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Modulation of gut microbiota by crude gac aril polysaccharides ameliorates diet-induced obesity and metabolic disorders

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International Journal of Biological Macromolecules 2024年第PT 2期273卷 133164页

作者： Lu, Tai-Jung Chiou, Wei-Chung Huang, Hsiu-Chen Pan, Heng-Chih Sun, Chiao-Yin Way, Tzong-der Huang, Cheng Department of Ph.D. Program for Biotechnology Industry China Medical University Taichung City406040 Taiwan Department of Biotechnology and Laboratory Science in Medicine National Yang Ming Chiao Tung University Taipei City112304 Taiwan Center for Teacher Education National Tsing Hua University Hsinchu City300044 Taiwan Department of Applied Science Nanda Campus National Tsing Hua University Hsinchu City300044 Taiwan Department of Nephrology Chang Gung Memorial Hospital Keelung City204201 Taiwan

Obesity is a global health challenge that causes metabolic dysregulation and increases the risk of various chronic diseases. The gut microbiome is crucial in modulating host energy metabolism, immunity, and inflammation and is influenced by dietary factors. Gac fruit (Momordica cochinchinensis), widely consumed in Southeast Asia, has been proven to have various biological activities. However, the composition and effect of crude gac aril polysaccharides (GAP) on obesity and gut microbiota disturbed by high-fat diet (HFd) remain to be elucidated. Compositional analysis showed that GAP contains high oligosaccharides, with an average of 7–8 saccharide units. To mimic clinical obesity, mice were first made obese by feeding HFd for eight weeks. GAP intervention was performed from week 9 to week 20 in HFd-fed mice. Our results showed that GAP inhibited body weight gain, eWAT adipocyte hypertroph., adipokine derangement, and hyperlipidemia in HFd-induced obese mice. GAP improved insulin sensitivity, impaired glucose tolerance, and hepatic steatosis. GAP modulated the gut microbiota composition and reversed the HFd-induced dysbiosis of at least 20 genera. Taken together, GAP improves metabolic health and modulates the gut microbiome to relieve obesity risk factors, demonstrating the potential of dietary GAP for treating obesity-associated disorders. © 2024 The Authors

关键词： Oligosaccharides

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2d sheet structure of zinc molybdate decorated on MXene for highly selective and sensitive electrochemical detection of the arsenic drug Roxarsone in water samples

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Chemosph.re 2024年 364卷 143188页

作者： Baskaran, Nareshkumar Prasanna, Sanjay Ballur Jeyaram, Kanimozhi Lin, Yu-Chien Govindasamy, Mani Wei, Yang Chung, Ren-Jei Taipei10608 Taiwan Department of Biotechnology Kalasalingam Academy of Research and Education Tamil Nadu Krishnankoil626126 India ZhongSun Co. LTD New Taipei City220031 Taiwan International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan Tamil Nadu Chennai602105 India Research Center for Intelligence Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan Taipei10608 Taiwan

Water contamination is a serious environmental issue posing a significant global challenge. Roxarsone (ROX), a widely used anticoccidial drug is excreted in urine and feces, potentially disrupting natural habitats. Therefore, rapid and cost-effective ROX detection is essential. In this study, we developed a 2d sheet structure of zinc molybdate decorated on MXene (ZnMoO4/MXene) for detecting ROX using electrochemical methods. The materials were characterized using appropriate spectroph.tometric and voltammetric techniques. The ZnMoO4/MXene hybrid exhibited excellent electrocatalytic performance due to its rapid electron transfer rate and higher electrical conductivity. The ZnMoO4/MXene-modified GCE (ZnMoO4/MXene/GCE) showed a broad linear range with high sensitivity (10.413 μA μМ−1 cm−2) and appreciable limit of detection (LOd) as low as 0.0081 μM. It also demonstrated significant anti-interference capabilities, excellent storage stability, and remarkable reproducibility. Furthermore, the feasibility of utilizing ZnMoO4/MXene/GCE for monitoring ROX in water samples was confirmed, achieving satisfactory recoveries. © 2024 Elsevier Ltd

关键词： Body fluids

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Clinical implications of hepatitis B virus core antigen-mediated immunopathologic T cell responses in chronic hepatitis B

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Journal of medical Virology 2024年第3期96卷 e29515-e29515页

作者： Wang, Li-Tzu Chen, Yu-Hong Cheng, Yang Fan, Hsiu-Lung Chen, Teng-Wei Shih, Yu-Lueng Hsieh, Tsai-Yuan Huang, Wen-Yen Huang, Wei-Chen School of Medical Laboratory Science and Biotechnology 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 Department of Internal Medicine Division of Gastroenterology Tri-Service General Hospital National Defense Medical Center Taipei Taiwan Division of Infectious Disease & Immunology Institute of Biomedical Science Academia Sinica Taipei Taiwan Department of Surgery Division of Organ Transplantation Surgery Tri-Service General Hospital National Defense Medical Center Taipei Taiwan Department of Radiation Oncology Tri-Service General Hospital National Defense Medical Center Taipei Taiwan

Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T-cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the ph.notypic features of HBV_core-specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV-specific T cells. In line with Taiwanese dominant HLA-alleles, we also evaluated ex vivo HBV_core-specific T cells by pMHC-tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed Cd8 T cells from CHB patients had higher activation marker Cd38 levels but showed an upregulation in the inhibitory receptor Pd-1. Our parallel study showed HBV-specific Cd8 T cells were more activated with greater Pd-1 expression than CMV-specific subset and bulk Cd8 T cells. Moreover, our longitudinal study demonstrated a correlation between the Pd-1 fluctuation pattern of HBV_core-specific Cd8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen-mediated immunopathologic profile of Cd8 T cells in chronic HBV infection. Our findings suggest the Pd-1 levels of HBV_core-specific Cd8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management. © 2024 The Authors. Journal of medical Virology published by Wiley Periodicals LLC.

关键词： HBcAg HBV hepatitis Pd-1 T cells

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dexamethasone and dexmedetomidine: A Synergistic Approach to Reduce Postoperative Nausea and Vomiting in Bariatric Surgery Patients

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Obesity surgery 2024年第6期34卷 2253-2254页

作者： Po-Chih Chang Ya-Wei Huang Chih-Kun Huang Ting-Wei Chang School of Medicine College of Medicine National Sun Yat-Sen University Kaohsiung City Taiwan. Division of Thoracic Surgery Department of Surgery Kaohsiung Medical University Hospital/Kaohsiung Medical University Kaohsiung City Taiwan. Weight Management Center Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung City Taiwan. Ph. D. Program in Biomedical Engineering College of Medicine Kaohsiung Medical University Kaohsiung City Taiwan. Department of Sports Medicine College of Medicine Kaohsiung Medical University Kaohsiung City Taiwan. Department of Nursing Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung City Taiwan. Body Science and Metabolic Disorders International Medical Center China Medical University Hospital Taichung City Taiwan. Division of Thoracic Surgery Department of Surgery Kaohsiung Medical University Hospital/Kaohsiung Medical University Kaohsiung City Taiwan. drchangtingwei@***. Weight Management Center Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung City Taiwan. drchangtingwei@***.

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#136 : Osteopontin Facilitates Embryo Growth, Implantation, and Cellular Metabolism via Interacting withαvβ3 and RGS2 Pathway: Evidence from Mouse Embryos and a 3d In-Vitro Implantation Model

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Fertility & Reproduction 2023年第4期5卷 706-706页

作者： Nguyen Tuong Ho Pei-Yu Liao Chii Tzeng Shu-Huei Kao International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei Taiwan School of Medical Laboratory Science and Biotechnology College of Medical Science and Technology Taipei Medical University Taipei Taiwan Taipei Fertility Center Taipei Taiwan Ph.D. Program in Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taipei Taiwan

Background and Aims: We conducted a study on mice to investigate how osteopontin, a mediator of cell-cell and cell-extracellular matrix (ECM) communication and invasion, influences embryonic development, metabolism, and implantation potential, with confirmation by a 3d in-vitro implantation model. Method: Embryos were collected from female mice and cultured under different conditions: HTF only, HTF supplemented with OPN at different doses, and OPN-supplemented HTF with anti- α v β 3 Ab or RGS2 inhibitors. Embryo morph.logy, development, and implantation rates were evaluated. Microarrays were used to evaluate gene expression profiling. Choriocarcinoma JAR and epithelial RL95-2 cell lines were adopted for the in-vitro implantation model. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were used to measure cellular metabolism levels. Results: The supplementation of OPN best enhanced the rate of embryo hatching-out and implantation onto the matrigel at 100 nM, but a higher degeneration rate was seen at a higher concentration ( ≥ 200 nM). In OPN-treated embryos, microarray analysis showed 51 significantly down-regulated genes and 60 up-regulated genes, including RGS2. Inhibition of α v β 3 integrin decreased embryo implantation rates and down-regulated RGS2. Validation of the 3d implantation model using JAR sph.roids and RL95-2 monolayer showed a similar effect. OPN also increased OCR and ECAR of the JAR cells, and migration assays revealed increased migration ability in OPN-overexpressed JAR cells, which was then inhibited by α v β 3 and RGS2 inhibitors. Conclusion: Osteopontin, at a reasonable concentration, could enhance embryo development and implantation by interacting with α v β 3 integrin, subsequently facilitating the RGS2 pathway. OPN has the potential to be a supplement during in vitro embryo culture in ART intervention.

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Chrysanthemum Flower-Like Nio-Coo Hybrid as Anode for High-Performance Lithium/Sodium-Ion Batteries: Understanding Capacitive and diffusive Li+/Na+ Charge Storage Kinetics

SSRN

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SSRN 2024年

作者： Kannadasan, Kalidoss Govindasamy, Mani Kuo, Chih-Yu Elumalai, Perumal Electrochemical Energy Storage Lab Department of Green Energy Technology Madanjeet School of Green Energy Technologies Pondicherry University Puducherry605014 India International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei24301 Taiwan Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei10608 Taiwan King Saud University Saudi Arabia

In this study, chrysanthemum flower-like nickel oxide – cobalt oxide (NiO-CoO) nano hybrid was generated hydrothermally and explored as an anode in lithium/sodium-ion batteries. Various characterization techniques were employed to analyze the crystal structure, chemical composition and morph.logy of the synthesized NiO-CoO nano hybrid. Electrochemical studies including cyclic voltammetry (CV), galvanostatic charge-discharge (GCd) and electrochemical impedance spectroscopy (EIS) were conducted to evaluate the lithium-ion and sodium-ion storage performances of the NiO-CoO nano hybrid electrode. It turned out that the lithium-ion battery half-cell constructed in the form of CR-2032 coin cell containing the NiO-CoO hybrid anode achieved a high specific capacity of 739 mA h g-1 at 0.1C-rate showed consistent 100% Coulombic efficiency over 100 charge-discharge cycles. Additionally, the sodium-ion battery performance was also investigated, delivering a specific capacity of 340 mA h g-1 at 0.1C-rate with stable cycle life over 100 cycles. Interestingly, a full-cell lithium-ion battery (NiO-CoO|1M LiPF6|LiCoO2) was assembled for the first time employing the NiO-CoO nano hybrid as anode. The fabricated CR-2032 coin-type LIB full-cell exhibited a specific capacity of 112 mA h g-1 at 0.1C-rate. Further the full cell LIB was demonstrated for practical applications such as powering commercial LEd bulbs and a temperature sensor. The fabricated full-cell sustained illumination of a green LEd bulb for over 5 hours on a single charge. The fascinating flower-like morph.logy of the NiO-CoO hybrid led to better interaction with the electrolyte and offered short diffusion path as well as efficient conversion/re-conversion reactions which in turn led to high charge storage. © 2024, The Authors. All rights reserved.

关键词： Anodes

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Functional Peptide-Loaded Gelatin Nanoparticles as Eyedrops for Cornea Neovascularization Treatment

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International Journal of Nanomedicine 2023年 18卷 1413-1431页

作者： Chu, Ya-Chun Fang, Hsu-Wei Wu, Yu-Yi Tang, Yu-Jun Hsieh, Erh-Hsuan She, Yizhou Chang, Che-Yi Lin, I-Chan Chen, Yin-Ju Liu, Guei-Sheung Tseng, Ching-Li Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei City Taiwan Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei City Taiwan Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Miaoli County Taiwan School of Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei City Taiwan Department of Ophthalmology Wan Fang Hospital Taipei Medical University Taipei City Taiwan Department of Ophthalmology School of Medicine College of Medicine Taipei Medical University Taipei City Taiwan Department of Radiation Oncology Taipei Medical University Hospital Taipei City Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei City Taiwan Center for Precision Medicine and Translational Cancer Research Taipei Medical University Hospital Taipei City Taiwan Centre for Eye Research Australia Royal Victorian Eye and Ear Hospital East Melbourne VIC Australia Ophthalmology Department of Surgery University of Melbourne East Melbourne VIC Australia Menzies Institute for Medical Research University of Tasmania Hobart TAS Australia Research Center of Biomedical Device College of Biomedical Engineering Taipei Medical University Taipei City Taiwan

Background: Corneal neovascularization (NV) is a process of abnormal vessel growth into the transparent cornea from the limbus and can disturb the light passing through the cornea, resulting in vision loss or even blindness. The use of nanomedicine as an effective therapeutic formulation in oph.halmology has led to higher drug bioavailability and a slow drug release rate. In this research, we designed and explored the feasibility of a new nanomedicine, gp91 ds-tat (gp91) peptide-encapsulated gelatin nanoparticles (GNP-gp91), for inhibiting corneal angiogenesis. Methods: GNP-gp91 were prepared by a two-step desolvation method. The characterization and cytocompatibility of GNP-gp91 were analyzed. The inhibition effect of GNP-gp91 on HUVEC cell migration and tube formation was observed by an inverted microscope. The drug retention test in mouse cornea was observed by in vivo imaging system, fluorescence microscope, and dAPI/TAMRA staining. Finally, the therapeutic efficacy and evaluation of neovascularization-related factors were conducted through the in vivo corneal NV mice model via topical delivery. Results: The prepared GNP-gp91 had a nano-scale diameter (550.6 nm) with positive charge (21.7 mV) slow-release behavior (25%, 240hr). In vitro test revealed that GNP-gp91 enhanced the inhibition of cell migration and tube formation capacity via higher internalization of HUVEC. Topical administration (eyedrops) of the GNP-gp91 significantly prolongs the retention time (46%, 20 min) in the mouse cornea. In chemically burned corneal neovascularization models, corneal vessel area with a significant reduction in GNP-gp91 group (7.89%) was revealed when compared with PBS (33.99%) and gp91 (19.67%) treated groups via every two days dosing. Moreover, GNP-gp91 significantly reduced the concentration of Nox2, VEGF and MMP9 in NV’s cornea. Conclusion: The nanomedicine, GNP-gp91, was successfully synthesized for oph.halmological application. These data suggest that GNP-gp91 contain

关键词： control release corneal neovascularization eye drops gelatin gp91 peptide nanoparticles ocular retention

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Inhibition of dengue viruses by N-methylcytisine thio derivatives through targeting viral envelope protein and NS2B-NS3 protease

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Bioorganic and Medicinal Chemistry Letters 2024年 99卷 129623页

作者： Lin, Chen-Sheng Lu, Chih-Hao Lin, Tsai-Hsiu Kiu, Yan-Tung Kan, Ju-Ying Chang, Yu-Jen Hung, Ping-Yi Tsypyshev, dmitry O. Tsypysheva, Inna P. Lin, Cheng-Wen Division of Gastroenterology Kuang Tien General Hospital No. 117 Shatian Rd Shalu District Taichung City 433 Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu City Taiwan Department of Medical Laboratory Science and Biotechnology China Medical University Taichung 40402 Taiwan Department of Laboratory Medicine China Medical University Hospital Taichung 40402 Taiwan The Ph.D. Program of Biotechnology and Biomedical Industry China Medical University Taichung Taiwan Ufa Institute of Chemistry Ufa Federal Research Centre of the Russian Academy of Sciences 71 prosp. Oktyabrya Ufa 450054 Russian Federation Department of Medical Laboratory Science and Biotechnology Asia University Taichung41354 Taiwan

dengue virus (dENV) is a significant global health threat, causing millions of cases worldwide each year. developing antiviral drugs for dENV has been a challenging endeavor. Our previous study identified anti-dENV properties of two (-)-cytisine derivatives contained substitutions within the 2-pyridone core from a pool of 19 (-)-cytisine derivatives. This study aimed to expand on the previous research by investigating the antiviral potential of N-methylcytisine thio (mCy thio) derivatives against dENV, understanding the molecular mechanisms of antiviral activity for the active thio derivatives. The inhibitory assays on dENV-2-induced cytopathic effect and infectivity revealed that mCy thio derivatives 3 ((1R,5S)-3-methyl-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocine-8-thione) and 6 ((1S,5R)-3-methyl-2-thioxo-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one) were identified as the active compounds against both dENV-1 and dENV-2. derivative 6 displayed robust antiviral activity against dENV-2, with EC₅₀ values ranging from 0.002 to 0.005 μM in different cell lines. derivative 3 also exhibited significant antiviral activity against dENV-2. The study found that these compounds are effective at inhibiting dENV-2 at both the entry stage (including virus attachment) and post-entry stages of the viral life cycle. The study also investigated the inhibition of the dENV-2 NS2B-NS3 protease activity by these compounds. derivative 6 demonstrated notably stronger inhibition compared to mCy thio 3, revealing its dual antiviral action at both the entry and post-entry stages. Molecular docking simulations indicated that mCy thio derivatives 3 and 6 bind to the domain I and III of the dENV E protein, as well as the active of NS2B-NS3 protease, suggesting their molecular interactions with the virus. The study demonstrates the antiviral efficacy of N-methylcytisine thio derivatives against dENV. It provides valuable insights into the pot

关键词： Antiviral Attachment dengue virus E protein Entry N-methylcytisine thio derivative NS2B-NS3 protease Post-entry

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Targeting human mitochondrial NAd(P)+-dependent malic enzyme (ME2) impairs energy metabolism and redox state and exhibits antileukemic activity in acute myeloid leukemia

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Cellular Oncology 2023年第5期46卷 1301-1316页

作者： Chen, Kun-Chi Hsiao, I-Hsin Huang, Yu-Nan Chou, Yu-Tung Lin, Yi-Chun Hsieh, Ju-Yi Chang, Yung-Lung Wu, Kang-Hsi Liu, Guang-Yaw Hung, Hui-Chih Department of Life Sciences National Chung Hsing University Taichung Taiwan Ph.D. Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung Taiwan Department of Biochemistry National Defense Medical Center Taipei Taiwan School of Medicine Chung Shan Medical University Taichung Taiwan Department Pediatrics Chung Shan Medical University Hospital Taichung Taiwan Institute of Medicine College of Medicine Chung Shan Medical University Taichung Taiwan Institute of Genomics and Bioinformatics National Chung Hsing University Taichung Taiwan EGG & Animal Biotechnology Center National Chung Hsing University Taichung Taiwan

Acute myeloid leukemia (AML) is a fast-growing and highly fatal blood cancer, and recent research has shown that targeting metabolism may be a promising therapeutic approach for treating AML. One promising target is the human mitochondrial NAd(P)+-dependent malic enzyme (ME2), which is involved in the production of pyruvate and NAd(P)H and the regulation of the NAd+/NAdH redox balance. Inhibition of ME2 via silencing ME2 or utilizing its allosteric inhibitor disodium embonate (Na2EA) causes a decrease in pyruvate and NAdH, leading to a decrease in producing ATP via cellular respiration and oxidative ph.sph.rylation. ME2 inhibition also decreases NAdph.levels, resulting in an increase in reactive oxygen species (ROS) and oxidative stress, which ultimately leads to cellular apoptosis. Additionally, ME2 inhibition reduces pyruvate metabolism and the biosynthetic pathway. ME2 silencing inhibits the growth of xenotransplanted human AML cells, and the allosteric ME2 inhibitor Na2EA demonstrates antileukemic activity against immune-deficient mice with disseminated AML. Both of these effects are a result of impaired energy metabolism in mitochondria. These findings suggest that the targeting ME2 may be an effective strategy for treating AML. Overall, ME2 plays an essential role in energy metabolism of AML cells, and its inhibition may offer a promising approach for AML treatment.

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Flexibanone, the first cembranoid possessing an α-methylene-δ-lactone linking with a tetrahydronfuran ring by C-3/C-4 single bond, from the soft coral Sinularia flexibilis

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Tetrahedron Letters 2023年 129卷

作者： Tai, Chi-Jen Zhang, Hong-Wei Wang, Hui-Chun Chuang, Ya-Ting Chang, Hsueh-Wei Chang, Fang-Rong Sung, Ping-Jyun Sheu, Jyh-Horng Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung 804201 Taiwan National Museum of Marine Biology and Aquarium Pingtung 944401 Taiwan Graduate Institute of Natural Products Kaohsiung Medical University Kaohsiung 807378 Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung 807378 Taiwan Ph.D. Program in Pharmaceutical Biotechnology Fu Jen Catholic University New Taipei City 242062 Taiwan Department of Medical Research China Medical University Hospital China Medical University Taichung 404394 Taiwan

A new cembranoid, flexibanone (1), and a known related diterpene sinulariolone (2) were isolated from a Taiwanese soft coral Sinularia flexibilis. Compound 1 is the first cembranoid possessing an α-methylene-δ-lactone linking with a tetrahydronfuran ring by C-3/C-4 single bond. The structures of 1 and 2 were established by using extensive spectroscopic analysis, including 2d NMR methods. Both compounds were suggested to be biosynthesized from the same cembranoid precursor. Further, the cytotoxicity against human oral cancer Ca9-22, breast adenocarcinoma MdA-MB-231 and non-small cell lung cancer A549 cell lines of 1 and 2 were also assayed. © 2023 Elsevier Ltd

关键词： Cembranoid-related compounds Cytotoxicity Flexibanone Sinularia flexibilis

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