity configuration was established using phage display technology in synthetic biology. We applied this unique SynaGG library on the small molecule aflatoxin B1 (AFB1), which has strong hepatotoxicity, to isolate specific nanobodies with high affinity for AFB1. RESULT:These nanobodies exhibit no cross-reactivity with the hapten methotrexate, which is recognized by the original antibody template. By binding to AFB1, two nanobodies can neutralize AFB1-induced hepatocyte growth inhibition. Using molecular docking, we found that the unique non-hypervariable complementarity-determining region 4 (CdR4) loop region of the nanobody was involved in the interaction with AFB1. Specifically, the CdR4's positively charged amino acid arginine directed the binding interaction between the nanobody and AFB1. We then rationally optimized the interaction between AFB1 and the nanobody by mutating serine at position 2 into valine. The binding affinity of the nanobody to AFB1 was effectively improved, and this result supported the use of molecular structure simulation for antibody optimization. CONCLUSION:In summary, this study revealed that the novel SynaGG library, which was constructed through computer-aided design, can be used to isolate nanobodies that specifically bind to small molecules. The results of this study could facilitate the development of nanobody materials to detect small molecules for the rapid screening of TCM materials and foods in the future.

关键词： Aflatoxin B1 Glove-like cavity Nanobody Nonhypervariable complementarity-determining region 4 loop phage display technology

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Evaluating the antiviral efficacy and specificity of chlorogenic acid and related herbal extracts against SARS-CoV-2 variants via spike protein binding intervention

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Journal of Traditional and Complementary Medicine 2024年

作者： Hsieh, Wen-Yu Yu, Chu-Nien Chen, Chang-Chang Chiou, Chun-Tang Green, Brian d. Lee, Oscar K. Wu, Chia-Chune doan, Ly Hien Huang, Chi-Ying F. Huang, Cheng Liu, Chien-Ju Chen, Yu-Hsin Cheng, Jing-Jy Pan, Heng-Chih Liu, Hui-Kang Biomedical Industry Ph.D. Program National Yang Ming Chiao Tung University Taipei 11221 Taiwan Institute of Clinical Medicine National Yang Ming Chiao Tung University Taipei 11221 Taiwan Division of Chinese Materia Medica Development National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei 11221 Taiwan Institute for Global Food Security School of Biological Sciences Queen's University Belfast Belfast BT7 1NN United Kingdom Department of Orthopedics China Medical University Hospital Taichung Taiwan Institute of Biopharmaceutical Sciences College of Pharmaceutical Sciences National Yang Ming Chiao Tung University Taipei 11221 Taiwan Institute of Biotechnology Vietnam Academy of Science and Technology Hanoi Viet Nam Program in Molecular Medicine College of Life Sciences National Yang Ming Chiao Tung University Taipei 11221 Taiwan Taiwan National Graduate Program in Molecular Medicine Academia Sinica National Yang Ming Chiao Tung University Taipei 11221 Taiwan Institute of Clinical Medicine College of Medicine National Yang Ming Chiao Tung Taipei 11221 Taiwan Department of Biotechnology and Laboratory Science in Medicine School of Biomedical Science and Engineering National Yang Ming Chiao Tung Taipei 11221 Taiwan Department of Biochemistry School of Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan Department of Earth and Life Sciences University of Taipei Taipei 11036 Taiwan Tea and Beverage Research Station Ministry of Agriculture Yangmei Township Taoyuan County 326011 Taiwan Taichung District Agricultural Research and Extension Station Ministry of Agriculture Chang-Hwa County 515008 Taiwan Division of Basic Chinese Medicine National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei 11221 Taiwan Department of Nephrology Chang Gung Memorial Hospital Keelung City 204201 Taiwan Ph.D. Program in the Clinical Drug Development of Herbal Medicine Taipei Medical University Taipei

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus infect the respiratory tract through surface proteins, causing similar symptoms. Since the onset of the COVId-19 pandemic, both viruses have posed significant ongoing global health threats. Like the influenza virus, SARS-CoV-2 evolves into variants that can reduce vaccine efficacy. Thus, herbal medicines are being explored as supplementary options to enhance protection against these infections. This study aimed to investigate the therapeutic potential of chlorogenic acid (3-CQA) and related extracts from green coffee beans and Echinacea purpurea against SARS-CoV-2 variants and H1N1 infection. The methods employed included an ELISA-based trimeric spike protein binding assay, viral infection assays, plaque assays, and molecular docking studies. Results showed that 3-CQA blocked spike protein/angiotensin converting enzyme 2 (ACE2) binding for most SARS-CoV-2 variants of concern, except the delta variant. Extracts from Green coffee bean and E. purpurea effectively blocked all variants tested. Additionally, antibodies blocked spike protein binding up to Omicron BA.2. Molecular docking suggested that 3-CQA binding to Omicron BA.1, BA.2, and BA.4, though not to the delta spike protein, may lead to steric hindrance, preventing receptor-binding domain interactions with ACE2. Finally, both 3-CQA and E. purpurea extract showed preventive effects against H1N1 viral infection, though with lower potency compared to SARS-CoV-2. In conclusion, 3-CQA has potential as a phytoconstituent marker for herbs with bioactive properties against SARS-CoV-2 and H1N1 viral infections. © 2024 Center for Food and Biomolecules, National Taiwan University

关键词： Chlorogenic acid COVId-19 Echinacea purpurea Green coffee bean H1N1 influenza virus SARS-CoV-2 variants Spike protein

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Agar-altered foaming bacterial cellulose with carvacrol for active food packaging applications

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Food Packaging and Shelf Life 2024年 42卷

作者： Kusuma, Anita Chandra Chou, Yu-Chieh Hsieh, Chen-Che Santoso, Shella Permatasari Go, Alchris Woo Lin, Hong-Ting Victor Hsiao, I.-Lun Lin, Shin-Ping Master Program in Food Safety Taipei Medical University 250 Wu-Hsing Street Taipei 11031 Taiwan Ph.D. Program in Drug Discovery and Development Industry Taipei Medical University 250 Wu-Hsing Street Taipei 11031 Taiwan Institute of Biotechnology National Taiwan University 1 Roosevelt Rd. Section 4 Taipei 10617 Taiwan Department of Chemical Engineering Widya Mandala Surabaya Catholic University Kalijudan 37 Surabaya 60114 Indonesia Department of Chemical Engineering National Taiwan University of Science and Technology 43 Keelung Road Section 4 Taipei 10607 Taiwan Department of Food Science National Taiwan Ocean University No. 2 Pei-Ning Road Keelung 20224 Taiwan School of Food Safety 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 Research Center of Biomedical Device Taipei Medical University 250 Wu-Hsing Street Taipei 11031 Taiwan

Bacterial cellulose (BC) is a biodegradable nanoscale film produced by microorganisms, which possesses great mechanical properties and biocompatibility. In this study, we produced foaming BC (FBC) utilizing foam medium with different concentrations of agar. In addition, carvacrol was loaded into the agar/FBC to establish active packaging material. Evaluation by characterization tests indicated that agar/FBC provided lower crystallinity (59.8%∼71.4%) and a high swelling ability (94.7%∼97.9%) compared to BC (92.2% and 96.1%). The 1.5% agar/FBC with carvacrol group exhibited the significantly highest antimicrobial properties against Escherichia coli and Staphylococcus aureus. Moreover, release measurements showed that greater agar addition contributed to higher protein and carvacrol release extents out of the film. Finally, a sea bass packaging test indicated that carvacrol with 1.5% agar/FBC presented a higher antimicrobial ability against Shewanella putrefaciens, great inhibition of lipid oxidation (67.5%), and a slower spoilage degree (49.8%) which suggested that agar/FBC with carvacrol has potential for active food packaging. © 2024 Elsevier Ltd

关键词： Agar Bacterial cellulose Carvacrol Foaming bacterial cellulose Food packaging Sea bass

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Effects of Citrus depressa Hayata juice on high-fat diet-induced obesity in HBV transgenic mice

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Heliyon 2024年第2期10卷

作者： Chu, Pei-Yi Hsu, Chang-Lu Lin, Yen-An Pan, Yi-Cheng dai, Yun-Hao Yu, Ying-Chun Yang, Juan-Cheng Ma, Wen-Lung Chen, Yi-Jinn Lillian Lee, Chia-Lin Wu, Yang-Chang Chinese Medicine Research and Development Center China Medical University Hospital Taichung Taiwan Department of Business Administration National Chiayi University Chiayi Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan .Ph.D. Program for Cancer Biology and Drug Discovery China Medical University and Academia Sinica Taichung Taiwan School of Pharmacy China Medical University Taichung Taiwan Department of Medical Research and Organ Transplantation Center China Medical University Hospital Taichung Taiwan School of Chinese Medicine College of Chinese Medicine China Medical University Taichung Taiwan Department of Physics National Kaohsiung Normal University Kaohsiung Taiwan Department of Cosmeceutics China Medical University Taichung 40604 Taiwan Graduate Institute of Integrated Medicine College of Chinese Medicine China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology College of Medical and Health Science Asia University Taichung Taiwan

The present study investigated the potential anti-obesity properties of Citrus depressa Hayata (CdH) juice in HBV transgenic mice, as well as the impact of fermentation on the effectiveness of the juice. The results revealed that fermentation increased the levels of polyphenols and hesperidin in CdH juice. The animal study demonstrated that both juices were effective in mitigating the weight gain induced by a high-fat diet by correcting metabolic parameter imbalances, reducing hepatic lipid accumulation, and reversing hepatic immune suppression. Furthermore, fermented juice exhibited superior efficacy in managing body weight and inhibiting the expansion of white adipose tissue (WAT). Fermented juice significantly enhanced adiponectin production and PPARγ expression in WAT, while also reducing hypertrophy. This study offers valuable insights into the potential role of CdH juices in combating obesity associated with high fat consumption and underscores the promise of CdH juice as a functional beverage. © 2024 The Authors

关键词： Citrus depressa hayata fermentation HBV Hesperidin High-fat diet-induced obesity Juice Mice Polyphenol

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Creatine and l-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish

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Scientific Reports 2024年第1期14卷 1-19页

作者： Pan, Shao-Wei Wang, Horng-dar Hsiao, He-Yun Hsu, Po-Jui Tseng, Yung-Che Liang, Wen-Chen Jong, Yuh-Jyh Yuh, Chiou-Hwa Institute of Molecular and Genomic Medicine National Health Research Institutes Miaoli Zhunan Taiwan Institute of Biotechnology National Tsing Hua University Hsinchu Taiwan Department of Laboratory Medicine Mackay Memorial Hospital Taipei Taiwan Department of Medical Laboratory Science and Biotechnology Yuanpei University of Medical Technology Hsinchu Taiwan Department of Nursing MacKay Medical College Taipei Taiwan Marine Research Station Institute of Cellular and Organism Biology Academia Sinica I-Lan Taiwan Department of Pediatrics School of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Graduate Institute of Clinical Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Pediatrics Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Translational Research Center of Neuromuscular Diseases Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Department of Laboratory Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu Taiwan Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu Taiwan Ph.D. Program in Environmental and Occupational Medicine Kaohsiung Medical University Kaohsiung Taiwan

Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by danioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify l-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathw

关键词： Creatine l-Carnitine LMNA Striated muscle laminopathy Zebrafish

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