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Plant-derived galactolipids enhance specific antibody production and induce class-switch as vaccine adjuvant

Vaccine 2024年第4期42卷 782-794页

作者： Lin, Han-Huei Wu, Yi-Shin Chang, Meng-Ting Shyur, Lie-Fen Lin, Yu-Ling Agricultural Biotechnology Research Center Academia Sinica Taipei Taiwan Ph.D. Program in Translational Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Institute of BioPharmaceutical Sciences National Sun Yat-sen University Kaohsiung Taiwan

Various plant-derived compounds can activate immune responses against bacterial infections, and this property contributes to them being developed as effective and safe adjuvants for vaccines. This study evaluated the potential adjuvant effects of a galactolipid-enriched fraction generated from the medicinal plant Crassocephalum rabens (designated CRA). Heat shock protein 60 of periodontal disease pathogen Actinobacillus actinomycetemcomitans (AaHSP60) was taken as an antigen and mixed with CRA. The AaHSP60/CRA mixture was then injected intraperitoneally into the BALB/c mice. Titers and affinity of specific antibodies were measured by ELISA. Cytokine profiles in mouse serum or culture media of AaHSP60/CRA-treated splenocytes were analyzed by cytokine multiplex assay and ELISA kits. B cell differentiation and macrophage activation were determined by phenotyping. CRA dramatically enhanced specific antibody titers and induced Ig class switch, as shown by increases in the IgG2a, IgG2b, and IgG3 proportions of total Ig in mouse serum. Furthermore, CRA-induced anti-AaHSP60 antibodies had cross-reactivity to other bacterial HSP60s. Cell-based and animal results demonstrated that CRA induced the release of IL-21 and B cell activating factor (BAFF), which stimulated B cell differentiation. CRA enhanced cell proliferation, uptake ability, and antigen presentation in mouse phagocytes. CRA served as a vaccine adjuvant that enhance mouse immunity against pathogenic antigens. CRA strengthened the activation and capabilities of phagocytes and B cells. Therefore, CRA may be a promising adjuvant for bacterial vaccines including periodontal disease. © 2024 Elsevier Ltd

关键词： BAFF Galactolipid Humoral immunity IL-21 Plant-derived adjuvant

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7S,8R-dihydroxydeepoxysarcophytoxide: A natural dihydrofuranocembranoid from the octocoral Sarcophyton stellatum

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phytochemistry Letters 2024年 63卷 14-17页

作者： Sheu, Jyh-Horng Zheng, Li-Guo Chen, You-Ying Chien, Su-Ying Sung, Ping-Jyun Department of Marine Biotechnology and Resources National Sun Yat-sen University Chinese Medicine Research and Development Center China Medical University Hospital National Museum of Marine Biology and Aquarium Instrumentation Center National Taiwan University Graduate Institute of Natural Products Kaohsiung Medical University Ph.D. Program in Pharmaceutical Biotechnology Fu Jen Catholic University

Chemical screening of the octocoral Sarcophyton stellatum led to the isolation of a natural dihydrofuranocembranoid, 7S,8R-dihydroxydeepoxysarcophytoxide (1). Single-crystal X-ray diffraction analysis was conducted to determine the absolute configuration of 1, and its structure was confirm using two-dimensional NMR experiments and a literature review. dihydrofuranocembranoid 1 actively enhanced alkaline phosphatase activity. © 2024 phytochemical Society of Europe

关键词： Absolute configuration Alkaline phosphatase dihydrofuranocembranoid Sarcophytoxide

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Structure-guided identification and characterization of potent inhibitors targeting phoP and MtrA to combat mycobacteria

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Computational and Structural biotechnology Journal 2024年 23卷 1477-1488页

作者： Su, Han-Li Lai, Shu-Jung Tsai, Keng-Chang Fung, Kit-Man Lung, Tse-Lin Hsu, Hsing-Mien Wu, Yi-Chen Liu, Ching-Hui Lai, Hui-Xiang Lin, Jiun-Han Tseng, Tien-Sheng Department of Emergency Medicine Ditmanson Medical Foundation Chia-Yi Christian Hospital Chiayi City600 Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Research Center for Cancer Biology China Medical University Taichung Taiwan National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei Taiwan Ph.D. Program in Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taipei Taiwan Academia Sinica Taipei11529 Taiwan Institute of Molecular Biology National Chung Hsing University Taichung Taiwan Department of Industrial Technology Ministry of Economic Affairs Taipei Taiwan Food Industry Research and Development Institute Hsinchu City Taiwan

Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. drug-resistant TB strains are rapidly emerging, thereby necessitating the urgent development of new drugs. Two-component signal transduction systems (TCSs) are signaling pathways involved in the regulation of various bacterial behaviors and responses to environmental stimuli. Applying specific inhibitors of TCSs can disrupt bacterial signaling, growth, and virulence, and can help combat drug-resistant TB. We conducted a comprehensive pharmacophore-based inhibitor screening and biochemical and biophysical examinations to identify, characterize, and validate potential inhibitors targeting the response regulators phoP and MtrA of mycobacteria. The constructed pharmacophore model phar-PR-n4 identified effective inhibitors of formation of the phoP–dNA complex: ST132 (IC50 = 29 ± 1.6 µM) and ST166 (IC50 = 18 ± 1.3 µM). ST166 (Kd = 18.4 ± 4.3 μM) and ST132 (Kd = 14.5 ± 0.1 μM) strongly targeted phoP in a slow-on, slow-off manner. The inhibitory potency and binding affinity of ST166 and ST132 for MtrAC were comparable to those of phoP. Structural analyses and molecular dynamics simulations revealed that ST166 and ST132 mainly interact with the α8-helix and C-terminal β-hairpin of phoP, with functionally essential residue hotspots for structure-based inhibitor optimization. Moreover, ST166 has in vitro antibacterial activity against Macrobacterium marinum. Thus, ST166, with its characteristic 1,2,5,6-tetrathiocane and terminal sulphonic groups, has excellent potential as a candidate for the development of novel antimicrobial agents to combat pathogenic mycobacteria. © 2024 The Authors

关键词： Antimicrobial agents

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deep-Learning Approach for An Analysis of Real-estate Prices and Transactions

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IEEE Access 2025年 13卷 89248-89265页

作者： Yang, Cheng-Hong Lee, Borcy Lin, Yu-da Tainan University of Technology Department of Information Management Tainan Taiwan National Kaohsiung University of Science and Technology Department of Electronic Engineering Kaohsiung Taiwan Kaohsiung Medical University Ph.D. Program in Biomedical Engineering Kaohsiung Taiwan Kaohsiung Medical University School of Dentistry Kaohsiung Taiwan Kaohsiung Medical University Drug Development and Value Creation Research Center Kaohsiung Taiwan National Penghu University of Science and Technology Department of Computer Science and Information Engineering Penghu Taiwan

research on the study of houses, condominiums and buildings in Taiwan’s metropolitan areas continues to be an important area of research. In real estate forecasting and analysis, methods such as statistical analysis and questionnaire data collection are widely used. However, when multidimensional data is considered, these methods are time-consuming and inadequate. This study aimed to build a real estate forecasting model that can adapt to a changing environment. data were collected from public government databases, the collected data were standardized for accurate clustering, an appropriate data clustering algorithm was applied to the standardized data, and cross-statistical analysis was performed to verify the adopted algorithm. We used a deep learning based on autoencoder algorithm to increase the accuracy of the clustering analysis. A double-bottom map particle swarm optimization (dBM-PSO) clustering algorithm was then used to determine the optimal clustering solution. Cluster analysis and deep learning were conducted on data collected from public websites to understand the factors that led to the sustained increase in housing prices in Taiwan over the past decade. The results of this study indicate that three key factors—the number of real estate transactions, the average unit price of real estate transactions, and the building material and construction index—significantly affected real estate prices in Taiwan. Our results could help researchers and governments to focus on specific aspects of real estate development without being influenced by other related factors. In addition, the relationships between real estate trends and the aforementioned three key factors were determined to obtain valuable information that can enable the Taiwanese government to regulate the property market and prevent excessive growth. The framework proposed in this paper allows researchers and governments to focus on specific aspects of real estate development without being influenced b

关键词： Houses

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photothermal Temperature-Modulated Cancer Metastasis Harnessed Using Proteinase-Triggered Assembly of Near-Infrared II photoacoustic/photothermal Nanotheranostics

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ACS Applied Materials and Interfaces 2024年第31期16卷 40611-40627页

作者： Chuang, Yao-Chen Hsia, Yu Chu, Chia-Hui Maharajan, Sivasubramanian Hsu, Fang-Chi Lee, Hsin-Lun Chiou, Jeng Fong Ch’ang, Hui-Ju Liao, Lun-de Lo, Leu-Wei Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Miaoli Zhunan35053 Taiwan Department of Radiation Oncology Taipei Medical University Hospital Taipei110301 Taiwan Institute of Biotechnology National Tsing Hua University Hsinchu30013 Taiwan The Ph.D. Program for Translational Medicine College of Medical Science and Technology Taipei Medical University and Academia Sinica Taipei110301 Taiwan Department of Radiology School of Medicine College of Medicine Taipei Medical University Taipei110301 Taiwan National Institute of Cancer Research National Health Research Institutes Miaoli Zhunan35053 Taiwan

Here we demonstrate that cancer metastasis could be modulated by the judicious tuning of physical parameters such as photothermal temperature in nanoparticle-mediated photothermal therapy (PTT). This is supported by theranostic nanosystem design and characterization, in vitro and in vivo analyses, and transcriptome-based gene profiling. In this work, the highly efficient near-infrared II (NIR-II) photoacoustic image (PA)-guided PTT are selectively activated using our developed matrix metalloproteinase (MMP)-triggered in situ assembly of gold nanodandelions (GNds@gelatin). Unlike other "always-on" NIR PTT agents lacking specific bioactivation and suffering from the intrinsic nonspecific pseudosignals and treatment-related side effects such as metastasis, our GNds@gelatin possesses important advantages while deployed in cancer PTT that include the following: (1) The theranostic effects could be "turned on" only after specific MMP-2/-9 activity and with acidity in the tumor microenvironment. (2) The quantitative PA diagnosis allows for precise PTT planning for better cancer treatment. (3) GNds@gelatin could noninvasively quantify MMP activity and efficiently harness NIR-I (808 nm) and NIR-II (1064 nm) energies for tumor ablation. (4) The multibranched nanostructures reabsorb scattered laser photons, thus enhancing the surface plasmons for the pronounced photothermal conversion of aggregated GNds@gelatin in situ. (5) It is noteworthy that in situ tumor eradication at higher PTT temperature (>55 °C) mediated by GNds@gelatin could induce subsequent metastasis, which could be otherwise abolished at lower PTT temperatures (50 °C > T > 43 °C). (6) Furthermore, the gene profiling using transcriptome-based microarray including GO and KEGG analyses revealed that 315 differentially expressed genes were identified in higher PTT temperature treated tumors compared with lower PTT temperature ones. These were enriched into some well-known cancer-related pathways, such as cell migrat

关键词： Plasmonics

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TiO2 Hole Transport Layer Incorporated in a Thermally Evaporated Sb2Se3 photoelectrode Exhibiting Low Onset Potential for photoelectrochemical Applications

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Energy and Fuels 2024年第17期38卷 16936-16948页

作者： Xavier, Thatheyus Peter Piraviperumal, Malar Kuo, Chih-Yu Govindasamy, Mani Thinfilm Photovoltaics Laboratory Department of Physics and Nanotechnology SRM Institute of Science and Technology Tamil Nadu Kattankulathur603203 India Department of Chemical Engineering & Biotechnology National Taipei University of Technology Taipei City10608 Taiwan Research Center for Intelligence Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan Department of Research and Innovation Saveetha School of Engineering SIMATS Chennai602105 India Taipei10608 Taiwan International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan

developing cost-effective photoelectrodes with a low band gap in the NIR-visible regions remains a challenge to achieve effective hydrogen production. We report the details of superstrate-configured photocathodes, consisting of antimony selenide (Sb2Se3) light absorbing layers with titanium dioxide (TiO2) as a hole transport layer, exhibiting the capability for hydrogen evolution with broad range light absorption enabled by the low band gap value of ∼1.2 eV of Sb2Se3. Strong anisotropy is a significant characteristic property of Sb2Se3, allowing superior electrical transportation along the [hkl] crystallographic orientation, which is obtained via close space evaporation of presynthesized bulk material at a growth temperature of 250 °C, over the solution-processed TiO2 film on a fluorine-doped tin oxide (FTO) substrate. The superstrate-configured FTO/TiO2/Sb2Se3 photocathode exhibited a photocurrent density of 100 μA cm-2 at −0.3 V vs RHE in 0.5 M H2SO4 under 1 sun illumination. To further improve photocurrent density, Pt as a cocatalyst was deposited over Sb2Se3 that led to enhanced photocurrent to 3 mA cm-2 at −0.3 V vs RHE in 0.5 M H2SO4 under 1 sun illumination. despite the relatively lower photocurrent observed, which resulted due to a large conduction band offset (ΔECB = 0.99 eV) of the TiO2/Sb2Se3 interface in a superstrate configuration, a significantly lower onset potential of −0.1 V vs RHE was observed. The results are encouraging due to the low band gap of Sb2Se3, photocorrosion stability, and straightforward fabrication, which is expected to assist for significant outcomes. © 2024 American Chemical Society.

关键词： Titanium dioxide

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Synergistic sodium alginate- and biochar-immobilized cells for enhancing fermentative hydrogen production from food waste

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Environmental Science and Pollution research 2024年第56期31卷 64524-64533页

作者： Ngamnurak, phonsini Plangklang, Pensri Pomdaeng, Prakaidao Ko, Ting-Wu Reungsang, Alissara Chu, Chen-Yeon Graduate School Khon Kaen University Khon Kaen40002 Thailand Department of Biology Technology Faculty of Technology Khon Kaen University Khon Kaen40002 Thailand Research Group for Development of Microbial Hydrogen Production Process From Biomass Khon Kaen University Khon Kaen40002 Thailand Institute of Green Products Feng Chia University Taichung Taiwan Ph.D. Program of Mechanical and Aeronautical Engineering Feng Chia University Taichung Taiwan Master’s Program of Green Energy Science and Technology Feng Chia University Taichung Taiwan Academy of Science Royal Society of Thailand Bangkok10300 Thailand

An immobilized hydrogen-producing consortium investigated biohydrogen production from food waste using a combination of sodium alginate and cassava rhizome biochar. We investigated the effect of varying the biochar concentration from 0 to 3% and the size of immobilized cells from 1 to 7 mm. Immobilized cells were prepared using 50% (v/v) enriched hydrogen-producing consortium, 2% (w/v) sodium alginate, and 0 to 3% (w/v) cassava rhizome biochar. The optimal conditions for achieving the highest hydrogen production in the batch fermentation reactor were identified as a biochar concentration of 2% (w/v) and an immobilized cell size of 2 mm. The highest hydrogen yield, maximum hydrogen production rate, and lag time recorded were 0.69 mmol H2/g-COd, 0.02 mmol H2/g-COd.h, and 41.51 h, respectively. This research highlights the potential of cassava biochar technology for efficient biohydrogen production from food waste, contributing to renewable energy generation and sustainable waste management. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.

关键词： Anaerobic digestion

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New ent-kaurene and germacrene derivatives from Mesona procumbens Hemseley and their biological activity

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Natural Product research 2023年第13期37卷 2172-2180页

作者： Ganzon, Jerome G. Liaw, Chia-Ching Lin, Yu-Chi Lin, Zhi-Hu Wang, Chang-Hung Chen, Che-Yi Chuang, Kuo-Hsiang Kuo, Yao-Haur Division of Chinese Materia Medica Development National Research Institute of Chinese Medicine Taipei Taiwan Department of Biochemical Science and Technology National Chiayi University Chiayi Taiwan Ph.D. Program in Clinical Drug Development of Herbal Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Pharmacognosy College of Pharmacy Taipei Medical University Taipei Taiwan Graduate Institute of Integrated Medicine College of Chinese Medicine China Medical University Taichung Taiwan Department of Research and Development Starsci Biotech Co. Ltd Taoyuan Taiwan

Mesona procumbens Hemseley is a well-known traditional herbal medicine used for heat-related ailments. In Taiwan, boiled extracts of M. procumbens are also used as desserts called grass jelly. In this study, the hexane extract from 75% EtOH of M. procumbens showed potent activities on inhibition of E. coli β-glucuronidase (eβG) and NO production and cytotoxicity against MCF-7 and HepG2 cancer cell lines. Furthermore, using various flash columns and HPLC chromatography on the bioactive layer led to the isolation of twelve compounds (1–12), including a new ent-kaurene, mesokaurol A (1), and a new germacrene derivative, mesogermapene A (2). Their structures were elucidated by extensive spectroscopic analyses, especially 2 d NMR and mass data. Biological assays showed that compound 9 (linolenic acid) had specific activity on inhibition of eβG (68.27%) at 100 µg/mL but was non-inhibitory to human β-glucuronidase. Compound 1 possessed significant cytotoxicity against MCF-7 (EC₅₀ = 9.76 µM) and HepG2 (EC₅₀ = 8.64 µM) cancer cell lines. © 2022 Informa UK Limited, trading as Taylor & Francis Group.

关键词： Anti-β-glucuronidase cytotoxicity germacrene Kaurane-type diterpene Mesona procumbens Hemseley

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diphenyl disulfide potentiates the apoptosis of breast cancer cells through Bax proteolytic activation with accompanying autophagy

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Environmental Toxicology 2023年第8期38卷 2022-2030页

作者： Chen, Sheng-Yuan Chiu, Chien-Chih Hung, Chun-Tzu Pan, Wen-Hsiung Chen, Yen-Chun Bow, Yung-ding Li, Wan-Ju Hsu, Sheng-Kai Lin, I-Ling Wen, Zhi-Hong Wu, Chang-Yi Department of Medicine Division of Cardiology Zuoying Branch of Kaohsiung Armed Forces General Hospital Kaohsiung Taiwan Department of Biotechnology Kaohsiung Medical University Kaohsiung Taiwan Department of Biological Sciences National Sun Yat-Sen University Kaohsiung Taiwan Center for Cancer Research Kaohsiung Medical University Kaohsiung Taiwan National Laboratory Animal Center National Applied Research Laboratories Taipei Taiwan Department of Medical Research Kaohsiung Medical University Hospital Kaohsiung Taiwan Ph.D. Program in Life Sciences College of Life Science Kaohsiung Medical University Kaohsiung Taiwan Department of Medical Laboratory Science and Biotechnology Kaohsiung Medical University Kaohsiung Taiwan Department of Laboratory Medicine Kaohsiung Medical University Hospital Kaohsiung Taiwan Department of Marine Biotechnology and Research National Sun Yat-sen University Kaohsiung Taiwan

Breast cancer is a leading cause of cancer-related death worldwide, and chemoresistance often leads to poor patient outcomes. In this study, we investigated the anticancer activity of synthetic diphenyl disulfide (dPdS) in breast cancer cell lines. dPdS inhibited cellular proliferation and viability in a dose-dependent manner and reduced colony formation, an index of clonogenicity. Annexin-V and 7-AAd double staining showed that dPdS could induce the apoptosis of breast cancer cells. Western blotting of the expression of Bax p21 and its cleaved form p18 suggested the activation of p18 Bax-induced apoptosis. Furthermore, the increased expression of the autophagy marker LC3B-II indicated autophagic lysosome accumulation induced by dPdS. Our findings suggest that dPdS has potential as a candidate for treating breast cancer, and further modifications and optimizations are warranted. © 2023 Wiley Periodicals LLC.

关键词： Cell death

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Structure-Guided discovery of Pd-1/Pd-L1 Interaction Inhibitors: Peptide design, Screening, and Optimization via Computation-Aided phage display Engineering

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Journal of Chemical Information and Modeling 2024年第5期64卷 1615-1627页

作者： Tseng, Tien-Sheng Lee, Chao-Chang Chen, Po-Juei Lin, Chiu-Yuen Chen, Wang-Chuan Lee, Yu-Ching Lin, Jiun-Han Chen, Kaun-Wen Tsai, Keng-Chang Institute of Molecular Biology National Chung Hsing University Taichung40202 Taiwan National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei11221 Taiwan The School of Chinese Medicine for Post Baccalaureate I-Shou University Kaohsiung824005 Taiwan Department of Chinese Medicine E-Da Hospital Kaohsiung824005 Taiwan TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei11031 Taiwan Ph.D. Program in Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taipei11031 Taiwan Department of Industrial Technology Ministry of Economic Affairs Taipei100210 Taiwan Food Industry Research and Development Institute Hsinchu30062 Taiwan Molecular Science and Digital Innovation Center Genetics Generation Advancement Corporation Taipei11949 Taiwan

Cancer immunotherapy harnesses the immune system to combat tumors and has emerged as a major cancer treatment modality. The Pd-1/Pd-L1 immune checkpoint modulates interactions between tumor cells and T cells and has been extensively targeted in cancer immunotherapy. However, the monoclonal antibodies known to target this immune checkpoint have considerable side effects, and novel Pd-1/Pd-L1 inhibitors are therefore required. Herein, a peptide inhibitor to disrupt Pd-1/Pd-L1 interactions was designed through structure-driven phage display engineering coupled to computational modification and optimization. BetaPb, a novel peptide library constructed by using the known structure of Pd-1/Pd-L, was used to develop inhibitors against the immune checkpoint, and specific peptides with high affinity toward Pd-1 were screened through enzyme-linked immunosorbent assays, homogeneous time-resolved fluorescence, and biolayer interferometry. A potential inhibitor, B8, was preliminarily screened through biopanning. The binding affinity of B8 toward Pd-1 was confirmed through computation-aided optimization. Assessment of B8 variants (B8.1, B8.2, B8.3, B8.4, and B8.5) demonstrated their attenuation of Pd-1/Pd-L1 interactions. B8.4 exhibited the strongest attenuation efficiency at a half-maximal effective concentration of 0.1 μM and the strongest binding affinity to Pd-1 (equilibrium dissociation constant = 0.1 μM). B8.4 outperformed the known Pd-1/Pd-L1 interaction inhibitor PL120131 in disrupting Pd-1/Pd-L1 interactions, revealing that B8.4 has remarkable potential for modification to yield an antitumor agent. This study provides valuable information for the future development of peptide-based drugs, therapeutics, and immunotherapies for cancer. © 2024 American Chemical Society.

关键词： Peptides

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