检索结果-内蒙古大学图书馆

Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity

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Nanomedicine: Nanotechnology, Biology, and Medicine 2023年 47卷 102628-102628页

作者： Chen, Chia-Hung Weng, Tzu-Han Chuang, Cheng-Hsun Huang, Kai-Yao Huang, Sih-Cheng Chen, Pin-Rong Huang, Hsiao-Hsuan Huang, Ling-Ya Shen, Pei-Chun Chuang, Po-Ya Huang, Hsiao-Yen Wu, Yi-Syuan Chang, Hao-Chiun Weng, Shun-Long Liao, Kuang-Wen Department of Medical Research Hsinchu MacKay Memorial Hospital Hsinchu City30071 Taiwan Dependent of Medical Education MacKay Memorial Hospital Taipei10449 Taiwan Institute of Molecular Medicine and Bioengineering National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Industrial Development Graduate Program of College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Medicine MacKay Medical College New Taipei City25245 Taiwan Department of Obstetrics and Gynecology Hsinchu MacKay Memorial Hospital Hsinchu City30071 Taiwan MacKay Junior College of Medicine Nursing and Management Taipei City11260 Taiwan Drug Development and Value Creation Research Center College of Dental Medicine Kaohsiung Medical University School of Dentistry Graduate Institute of Medicine College of Medicine Center for Cancer Research Kaohsiung Medical University Kaohsiung City80708 Taiwan Center for Intelligent Drug Systems and Smart Bio-devices National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Biotechnology and Bioindustry Sciences National Cheng Kung University Tainan City70101 Taiwan Ph.D. Degree Program of Biomedical Science and Engineering National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (dOX) and carrying CpG oligodeoxynucleotide;the transdermally administered nano-liposomal drug complex (LPPC-dOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-dOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-dOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-dOX-CpG. Finally, we have successfully proved transdermal LPPC-dOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor. © 2022

关键词： Tumors

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Size-controlled immunomodulatory and vaccine adjuvant potentials of self-assembled hyaluronic acid nanoparticles: Activation and recruitment of immune cells

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International Journal of Biological Macromolecules 2025年 314卷 144265页

作者： Chu, Po-Cheng Birhan, Yihenew Simegniew Zhao, Min-Han Syu, Wei-Jhe Chen, Po-Yen Lin, Yu-Tsen Lai, Ping-Shan Department of Chemistry National Chung Hsing University Taichung402 Taiwan Basic Research and Development Department Powin Biomedical Co. Ltd. Taichung428 Taiwan Department of Chemistry College of Natural and Computational Sciences Debre Markos University P.O. Box 269 Debre Markos Ethiopia Department of Chemical and Biomolecular Engineering University of Maryland College Park MD20742 United States Ph.D. Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung402 Taiwan

Immunotherapy has paramount importance in treating chronic immune diseases, and vaccine development. Hyaluronic acid (HA) has been shown to elicit molecular weight-related distinct immune responses. Nonetheless, the particle size-dependent immunomodulatory effects of hyaluronic acid nanoparticles (HA-NPs) remain blurred. Thus, the present study aimed at investigating the effect of polymer configuration and particle size of HA-NPs assembled from HA36K-OdA and HA360k-OdA analogs in modulating macrophage-related immune activities. In the in vitro experiments, HA-NPs of HA36k-OdA analogs garnered significantly enhanced nitrite production with low interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) secretion in macrophages. Furthermore, smaller (36k-OdA NPs activated Cd11b+ cells whereas a ∼ 130 nm HA36k-OdA15 NPs preferentially induced Cd11c+ cells in vivo, indicating the influence of particle size on the antigen-presenting cells (APCs) recruitment. Interestingly, self-assembled HA36k-OdA15 NPs without ovalbumin (OVA) activated immature dendritic cells (dCs) and augmented their migration toward the lymph nodes (LNs). Notably, HA36k-OdA15-activated macrophages behaved like M1 phenotype macrophages. Overall, our findings garnered valuable insights about the design and application of HA-NPs for modulating the immune responses in nanoscale materials-based immunotherapy. © 2025

关键词： Macrophages

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Toxoplasma gondii infection in small ruminants from Khyber Pakhtunkhwa, Pakistan: Seroprevalence, spatial distribution and associated risk factors

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Veterinary Parasitology: Regional Studies and Reports 2024年 47卷 100979页

作者： Khattak, Irfan Usman, Tahir Swelum, Ayman A. Nasreen, Nasreen Khan, Adil Haider, Jamila Muhammad, Javed Chen, Chien-Chin Ben Said, Mourad College of Veterinary and Animal Husbandry Abdul Wali Khan University Mardan Khyber Pakhtunkhwa Pakistan Department of Animal Production College of Food and Agriculture Sciences King Saud University Riyadh 11451 Saudi Arabia Department of Zoology Khyber Pakhtunkhwa Abdul Wali Khan University Mardan 2320 Pakistan Department of Zoology Khyber Pakhtunkhwa Bacha Khan University Charsadda Pakistan Department of Biology Mount Allison University Sackville E4L1E4 NB Canada Department of Microbiology Shaheed Benazir Women University Peshawar Khyber Pakhtunkhwa Pakistan Department of Microbiology University of Haripur Khyber Pakhtunkhwa Pakistan 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 Ph.D. Program in Translational Medicine Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung 402 Taiwan Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan 701 Taiwan Laboratory of Microbiology National School of Veterinary Medicine of Sidi Thabet University of Manouba Manouba 2010 Tunisia Department of Basic Sciences Higher Institute of Biotechnology of Sidi Thabet University of Manouba Manouba 2010 Tunisia

The primary aim of this investigation was to assess the occurrence of Toxoplasma gondii infection among sheep and goats in five districts within the southern region of Khyber Pakhtunkhwa province, Pakistan. Additionally, the study aimed to pinpoint potential factors associated with the spread of this infection. Serum samples were gathered from a total of 3505 small ruminants, comprising 1810 sheep and 1695 goats. These samples were then subjected to testing for anti-Toxoplasma antibodies using the Toxo-Latex slide Agglutination test. Concurrently, a predetermined questionnaire was employed to gather data on possible risk factors. The collected data underwent bivariate frequency analysis and multivariable logistic regression analyses. The findings revealed that 20.08% of the examined animals had positive results for anti-Toxoplasma antibodies. Notably, the prevalence of T. gondii was notably higher among sheep, with 21.8% of the sheep testing positive, as opposed to the 18% of tested goats (P = 0.007). The seroprevalence percentages were comparable across the five districts for both types of animals. For goats, the prevalence ranged from 16.8% to 20.1%, while for sheep, it ranged from 20.2% to 24%. Among the younger population (≤1 year), the seroprevalence was statistically lower at 17.7% compared to the older population (>1 year) at 23.1% (P < 0.001). Female animals demonstrated a higher prevalence (21.9%) in contrast to their male counterparts (17.8%) (P = 0.002). Animals reared for breeding and milking purposes displayed a greater seroprevalence (23.9%) compared to those intended for sale (17.7%) (P < 0.001). Furthermore, animals kept under a transhumant production system displayed the lowest prevalence (18.9%), followed by sedentary (21.7%) and nomadic (31.2%) herds (P < 0.001). The outcomes of this study highlight the importance of implementing management interventions to curtail T. gondii infection among animals within the Khyber Pakhtunkhwa province of Pakista

关键词： Epidemiological investigation Pakistan Risk factors Seroprevalence Small ruminants Toxoplasma gondii

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The biocompatibility and hemostatic efficacy of silk fibroin nanofibrils fabricated by Shear-Induced phase separation process

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Chemical Engineering Journal 2023年 474卷

作者： Lu, Po-Wen Wu, Yu-Tzu Chang, Liang-Yu Lu, Tzu-Wei Jaihao, Chonlachat Huang, Ching-Shuan Murphy Chuang, Mo-Fei Lin, Chunche Chen, Innie Brangule, Agnese Zarkov, Aleksej Kareiva, Aivaras Yang, Jen-Chang Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei11052 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine Shuang Ho Hospital Taipei Medical University Zhongzheng Rd. Taipei Zhonghe23561 Taiwan Graduate Institute of Nanomedicine and Medical Engineering College of Biomedical Engineering Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan Department of Dentistry Taipei Medical University Hospital Taipei11031 Taiwan Institute of Organic and Polymeric Materials National Taipei University of Technology Taipei106344 Taiwan Research and Development Center for Smart Textile Technology National Taipei University of Technology Taipei106344 Taiwan Innie Chen Department of Obstetrics and Gynecology University of Ottawa OttawaONK1H 7W9 Canada Department of Pharmaceutical Chemistry Riga Stradins University RīgaLV-1007 Latvia Institute of Chemistry Vilnius University Naugarduko 24 VilniusLT-03225 Lithuania International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Research Center of Biomedical Device Taipei Medical University Taipei11031 Taiwan Research Center of Digital Oral Science and Technology Taipei Medical University Taipei11031 Taiwan

The objectives of this study were to investigate the biocompatibility and hemostatic efficacy of silk fibroin nanofibrils (SFNFs). Unlike a conventional dialysis/freeze-drying process, SFNFs were prepared using a novel shear-induced phase-separation method. The morphology, particle size distribution, protein secondary structures, and crystalline structures of the resulting SFNFs were respectively investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), laser diffraction (Ld), Fourier-transform infrared (FTIR) spectroscopy, and x-ray diffraction (XRd) deconvolution analyses. Polar and non-polar extractants of SFNFs under a bath ratio of 0.2 g/mL were collected after individually soaking them into 0.9% normal saline and cottonseed oil. In vitro hemolysis ratios, biocompatibility, and sensitization tests were carried out. Then, the hemostatic efficacy was assayed using a rat liver punch biopsy model. Compared to dialyzed/freeze-dried SF, the harvested SFNFs revealed high surface area in morphology. The median particle size distribution, d50, was 294 μm for SFNFs. Shear-induced hydrogen bonding, crystallization, and phase separation tended to give the SFNFs a high crystalline index (CI) and degree of crystallinity (dC). The hemolysis ratio of SFNFs was 0.86 ± 0.40%, and it was classified as being non-hemolytic (0%∼2%). The test results of toxicity and skin sensitization were both negative. The hemostasis time for SFNFs (2.8 ± 0.6 min) was statistically less than that of oxidized cellulose (4.3 ± 0.9 min) (p © 2023 Elsevier B.V.

关键词： Biocompatibility

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SRT1720 as an SIRT1 Activator for Alleviating Paraquat-Induced Models of Parkinson's disease

SSRN

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SSRN 2022年

作者： Chao, Chih-Chang Huang, Chuen-Lin Cheng, Jing-Jy Chiou, Chun-Tang Lee, I-Jung Yang, Ying-Chen Hsu, Ting-Huang Yei, Chan Lin, Pei-Yin Cheng, Jih-Jung Huang, Nai-Kuei Institute of Neuroscience National Chengchi University Taipei Taiwan Medical Research Center Cardinal Tien Hospital Hsintien New Taipei City Taiwan Graduate Institute of Physiology Department of Physiology and Biophysics National Defense Medical Center Taipei114 Taiwan National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei112 Taiwan Institute of Biophotonics National Yang-Ming University Taipei112 Taiwan Herbal Medicine Department Yokohama University of Pharmacy Yokohama Japan Department of Biotechnology and Animal Science National Ilan University Ilan Taiwan School of Pharmaceutical Sciences National Yang-Ming Chiao Tung University Taipei Taiwan Ph.D. Program for Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei11031 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan

Epidemiological studies have linked herbicides and Parkinson’s disease (Pd), with the strongest associations resulting from long exposure durations. Paraquat (PQ), an herbicide, induces Pd-like syndromes and has widely been accepted as a Pd mimetic. Currently, there is still no cure to prevent the progression of Pd, and the search for effective therapeutic ways is urgent. Recently, the impairing activity of sirtuins (SIRTs), such as SIRT1, may correlate with Pd etiology. However, the nonspecificity of SIRT1 agonists has made the protective mechanisms against Pd unclear and hampered the therapeutic application of SIRT1. Thus, this study investigated the protective mechanism and therapeutic potential of SRT1720, a more specific agonist for SIRT1, in alleviating the toxicity of PQ-induced cellular and animal models of Pd. Here we show that SRT1720 alleviates PQ-induced toxicity in cell and animal models. Genetic silencing and pharmacological inhibition of SIRT1 attenuated SRT1720’s protection against PQ-induced toxicity. Moreover, SRT1720 not only attenuated PQ-induced increased oxidative stress and mitochondrial free radical formations but also decreased mitochondrial membrane potential. Furthermore, SRT1720 reversed PQ-induced decreased PGC-1α levels and mitochondrial biogenesis. Although PQ and SRT1720 elevated NRF2 and antioxidative enzyme levels, only PQ decreased antioxidative enzyme activity but not SRT1720. NRF2 and PGC-1α silencing attenuated SRT1720 protection against PQ-induced toxicity. SRT1720 targeted SIRT1 and activated downstream PGC-1a and NRF2 signalings to prevent PQ-induced toxicity involving oxidative stress and mitochondrial dysfunction. Thus, SRT1720 might have therapeutic potential in preventing Pd. © 2022, The Authors. All rights reserved.

关键词： Mitochondria

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Correction to: Biological synthesis and characterization of iron oxide (FeO) nanoparticles using Pleurotus citrinopileatus extract and its biomedical applications

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Biomass Conversion and Biorefinery 2023年第11期14卷 12587-12587页

作者： Manimaran, Kumar Yanto, dede Heri Yuli Govindasamy, Mani Karunanithi, Bogeshwaran Alasmary, Fatmah Ali Habab, Reem Abdulrahman Research Center for Applied Microbiology National Research and Innovation Agency (BRIN) Cibinong Republic of Indonesia Department of Product Development Institute of Biotechnology Saveetha School of Engineering Saveetha Institute of Medical and Technical Sciences (SIMATS) Chennai India Faculty International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City Taiwan Korea University Seongbuk-gu Republic of Korea Department of Research and Innovation Saveetha School of Engineering SIMATS Thandalam India Department of Petroleum Engineering Dhaanish Ahmed College of Engineering Chennai India Department of Chemistry College of Science King Saud University Riyadh Saudi Arabia

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Enhanced exopolysaccharide production of Cordyceps militaris via mycelial cell immobilization on plastic composite support in repeated-batch fermentation

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International Journal of Biological Macromolecules 2023年第1期250卷 126267页

作者： Lin, Shin-Ping Sung, Ting-Hsuan Angkawijaya, Artik Elisa Go, Alchris Woo Hsieh, Chang-Wei Hsu, Hsien-Yi Santoso, Shella Permatasari Cheng, Kuan-Chen School of Food Safety Taipei Medical University #250 Wuxing Street Xinyi Dist. Taipei11042 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 Ph.D. Program in Drug Discovery and Development Industry Taipei Medical University #250 Wu-Hsing Street Taipei11031 Taiwan Taiwan Institute of Food Science and Technology National Taiwan University #1 Sec. 4 Roosevelt Rd. Taipei10617 Taiwan Institute of Food Science and Technology National Taiwan University #1 Sec. 4 Roosevelt Rd. Taipei10617 Taiwan School of Nutrition and Health Sciences Taipei Medical University #250 Wu-Hsing Street Taipei11031 Taiwan Center for Sustainable Resource Science RIKEN Yokohama230-0045 Japan Department of Chemical Engineering National Taiwan University of Science and Technology #43 Sec. 4 Keelung Rd Taipei10607 Taiwan Department of Food Science and Biotechnology National Chung Hsing University South Dist. Taichung City40227 Taiwan Department of Medical Research China Medical University Hospital North Dist. Taichung City404333 Taiwan Taiwan Institute of Biotechnology National Taiwan University #1 Sec. 4 Roosevelt Rd. Taipei10617 Taiwan School of Energy and Environment Department of Materials Science and Engineering City University of Hong Kong Kowloon Tong Hong Kong Shenzhen Research Institute of City University of Hong Kong Shenzhen518057 China Department of Chemical Engineering Widya Mandala Surabaya Catholic University Kalijudan 37 Surabaya60114 Indonesia Collaborative Research Center for Zero Waste and Sustainability Jl. Kalijudan 37 East Java Surabaya60114 Indonesia Institute of Biotechnology National Taiwan University #1 Sec. 4 Roosevelt Rd. Taipei10617 Taiwan Department of Medical Research China Medical University Hospital China Medical University 91 Hsueh-Shih Road Taichung40

Repeated-batch fermentation with fungal mycelia immobilized in plastic composite support (PCS) eliminates the lag phase during fermentation and improves metabolite productivity. The strategy is implemented herein, and a novel modified PCS is developed to enhance exopolysaccharide (EPS) production from the medicinal fungus Cordyceps militaris. A modified PCS (SYE + PCS) was made by compositing polypropylene (PP) with a nutrient mixture containing soybean hull, peptone, yeast extract, and minerals (SYE+). The use of SYE + PCS has consistent cell productivity throughout the multiple fermentation cycles, which resulted in a more higher cell productivity after second batch compared to unmodified PCS. The cell grown on SYE + PCS also generates a higher yield of EPS (3.36, 6.93, and 5.72 g/L in the first, second, and third fermentation cycles, respectively) up to three-fold higher than the cell immobilized on unmodified PCS. It is also worth noting that the EPS from mycelium grown on SYE + PCS contains up to 2.3-fold higher cordycepin than those on unmodified PCS. The presence of nutrients in SYE + PCS also affects the hydrophobicity and surface roughness of the PC, improving mycelial cell adhesion. This study also provides a preliminary antioxidant activity assessment of EPS from immobilized C. militaris grown with SYE + PCS. © 2023

关键词： Mycelium

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Computer-aided drug discovery of a dual-target inhibitor for ovarian cancer: therapeutic intervention targeting CdK1/TTK signaling pathway and structural insights in the NCI-60

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Computers in biology and medicine 2025年 193卷 110445页

作者： Sung-Ling Tang Maryam Rachmawati Sumitra Yu-Cheng Kuo Han-Lin Hsu Muhamad Ansar Sheng-Liang Huang Shih-Yu Lee Hong-Jaan Wang Bashir Lawal Alexander T H Wu Lung-Ching Chen Hsu-Shan Huang School of Pharmacy National Defense Medical Center Taipei 11490 Taiwan. PhD Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei 11031 Taiwan Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei 11031 Taiwan. Department of Pharmacology School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan School of Post-Baccalaureate Chinese Medicine College of Chinese Medicine China Medical University Taichung 40604 Taiwan. Graduate Institute of Clinical Medicine Taipei Medical University Taipei 11031 Taiwan Division of Pulmonary Medicine Department of Internal Medicine Wanfang Hospital Taipei Medical University Taipei 11031 Taiwan. Ph.D. Program in the Clinical Drug Development of Herbal Medicine Taipei Medical University Taipei 110301 Taiwan. Graduate Institute of Aerospace and Undersea Medicine National Defense Medical Center Taipei 11490 Taiwan. UPMC Hillman Cancer Center University of Pittsburgh Pittsburgh PA USA. Ph.D. Program of Translational Medicine College of Science and Technology Taipei Medical University Taipei 11031 Taiwan. Division of Cardiology Department of Internal Medicine Shin Kong Wu Ho-Su Memorial Hospital Taipei 11101 Taiwan. School of Pharmacy National Defense Medical Center Taipei 11490 Taiwan Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei 11031 Taiwan Ph.D. Program in Biotechnology Research and Development College of Pharmacy Taipei Medical University Taipei 11031 Taiwan. Electronic address: huanghs99@tmu.edu.tw.

Ovarian cancer remains the third most prevalent and deadliest gynecologic malignancy worldwide, with most patients eventually developing resistance to platinum-based chemotherapy. This highlights a critical unmet need for innovative multitargeted therapies to address current treatment challenges. In this study, we identified 35 differentially expressed genes (dEGs) through integrated analysis of four GEO ovarian cancer datasets, with validation using TCGA data. Gene Ontology (GO) and KEGG enrichment analyses highlighted key tumor-associated pathways, and protein-protein interaction (PPI) network modeling prioritized CdK1 and TTK as high-value therapeutic targets. We evaluated the association between molecular genomic features and drug responses across the NCI-60 ovarian cancer cell line panel (IGROV1, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, NCI/AdR-RES, and SK-OV-3), using a series of salicylanilide-derived compounds and four FdA-approved drugs (cabozantinib, paclitaxel, rapamycin, and niclosamide) from the NCI developmental Therapeutics program (dTP). Among these, NSC765690 (MCC22) emerged as the most promising candidate. It demonstrated potent antiproliferative activity, high target selectivity, and strong binding affinity to both CdK1 and TTK. Multi-omics integration, combined with AI-driven network modeling, further elucidated NSC765690's mechanism of action and its relevance to ovarian cancer pathogenesis. Additionally, AdMET and pharmacokinetic profiling confirmed its favorable drug-like properties and low predicted toxicity. Collectively, these findings establish NSC765690 as a potent dual-target inhibitor and exemplify a rational, data-driven drug discovery pipeline for overcoming chemotherapy resistance in ovarian cancer.

关键词： dual-target small molecule inhibitor Machine learning Molecular docking Molecular dynamics simulations NCI-60 panel Ovarian cancer

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Application of bioactive molecular networking to identify corneal-cytoprotective compounds from dialium cochinchinense Pierre. leaves

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Current Plant Biology 2025年 42卷

作者： Nguyen, Thi Tuyet Nhung Lin, Yu-Chi Nguyen, Le-Anh-Tuan Chao, Chih-Hua Vo, Thanh-Hoa Hsu, Su-Jung Tsai, Keng-Chang Lee, Ching-Kuo Cheng, Jing-Jy Ph.D. Program in Clinical Drug Development of Herbal Medicine College of Pharmacy Taipei Medical University Taipei 11031 Taiwan National Research Institute of Chinese Medicine Taipei 11221 Taiwan Faculty of Pharmacy Lac Hong University Dong Nai 810000 Viet Nam School of Pharmacy China Medical University Taichung 404328 Taiwan Chinese Medicine Research and Development Center China Medical University Hospital Taichung 404327 Taiwan University of Health Sciences Vietnam National University Ho Chi Minh City Ho Chi Minh City 700000 Viet Nam Institute of Fisheries Science National Taiwan University Taipei 106 Taiwan Center for Discovery and Development of Healthcare Product Vietnam National University Ho Chi Minh City Ho Chi Minh 700000 Viet Nam

dry eye disease (dEd) requires innovative therapeutic strategies targeting inflammation and oxidative stress. In this study, we demonstrate for the first time that dialium cochinchinense leaf extracts exhibited significant anti-inflammatory activities by inhibiting the nuclear transcription factor-κB (NF-κB) signaling pathway in macrophages. Additionally, these extracts showed notable antioxidant and cytoprotective capabilities, effectively mitigating oxidative stress-induced damage in corneal epithelial cells. We employed an advanced bioactive molecular networking strategy to prioritize and isolate key bioactive compounds, providing distinct advantages over traditional phytochemical screening methods. This approach led to the discovery of a new compound, 6S,9R-2′-O-sinapoyl-roseoside, and 11 known phenolic compounds. Notably, 10 of these compounds exhibited substantial corneal-cytoprotective effects in vitro. Network pharmacology analysis revealed 65 key shared targets between these compounds and dEd, linked to PI3K/AKT and MAPK pathways critical for inflammation and cell survival. Subsequent molecular docking and molecular dynamics simulations confirmed stable and high-affinity binding interactions between the identified lead compounds and key protein targets implicated in dEd. These findings demonstrate d. cochinchinense leaf extract and its bioactive constituents are promising natural candidates for dEd, providing a scientific basis for further translational research and potential drug development. © 2025 The Authors

关键词： Bioactive molecular networking Cytoprotective effect dialium cochinchinense dry eye disease Molecular dynamics simulations Network pharmacology

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Targeting the Neuropilin-1 receptor with Ovatodiolide and progress in using periodontal ligament organoids for COVId-19 research and therapy

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Life Sciences 2024年 351卷 122764页

作者： Hsieh, Ming-Shou Chen, Ming-Yao Chang, Yu-Sheng Huang, Chin-Sheng Hsu, Tung-Nien Huang, Mao-Suan Yeh, Chi-Tai Tzeng, Yew-Min Department of Otolaryngology School of Medicine College of Medicine Taipei Medical University Taipei City 11031 Taiwan Department of Otolaryngology-Head and Neck Surgery Shuang Ho Hospital Taipei Medical University New Taipei City 23561 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei City 110 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine Taipei Medical University-Shuang Ho Hospital New Taipei City 235 Taiwan Division of Allergy Immunology and Rheumatology Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City 23561 Taiwan Division of Allergy Immunology and Rheumatology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Department of Medical Research & Education Taipei Medical University-Shuang Ho Hospital New Taipei City 23561 Taiwan International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei City 11031 Taiwan Continuing Education Program of Food Biotechnology Applications College of Science and Engineering National Taitung University Taitung 95092 Taiwan Department of Applied Science National Taitung University Taitung 95092 Taiwan TMU Research Center for Digestive Medicine Taipei Medical University Taipei 110 Taiwan

The discovery of SARS-CoV-2 RNA in the periodontal tissues of patients who tested positive for COVId-19, 24 days post the initial symptom onset, indicates the oral cavity could serve as a viral reservoir. This research aims to investigate the antiviral capabilities of Ovatodiolide, introducing a novel periodontal ligament organoid model for the study of SARS-CoV-2. We have successfully established a reliable and expandable organoid culture from the human periodontal ligament, showcasing characteristics typical of epithelial stem cells. This organoid model enables us to delve into the lesser-known aspects of dental epithelial stem cell biology and their interactions with viruses and oral tissues. We conducted a series of in vitro and ex vivo studies to examine the inhibitory impacts of Ova on SARS-CoV-2. Our findings indicate that Ovatodiolide molecules can bind effectively to the NRP1 active domain. Our study identifies potential interaction sites for Ovatodiolide (OVA) within the b1 domain of the NRP1 receptor. We generated point mutations at this site, resulting in three variants: Y25A, T44A, and a double mutation Y25A/T44A. While these mutations did not alter the binding activity of the spike protein, they did impact the concentration of OVA required for inhibition. The inhibitory concentrations for these variants are 15 μM for Y25A, 15.2 μM for T44A, and 25 μM for the double mutant Y25A/T44A. In addition, in vitro inhibition experiments demonstrate that the EC50 of Ova against the main protease (Mpro) of the SARS-CoV-2 virus is 7.316 μM. Our in vitro studies and the use of the periodontal ligament organoid model highlight Ovatodiolide's potential as a small molecule therapeutic agent that impedes the virus's ability to bind to the Neuropilin-1 receptor on host cells. The research uncovers various pathways and biochemical strategies through which Ovatodiolide may function as an effective antiviral small molecule drug. © 2024 Elsevier Inc.

关键词： Human Neuropilin-1 Main protease Ovatodiolide Periodontal ligament organoids SARS-CoV-2

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