检索结果-内蒙古大学图书馆

Wernicke Enceph.lopathy After Roux-en-Y Gastric Bypass Presenting with Altered Mental Status—A Video Case Report

Obesity Surgery 2024年第6期34卷 2271-2273页

作者： Chen, Chih-Chiang Chang, Po-Chih Chang, Ting-Wei Chuang, Hui-Yu Department of Surgery Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung City Taiwan 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 Department of Sports Medicine College of Medicine Kaohsiung Medical University Kaohsiung City Taiwan Ph. D. Program in Biomedical Engineering College of Medicine Kaohsiung Medical University Kaohsiung City Taiwan Department of Obstetrics and Gynecology Kaohsiung Medical University Hospital Kaohsiung Medical University No. 100 Tzyou 1st Road Kaohsiung City 80756 Taiwan

Wernicke enceph.lopathy (WE) is a seldom encountered yet significant neuropsychiatric ailment resulting from a deficiency in thiamine (vitamin B1). While commonly linked with chronic alcoholism or insufficient dietary intake, instances of WE following bariatric and metabolic surgeries, notably laparoscopic Roux-en-Y gastric bypass (RYGB), have been sporadically documented. This case study elucidates the condition of a male patient who, 3 months after undergoing RYGB to address severe obesity, displayed abrupt alterations in mental status, swiftly ameliorated by immediate administration of intravenous high-dose thiamine. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.

关键词： Laparoscopic Roux-en-Y gastric bypass Severe obesity Wernicke enceph.lopathy

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Enhancing wound healing and adhesion through dopamine-assisted gelatin-silica hybrid dressings

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International Journal of Biological Macromolecules 2024年第Part2期258卷 128845页

作者： Lin, Yu-Chien Wang, Huey-Yuan Tang, Yao-Chun Lin, Wan-Rong Tseng, Ching-Li Hu, Chih-Chien Chung, Ren-Jei Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei10608 Taiwan School of Materials Science and Engineering Nanyang Technological University 50 Nanyang Avenue Singapore639798 Singapore Department of Stomatology MacKay Memorial Hospital Taipei104217 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan International Ph. D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Research Center of Biomedical Device College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan International Ph. D. Program in Cell Therapy and Regenerative Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Bone and Joint Research Center Chang Gung Memorial Hospital Linkou33305 Taiwan Taipei10608 Taiwan

Gelatin, widely employed in hydrogel dressings, faces limitations when used in high fluid environments, hindering effective material adhesion to wound sites and subsequently reducing treatment efficacy. The rapid degradation of conventional hydrogels often results in breakdown before complete wound healing. Thus, there is a pressing need for the development of durable adhesive wound dressings. In this study, 3-glycidoxypropyltrimethoxysilane (GPTMS) was utilized as a coupling agent to create gelatin-silica hybrid (G-H) dressings through the sol-gel method. The coupling reaction established covalent bonds between gelatin and silica networks, enhancing structural stability. dopamine (dP) was introduced to this hybrid (G-H-d) dressing to further boost adhesiveness. The efficacy of the dressings for wound management was assessed through in-vitro and in-vivo tests, along with ex-vivo bioadhesion testing on pig skin. Tensile bioadhesion tests demonstrated that the G-H-d material exhibited approximately 2.5 times greater adhesion to soft tissue in wet conditions compared to pure gelatin. Moreover, in-vitro and in-vivo wound healing experiments revealed a significant increase in wound healing rates. Consequently, this material shows promise as a viable option for use as a moist wound dressing. © 2023

关键词： Adhesion

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Structure-Guided discovery of Pd-1/Pd-L1 Interaction Inhibitors: Peptide design, Screening, and Optimization via Computation-Aided ph.ge 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 ph.ge 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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Low-concentration imiquimod treatment promotes enhanced skin barrier functions through epidermal melanization reaction regulation

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Environmental Toxicology 2024年第9期39卷 4360-4371页

作者： Lin, Tzu-Kai Tsai, Chia-Lun Tsai, Bruce Chi-Kang Kuo, Chia-Hua Ho, Tsung-Jung Hsieh, dennis Jine-Yuan Kuo, Wei-Wen Huang, Chih-Yang Department of Dermatology Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan School of Medicine Tzu Chi University Hualien Taiwan Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Institute of Sports Sciences University of Taipei Taipei Taiwan Laboratory of Exercise Biochemistry Institute of Sports Sciences University of Taipei Tianmu Campus Taipei Taiwan Department of Kinesiology and Health Science College of William and Mary WilliamsburgVA United States Department of Chinese Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Integration Center of Traditional Chinese and Modern Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan School of Post-Baccalaureate Chinese Medicine College of Medicine Tzu Chi University Hualien Taiwan School of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung Taiwan Clinical Laboratory Chung Shan Medical University Hospital Taichung Taiwan Department of Biological Science and Technology College of Life Sciences China Medical University Taichung Taiwan Ph.D. Program for Biotechnology Industry China Medical University Taichung Taiwan School of Pharmacy China Medical University Taichung Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Department of Medical Research China Medical University Hospital China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan Center of General Education Buddhist Tzu Chi Medical Foundation Tzu Chi University of Science and Technology Hualien Taiwan

The primary function of the skin is to form a mechanical, permeability, antimicrobial, and ultraviolet radiation barrier, which is essential for maintaining ph.siological homeostasis. Our previous studies demonstrated that cutaneous pigmentation could promote skin barrier function in addition to providing anti-ultraviolet irradiation defense. The present study aimed to develop a new regimen that enhances skin barrier function by regulating skin pigmentation using low-concentration imiquimod. Results showed that topical application of low-concentration imiquimod effectively induced skin hyperpigmentation in the dorsal skin and external ear of mice without inducing inflammatory cell infiltration. An in vitro study also revealed that low-concentration imiquimod did not induce any cytotoxic effects on melanoma cells but triggered excessive melanin synthesis. In coculture systems, low-concentration imiquimod was noted to increase tyrosinase activity in a broader cellular context, revealing the potential role of neighboring cells in melanin production. The next-generation sequencing result indicated that PKCη and dnm3 might regulate melanin synthesis and release during imiquimod treatment. Overall, our study presents new insights into the regulation of melanin production by low-concentration imiquimod, both in a mice model and cultured cells. Furthermore, our study highlights the potential benefits of imiquimod in promoting melanin synthesis without causing skin disruptions or inducing inflammation, validating its potential to serve as a method for enhancing skin barrier functions by regulating the epidermal melanization reaction. © 2024 Wiley Periodicals LLC.

关键词： Irradiation

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Ex vitro rooting of minicutting of Carica papaya L. single shoot from tissue culture

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In Vitro Cellular and developmental Biology - Plant 2023年第3期59卷 393-400页

作者： Chen, Yu-Ting Yang, Tun-Han Yu, Tsong-Ann Ph.D. Program in Medical Biotechnology National Chung Hsing University 145 Xingda Rd. South Dist Taichung City 402 Taiwan Institute of Genomics and Bioinformatics National Chung Hsing University 145 Xingda Rd. South Dist Taichung City 402 Taiwan Department of Biomedical Sciences Da-Yeh University 168 University Rd Changhua County Dacun Township 515 Taiwan

Papaya (Carica papaya L.) is an important economic crop. An efficient and low-cost propagation ex vitro process is required for commercial papaya plantlet production. In this study, a propagation process of papaya was established by minicutting and evaluating parameters affecting survival. Individual shoots (1.5 cm) were cut from papaya multiple shoots in vitro as the minicuttings. After dipping in 400.0 mg L⁻¹ indole-3-butyric acid (IBA), they were planted into the nursery pro trays with 104 holes containing vermiculite, perlite, and King Root® substrate at 1:1:1 ratio, and then covered with a lid to keep the ratio of humidity (RH) at 100% for root development. After a 3-wk treatment in a growth chamber (28°C), the rooting rate, root number, root length, and stem length were promoted to 91.1%, 2.9, 3.71 cm, and 1.88 cm, respectively. Combining the treatment with 400 mg L⁻¹ IBA and 1/2 Murashige and Skoog (MS) salt solution supplemented at the 14th day after cutting gives the best growth potential for papaya plantlets, especially increasing root length to 4.55 cm. It also effectively enhances the survival rate of plantlets to 93.3%. This process saves the rooting initiation medium and time cost and avoids the complicated procedure of cleaning medium from root surface, which results in root damage. Under this minicutting process, the papaya plantlets thrived and were optimally suited to field cultivation. © 2023, The Society for In Vitro Biology.

关键词： Ex vitro Minicutting Papaya rooting Survival rate

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Rhodiola and Salidroside Attenuate Oxidative Stress-Triggered H9c2 Cardiomyoblast Apoptosis Through IGF1R-Induced ERK1/2 Activation

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Environmental Toxicology 2024年第11期39卷 5150-5161页

作者： Ju, I-Ju Tsai, Bruce Chi-Kang Kuo, Wei-Wen Kuo, Chia-Hua Lin, Yueh-Min Hsieh, dennis Jine-Yuan Pai, Pei-Ying Huang, Shang-En Lu, Shang-Yeh Lee, Shin-da Huang, Chih-Yang Division of General Medicine Department of Medical Education Tri-Service General Hospital National Defense Medical Center Taipei Taiwan Department of Neurological Surgery Tri-Service General Hospital National Defense Medical Center Taipei Taiwan Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Department of Biological Science and Technology College of Life Sciences China Medical University Taichung Taiwan Ph.D. Program for Biotechnology Industry China Medical University Taichung Taiwan School of Pharmacy China Medical University Taichung Taiwan Laboratory of Exercise Biochemistry University of Taipei Taipei Taiwan Institute of Sports Sciences University of Taipei Taipei Taiwan Department of Kinesiology and Health Science College of William and Mary WilliamsburgVA United States School of Physical Education and Sports Science Soochow University Jiangsu Suzhou China Department of Pathology Changhua Christian Hospital Changhua Taiwan School of Medicine Chung Shan Medical University Taichung Taiwan School of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung Taiwan Clinical Laboratory Chung Shan Medical University Hospital Taichung Taiwan Division of Cardiovascular Medicine Department of Internal Medicine China Medical University Hospital Taichung Taiwan School of Medicine College of Medicine China Medical University Taichung Taiwan Graduate Institute of Chinese Medicine China Medical University Taichung Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan School of Rehabilitation Science Shanghai University of Traditional Chinese Medicine Shanghai China School of Rehabilitation Medicine Weifang Medical University Shandong Weifang China Department of Physical Therapy Graduate Institute of Rehabilitation Science China Medical University Taichung Taiwan Department of Medical Research China Medic

Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. Rhodiola, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a ph.nylpropanoid glycoside derived from Rhodiola rosea, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of Rhodiola and salidroside against H2O2-induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H2O2 for 4 h, and subsequently treated with Rhodiola or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin-like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H2O2 (100 μM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with Rhodiola (12.5, 25, and 50 μg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H2O2-induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R-activated ph.sph.rylation of ERK1/2, leading to the inhibition of Fas-dependent proteins, HIF-1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of Rhodiola and salidroside in H9c2 cells against oxidative damage. Our findings suggest that Rhodiola and salidroside possess antioxidative properties that mitigate H2O2-induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent ph.sph.rylation of ERK1/2. These results propose Rhodiola and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health. © 2024 Wiley Periodicals LLC.

关键词： Cell death

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Prediction tools for assessing functional impacts of gene mutations in Clear Cell Renal Cell Carcinoma: A comparative study

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Computers in Biology and Medicine 2025年第Pt A期192卷 110187-110187页

作者： Yang, Cheng-Hong Lin, Guan-Cheng Wu, Chih-Hsien Chen, Jin-Bor 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 Drug Development and Value Creation Research Center Kaohsiung Taiwan Ph. D. Program in Biomedical Engineering Kaohsiung Medical University Kaohsiung Taiwan Division of Nephrology Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Taiwan Department of Chemical Engineering & Institute of Biotechnology and Chemical Engineering I-Shou University Kaohsiung Taiwan Taiwan

Renal cell carcinoma (RCC) is a well-known malignancy characterized by specific gene mutations that elevate its occurrence. It can be categorized into clear cell RCC (ccRCC), papillary RCC, and chromoph.be RCC, which account for approximately 85 % of all primary RCC cases. The mutations typically involve single-nucleotide variants (SNVs) that lead to amino acid substitutions, which influence various biological functions, including gene expression. Therefore, predicting the functional consequences of RCC-related single-nucleotide polymorph.sms (SNPs), including substitutions, insertions, deletions, and duplications, is crucial for the effective clinical management of RCC. In recent years, the accessibility and popularity of tools for predicting SNP functional variations have grown, especially in research concerning the potential risks associated with key gene mutations in cancer. Accordingly, this study focused on commonly mutated genes in ccRCC, namely VHL, BAP1, PBRM1, and SETd2. Public data from sources such as The Cancer Genome Atlas and the National Center for biotechnology Information were used to identify 61 gene mutation positions. Nine nonsynonymous mutation prediction tools were used for analysis, namely SIFT, Polyph.n-2, Mutation Assessor, Fathmm, MutPred, CHASM, Revel, Provean, and SNP&GO. The tools were evaluated by their statistical performance, prediction distribution, and receiver operating characteristic curves. The three tools with the highest accuracy for predicting the functional consequences of mutations in the four frequently mutated genes associated with ccRCC were SIFT (accuracy of 0.75), Provean (0.7), and Polyph.n-2 (0.69). These findings offer valuable insights into predicting ccRCC-related gene mutation effects, but further research and validation are essential to support their clinical applications. © 2025

关键词： Transcription

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Ser38-His93-Asn91 triad confers resistance of JFH1 HCV NS5A-Y93H variant to NS5A inhibitors

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FEBS Journal 2024年第6期291卷 1264-1274页

作者： Lee, Wei-Ping Tsai, Keng-Chang Liao, Shi-Xian Huang, Yi-Hsiang Hou, Ming-Chih Lan, Keng-Hsin Department of Medical Research Taipei Veterans General Hospital Taiwan Institute of Biochemistry and Molecular Biology School of Life Sciences National Yang Ming Chiao Tung University Taipei Taiwan National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei Taiwan The Ph.D. Program for Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taiwan Division of Gastroenterology and Hepatology Department of Medicine Taipei Veterans General Hospital Taiwan School of Medicine College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Institute of Clinical Medicine School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Institute of Pharmacology College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan

HCV NS5A is a dimeric ph.sph.protein involved in HCV replication. NS5A inhibitors are among direct-acting antivirals (dAA) for HCV therapy. The Y93H mutant of NS5A is resistant to NS5A inhibitors, but the precise mechanism remains unclear. In this report, we proposed a Ser38-His93-Asn91 triad to dissect the mechanism. Using pymol 1.3 software, the homology structure of JFH1 NS5A was determined based on the dimer structure of genotype 1b extracted from the database Protein dataBank (***/pdbsum) with codes 1ZH1 and 3FQM/3FQQ. FLAG-NS5A-WT failed to form dimer in the absence of nonstructural proteins from subgenomic replicon (NS3-5A);however, FLAG-NS5A-Y93H was able to form dimer without the aid of NS3-5A. The Ser38-His93-Asn91 triad in the dimer of the Y93H variant predicts a structural crash of the cleft receiving the NS5A inhibitor daclatasvir. The dimerization assay revealed that the existence of JFH1-NS5A-1ZH1 and -3FQM homology dimers depended on each other for existence and that both NS5A-WT 1ZH1 and 3FQM dimers cooperated to facilitate RNA replication. However, NS5A-Y93H 1ZH1 alone could form dimer and conduct RNA replication in the absence of the 3FQM structure. In conclusion, this study provides novel insight into the functional significance of the Ser38-His93-Asn91 triad in resistance of the Y93H variant to NS5A inhibitors. © 2023 Federation of European Biochemical Societies.

关键词： dimerization drug resistance Hepatitis C virus inhibitor NS5A Y93H mutant

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Injectable cross-linked hyaluronic acid hydrogels with epigallocatechin gallate loading as vitreous substitutes

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International Journal of Biological Macromolecules 2024年第Part1期275卷 133467页

作者： Chen, Huai-An Tai, Yi-Ning Hsieh, Erh-Hsuan Thacker, Minal Lin, I-Chan Tseng, Ching-Li Lin, Feng-Huei Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Shuang-Ho Campus New Taipei City Taiwan Institute of Biomedical Engineering College of Medicine & College of Engineering National Taiwan University Taipei City Taiwan 17W Hong Kong Science Park Hong Kong 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 International Ph. D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Shuang-Ho Campus New Taipei City Taiwan Research Center of Biomedical Device College of Biomedical Engineering Taipei Medical University Taipei City Taiwan International Ph. D. Program in Cell Therapy and Regenerative Medicine College of Medicine Taipei Medical University Taipei City Taiwan National Health Research Institutes Miaoli County Taiwan

Hyaluronic acid (HA) serves as a vitreous substitute owing to its ability to mimic the ph.sical functions of native vitreous humor. However, pure HA hydrogels alone do not provide sufficient protection against potential inflammatory risks following vitrectomy. In this study, HA was crosslinked with 1,4-butanediol diglycidyl ether (BddE) to form HA hydrogels (HB). Subsequently, the anti-inflammatory agent epigallocatechin gallate (EGCG) was added to the hydrogel (HBE) for oph.halmic applications as a vitreous substitute. The characterization results indicated the successful preparation of HB with transparency, refractive index, and osmolality similar to those of native vitreous humor, and with good injectability. The anti-inflammatory ability of HBE was also confirmed by the reduced expression of inflammatory genes in retinal pigment epithelial cells treated with HBE compared with those treated with HB. In a New Zealand white rabbit model undergoing vitreous substitution treatment, HBE 50 (EGCG 50 μM addition) exhibited positive results at 28 days post-surgery. These outcomes included restored intraocular pressure, improved electroretinogram responses, minimal increase in corneal thickness, and no inflammation during histological examination. This study demonstrated the potential of an injectable HA-BddE cross-linked hydrogel containing EGCG as a vitreous substitute for vitrectomy applications, offering prolonged degradation time and anti-inflammatory effects postoperatively. © 2024 The Authors

关键词： Hyaluronic acid

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Improving iPSC differentiation Using a Nanodot Platform

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ACS Applied Materials and Interfaces 2024年第28期16卷 36030-36046页

作者： Chiew, Men Yee Wang, Erick Lan, Kuan-Chun Lin, Yan-Ren Hsueh, Yu-Huan Tu, Yuan-Kun Liu, Chu-Feng Chen, Po-Chun Lu, Huai-En Chen, Wen Liang Center for Regenerative Medicine and Cellular Therapy National Yang Ming Chiao Tung University Hsinchu300 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu300 Taiwan College of Biological Science and Technology Industrial Ph. D. Program National Yang Ming Chiao Tung University Hsinchu300 Taiwan Kyoto University Kyoto606-8397 Japan Department of Emergency and Critical Care Medicine Changhua Christian Hospital Changhua500 Taiwan Department of Post Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung402 Taiwan School of Medicine Kaohsiung Medical University Kaohsiung807 Taiwan School of Medicine Chung Shan Medical University Taichung402 Taiwan College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu300 Taiwan Department of Orthopedic Surgery E-Da Hospital I-Shou University Kaohsiung824 Taiwan Emergency Medicine Department Kaohsiung Chang Gung Memorial Hospital Kaohsiung833 Taiwan Ph. D. Degree Program of Biomedical Science and Engineering National Yang Ming Chiao Tung University Hsinchu300 Taiwan Institute of Materials Science and Engineering National Taipei University of Technology Taipei106 Taiwan Institute of Biochemistry and Molecular Biology National Yang Ming Chiao Tung University Hsinchu300 Taiwan Bioresource Collection and Research Center Food Industry Research and Development Institute Hsinchu City300 Taiwan

differentiation of induced pluripotent stem cells (iPSCs) is an extremely complex process that has proven difficult to study. In this research, we utilized nanotopograph. to elucidate details regarding iPSC differentiation by developing a nanodot platform consisting of nanodot arrays of increasing diameter. Subjecting iPSCs cultured on the nanodot platform to a cardiomyocyte (CM) differentiation protocol revealed several significant gene expression profiles that were associated with poor differentiation. The observed expression trends were used to select existing small-molecule drugs capable of modulating differentiation efficiency. BRd K98 was repurposed to inhibit CM differentiation, while iPSCs treated with NSC-663284, carmofur, and KPT-330 all exhibited significant increases in not only CM marker expression but also spontaneous beating, suggesting improved CM differentiation. In addition, quantitative polymerase chain reaction was performed to determine the gene regulation responsible for modulating differentiation efficiency. Multiple genes involved in extracellular matrix remodeling were correlated with a CM differentiation efficiency, while genes involved in the cell cycle exhibited contrasting expression trends that warrant further studies. The results suggest that expression profiles determined via short time-series expression miner analysis of nanodot-cultured iPSC differentiation can not only reveal drugs capable of enhancing differentiation efficiency but also highlight crucial sets of genes related to processes such as extracellular matrix remodeling and the cell cycle that can be targeted for further investigation. Our findings confirm that the nanodot platform can be used to reveal complex mechanisms behind iPSC differentiation and could be an indispensable tool for optimizing iPSC technology for clinical applications. © 2024 The Authors. Published by American Chemical Society.

关键词： Efficiency

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