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PCGF6 regulates stem cell pluripotency as a transcription activator via super-enhancer dependent chromatin interactions

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Protein & Cell 2019年第10期10卷 709-725页

作者： Xiaona Huang Chao Wei Fenjie Li Lumeng Jia Pengguihang Zeng Jiahe Li Jin Tan Tuanfeng Sun Shaoshuai Jiang Jia Wang Xiuxiao Tang Bin Liu Limin Rong Cheng Li Junjun Ding RNA Biomedical Institute Sun Yat-Sen Memorial HospitalZhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China Center for Stem Cell Biology and Tissue Engineering Key Laboratory for Stem Cells and Tissue EngineeringMinistry of EducationSun Yat-Sen UniversityGuangzhou 510080China Department of Cell Biology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Program in Stem Cell and Regenerative Medicine The Third Affiliated Hospital of Sun Yat-sen UniversityZhongshan School of MedicineSun Yat-Sen UniversityGuangzhouChina Center for Bioinformatics School of Life SciencesPeking UniversityBeijing 100871China Department of Spine Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Histology and Embryology School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhou 511436China

Polycomb group(PcG)ring finger protein 6(PCGF6),though known as a member of the transcription-re-pressing complexes,PcG,also has activation function in regulating pluripotency gene ***,the mechanism underlying the activation function of PCGF6 is poorly ***,we found that PCGF6 co-localizes to gene activation regions along with pluripotency factors such as *** addition,PCGF6 was recruited to a subset of the super-enhancer(SE)regions upstream of cell cycle-associated genes by OCT4,and increased their *** combining with promoter capture Hi-C data,we found that PCGF6 activates cell cycle genes by regulating SE-promoter interactions via 3D *** fin dings highlight a novel mechanism of PcG protein in regulating pluripotency,and provide a research basis for the therapeutic application of pluripotent stem cells.

关键词： PCGF6 Polycomb group super-enhancer 3D chromatin pluripotency

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Interplay of yoga, physical activity, and probiotics in irritable bowel syndrome management: A double-blind randomized study

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Complementary therapies in clinical practice 2024年 57卷 101892页

作者： Wei-Cheng Chao Jen-Chieh Huang San-Land Young Ching-Lin Wu Jui-Chi Shih Lun-De Liao Bill Cheng Ph.D. Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung Taiwan. Division of Gastroenterology Cheng Ching Hospital Chung Kang Branch Taichung Taiwan. Culture Collection & Research Institute Synbio Tech Inc Taiwan. Graduate Institute of Sports and Health Management National Chung Hsing University Taichung Taiwan. Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Miaoli Taiwan. Graduate Institute of Biomedical Engineering National Chung Hsing University Taichung Taiwan. Electronic address: d109001704@mail.nchu.edu.tw.

OBJECTIVES:This study aimed to explore the synergistic impact of online yoga, mindfulness practices, and probiotics on irritable bowel syndrome (IBS) by evaluating changes in physical fitness, mental health, and gut microbiota composition. DESIGN, SETTING AND INTERVENTIONS:The six-week randomized, double-blinded, placebo-controlled trial included 31 IBS patients categorized into three groups: online yoga with probiotics (EP), online yoga with a placebo (EC), and probiotics only (P). Assessments involved physical fitness tests, subjective questionnaires (IBS-QOL, BSRS-5), and gut microbiome analysis. MAIN OUTCOME MEASURES:Participants self-collected stool samples and were given a set of questionnaires at baseline and after six weeks of intervention. Their symptoms were measured by changes in the gut microbiota, physical fitness and quality of life, and psychological well-being. RESULTS:The EP group demonstrated improved cardiovascular endurance (P < 0.001) and a significant reduction in Klebsiella bacterial strains (P < 0.05). Both the EP and EC groups exhibited significantly decreased IBS-QOL scores (P < 0.001 and P < 0.05, respectively), indicating enhanced quality of life. While BSRS-5 scores decreased in both groups, the reduction was statistically insignificant. CONCLUSION:Integrating online yoga, mindfulness practices, and probiotics demonstrated comprehensive benefits for IBS patients. This intervention improved physical fitness and mental well-being and positively influenced gut microbiota composition. The study highlights the potential of this multifaceted approach in managing IBS symptoms and enhancing overall health, emphasizing the relevance of the gut-muscle-brain axis in understanding and addressing IBS complexities. TRIAL REGISTRATION:Taiwanese Registry of Institutional Review Board IRBHP210009/CH11000259.

关键词： Gut-muscle-brain axis IBS Irritable bowel syndrome Physical activity Probiotics Yoga

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Enriched Peripheral Blood-Derived Mononuclear Cells for Treating Knee Osteoarthritis

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Cell transplantation 2023年 32卷

作者： Chang-Han Chuang Chi-Chung Kuo Yueh-Feng Chiang Pei-Yuan Lee Fu-Hui Wang Chia-Ying Hsieh Ching-I Shen Yu-Hsuan Chung Kuan-Der Lee Shih-Fang Wu Hong-Lin Su Chih-Lung Lin Department of Orthopedics Show Chwan Memorial Hospital Changhua Taiwan. PhD Program in Translational Medicine National Chung Hsing University Taichung Taiwan. Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung Taiwan. Department of Neurology Taichung Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Taichung Taiwan. School of Post-Baccalaureate Chinese Medicine Tzu Chi University Hualien Taiwan. Department of Orthopedics Taichung Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Taichung. DuoGenic StemCells Corporation Taichung Taiwan. Department of Medical Research and Cell Therapy and Regenerative Medicine Center Taichung Veterans General Hospital Taichung Taiwan. Department of Medicine and Center for Cell Therapy and Regenerative Medicine College of Medicine Taipei Medical University Taipei City Taiwan. The Joint Program of Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung Taiwan. National Health Research Institutes Taichung Taiwan. Department of Life Sciences National Chung Hsing University Taichung Taiwan. Department of Neurosurgery Asia University Hospital Taichung Taiwan. Department of Occupational Therapy Asia University Taichung Taiwan.

Osteoarthritis (OA) is a common chronic skeletal disease in the elderly. There is no effective therapy to reverse disease severity and knee OA (KOA) progression, particularly at the late stage. This study aims to examine the effect of peripheral blood-derived mononuclear cells (PBMNCs) on pain and motor function rescue in patients with Kellgren-Lawrence (KL) grade II to IV KOA. Participants received one intra-articular (IA) injection of autologous PBMNCs. The mononuclear cells were isolated from peripheral blood, enriched by a specialized medium (MoFi medium), and separated by Ficoll-Paque solution. The isolated and enriched PBMNCs could differentiate into M1 and M2 macrophages . The anti-inflammatory effect of the PBMNCs was similar to that of bone marrow mesenchymal stem cells, evaluated by complete Freund's adjuvant-induced arthritis in rodents. A single-arm and open-label pilot study showed that patients' knee pain and motor dysfunction were significantly attenuated after the cell transplantation, assessed by visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6 and 12 months post-treatment. Notably, the therapeutic effect of the PBMNCs treatment can be stably maintained for 24 months, as revealed by the KOOS scores. These preclinical and pilot clinical data suggest that IA injection of MoFi-PBMNCs might serve as a novel medical technology to control the pain and the progress of KOA.

关键词： macrophages monocytes osteoarthritis peripheral blood mononuclear cells

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Human platelet lysate-cultured adipose-derived stem cell sheets promote angiogenesis and accelerate wound healing via CCL5 modulation

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Stem cell research & therapy 2024年第1期15卷 163页

作者： Yueh-Chen Chen Er-Yuan Chuang Yuan-Kun Tu Chia-Lang Hsu Nai-Chen Cheng Department of Surgery National Taiwan University Hospital and College of Medicine 7 Chung-Shan S. Rd Taipei 100 Taiwan. International Ph.D. Program in Biomedical Engineering Graduate Institute of Biomedical Materials and Tissue Engineering Taipei Medical University Taipei Taiwan. Department of Orthopedics E-Da Hospital/I-Shou University Kaohsiung Taiwan. Department of Medical Research National Taiwan University Hospital Taipei Taiwan. Department of Surgery National Taiwan University Hospital and College of Medicine 7 Chung-Shan S. Rd Taipei 100 Taiwan. nccheng@ntu.edu.tw. Research Center for Developmental Biology and Regenerative Medicine National Taiwan University Taipei Taiwan. nccheng@ntu.edu.tw.

BACKGROUND:A rising population faces challenges with healing-impaired cutaneous wounds, often leading to physical disabilities. Adipose-derived stem cells (ASCs), specifically in the cell sheet format, have emerged as a promising remedy for impaired wound healing. Human platelet lysate (HPL) provides an attractive alternative to fetal bovine serum (FBS) for culturing clinical-grade ASCs. However, the potential of HPL sheets in promoting wound healing has not been fully investigated. This study aimed to explore the anti-fibrotic and pro-angiogenic capabilities of HPL-cultured ASC sheets and delve into the molecular mechanism. METHODS:A rat burn model was utilized to evaluate the efficacy of HPL-cultured ASC sheets in promoting wound healing. ASC sheets were fabricated with HPL, and those with FBS were included for comparison. Various analyses were conducted to assess the impact of HPL sheets on wound healing. Histological examination of wound tissues provided insights into aspects such as wound closure, collagen deposition, and overall tissue regeneration. Immunofluorescence was employed to assess the presence and distribution of transplanted ASCs after treatment. Further in vitro studies were conducted to decipher the specific factors in HPL sheets contributing to angiogenesis. RESULTS:HPL-cultured ASC sheets significantly accelerated wound closure, fostering ample and organized collagen deposition in the neo-dermis. Significantly more retained ASCs were observed in wound tissues treated with HPL sheets compared to the FBS counterparts. Moreover, HPL sheets mitigated macrophage recruitment and decreased subsequent wound tissue fibrosis in vivo. Immunohistochemistry also indicated enhanced angiogenesis in the HPL sheet group. The in vitro analyses showed upregulation of C-C motif chemokine ligand 5 (CCL5) and angiogenin in HPL sheets, including both gene expression and protein secretion. Culturing endothelial cells in the conditioned media compared to media supplemen

关键词： Adipose-derived stem cells Angiogenesis CCL5 Cell sheet Wound healing

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tissue clearing and its applications in neuroscience (vol 21, pg 61, 2020)

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NATURE REVIEWS NEUROSCIENCE 2020年第5期21卷 298-298页

作者： Ueda, Hiroki R. Ertuerk, Ali Chung, Kwanghun Gradinaru, Viviana Chedotal, Alain Tomancak, Pavel Keller, Philipp J. Department of Systems Pharmacology University of Tokyo Tokyo Japan Laboratory for Synthetic Biology RIKEN BDR Suita Japan Institute for Stroke and Dementia Research Klinikum der Universität München Ludwig-Maximilian University of Munich Munich Germany Institute of Tissue Engineering and Regenerative Medicine Helmholtz Zentrum München Neuherberg Germany Munich Cluster for Systems Neurology (SyNergy) Munich Germany Institute for Medical Engineering and Science Massachusetts Institute of Technology Cambridge MA USA Picower Institute for Learning and Memory Massachusetts Institute of Technology Cambridge MA USA Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA USA Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge MA USA Eli & Edythe Broad Institute of MIT and Harvard Cambridge MA USA Center for NanoMedicine Institute for Basic Science Seoul Republic of Korea Graduate Program of Nano Biomedical Engineering Yonsei-IBS Institute Yonsei University Seoul Republic of Korea Division of Biology and Biological Engineering California Institute of Technology Pasadena CA USA Institut de la Vision Sorbonne Université INSERM CNRS Paris France Max Planck Institute of Molecular Cell Biology and Genetics Dresden Germany IT4Innovations Technical University of Ostrava Ostrava Czech Republic Janelia Research Campus Howard Hughes Medical Institute Ashburn VA USA

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

关键词： Immunological techniques Light-sheet microscopy Neuroscience

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Somatic cell reprogramming from different origins and donors into iPSC, with four factors OSKM using viral Sendai vectors

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Stem Cell Research 2025年 86卷 103736页

作者： Desprat, Romain Magnano, Mikael Bensadoun, Paul Soubeyrand, Mathis Callier, Patrick Alle, Quentin Bailly, Anaelle Gantenbein, Benjamin Laagland, Lisanne T. Tryfonidou, Mariana Guicheux, Jerome Camus, Anne Milhavet, Ollivier Lemaitre, Jean-Marc SAFE-iPSC Facility INGESTEM CHU de Montpellier IRMB Montpellier France IRMB Univ Montpellier INSERM Montpellier France Laboratoire de Génétique Chromosomique et Moléculaire plateau technique de Biologie CHU DIJON France Tissue Engineering for Orthopaedics and Mechanobiology Bone and Joint Program Department for BioMedical Research (DBMR) Faculty of Medicine University of Bern Switzerland Department of Orthopaedic Surgery and Traumatology Inselspital Bern University Hospital Medical Faculty University of Bern Freiburgstrasse 3 Bern CH-3010 Switzerland Department of Clinical Sciences Faculty of Veterinary Medicine Utrecht University Utrecht Netherlands Nantes Université Oniris CHU Nantes Inserm Regenerative Medicine and Skeleton RMeS UMR 1229 Nantes 44000 France IRMB Univ Montpellier CNRS Montpellier France

Notocordal-like cells (NLCs) produced from hiPSCs is considered as a promising candidate for cell-based regenerative therapies to treat intervertebral disk degeneration (IVDD). However, OCT4, SOX2, KLF4, C-MYC (OSKM) reprogramming into iPSC was described to maintain (epi)genomic hallmarks of the origin tissue impacting differentiation abilities. In this context, we produced a three donors-derived unique collection of hiPSCs reprogrammed with OSKM, from two cell types, PBMC and Tie2+ nucleus pulposus-progenitor cells (NPPCs). This collection will allow to further evaluate whether the production of NLCs from iPSCs derived from NPPCs or from PBMC would be the most relevant strategy for hiPSC-based IVDD therapy. © 2025 The Author(s)

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Human Papillomavirus Infection is Associated with Increased Risk of Glaucoma: Real-World Evidence

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Ophthalmology 2025年

作者： Wen-Chieh Liao Yu-Jung Su Yun-Feng Li Shao-Wei Lo Chien-Ying Lee Hui-Chin Chang Shuo-Yan Gau Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan Doctoral Program in Tissue Engineering and Regenerative Medicine College of Medicine National Chung Hsing University Taichung Taiwan. Orthopedics Department Chi-Mei Medical Center Tainan Taiwan. School of Medicine Chung Shan Medical University Taichung Taiwan. Harvard T.H. Chan School of Public Health Boston Massachusetts United States. Department of Pharmacology Chung Shan Medical University Taichung Taiwan Department of Pharmacy Chung Shan Medical University Hospital Taichung Taiwan. Orthopedics Department Chi-Mei Medical Center Tainan Taiwan Evidence-based Medicine Center Chung Shan Medical University Hospital Taichung Taiwan Library Chung Shan Medical University Hospital Taichung Taiwan. Department and Graduate Institute of Business Administration National Taiwan University Taipei Taiwan. Electronic address: sixsamurai.shien15@***.

OBJECTIVE:To evaluate the association between human papillomavirus (HPV) infection and the subsequent risk of developing glaucoma using real-world data. DESIGN:Retrospective cohort study. SUBJECTS AND CONTROLS:Adults aged ≥18 years with a diagnosis of HPV were identified from the TriNetX research network and matched 1:1 to individuals without HPV based on demographics, comorbidities, and healthcare utilization patterns. METHODS:Propensity score matching was performed to balance baseline characteristics. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for incident glaucoma. Sensitivity analyses and subgroup stratifications were conducted to assess robustness. MAIN OUTCOME MEASURES:Incident diagnosis of glaucoma, including open-angle and angle-closure subtypes, following HPV infection. RESULTS:Among 451,288 matched participants, HPV infection was associated with an increased risk of glaucoma (HR: 1.34; 95% CI: 1.28-1.41), with elevated risks observed for both open-angle (HR: 1.33; 95% CI: 1.16-1.52) and angle-closure glaucoma (HR: 1.66; 95% CI: 1.20-2.30). The association was more pronounced in older adults, males, and Asians, and further amplified by comorbidities such as hypertension, diabetes, and myopia. Results were consistent across sensitivity analyses. CONCLUSION:HPV infection is associated with a higher risk of glaucoma. While these findings highlight a potential need for increased ophthalmologic surveillance in HPV-positive individuals, the possibility of surveillance bias, in which individuals with HPV may receive more frequent healthcare and eye examinations, cannot be excluded. Further studies are warranted to explore causal mechanisms and control for potential confounding.

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Human Papillomavirus Infection Increases Risk of New-Onset Prurigo Nodularis: A Multi-Center Retrospective Cohort Study Using Global and US Electronic Medical Records of TriNetX network

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Journal of the American Academy of Dermatology 2025年

作者： Shuo-Yan Gau Shao-Wei Lo Yung-Fang Tu Wen-Chieh Liao Yu-Jung Su Hui-Chin Chang Torsten Zuberbier Martin Metz Shiu-Jau Chen Department and Graduate Institute of Business Administration National Taiwan University Taipei Taiwan Evidence-based Medicine Center Chung Shan Medical University Hospital Taichung Taiwan Department of Pharmacology Chung Shan Medical University Taichung Taiwan Harvard T.H. Chan School of Public Health Boston Massachusetts USA Department of Biostatistics Harvard T.H. Chan School of Public Health Boston Massachusetts USA Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan Doctoral Program in Tissue Engineering and Regenerative Medicine College of Medicine Taichung Taiwan Orthopedics Department Chi-Mei Medical Center Tainan Taiwan School of Medicine Chung Shan Medical University Taichung Taiwan Library Chung Shan Medical University Hospital Taichung Taiwan Institute of Allergology Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin Berlin Germany Fraunhofer Institute for Translational Medicine and Pharmacology Immunology and Allergology Berlin Germany Department of Neurosurgery Mackay Memorial Hospital Taipei Taiwan Department of Medicine Mackay Medical College New Taipei City Taiwan

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A microfluidic chip for multiple single-cell interaction analysis 22

A microfluidic chip for multiple single-cell interaction ana...

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22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018

作者： He, Cheng-Kun Chen, Chihchen Hsu, Chia-Hsien Ph.D. Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung Taiwan Institute of NanoEngineering and MicroSystems National Tsing Hua University Hsinchu Taiwan Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Miaoli Taiwan

ISBN: (纸本)9781510897571

The traditional co-culture systems can only be used to describe the population signal, but unable to track individual cells behavior. Our chip demonstrates the ability to high-efficiently capture more than two types of single cells in a large chamber and provide a sufficient culture space useful for studying multiple single cell type interactions. Copyright © (2018) by Chemical and Biological Microsystems Society. All rights reserved.

关键词： Lab-on-a-chip

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Narciclasine suppresses oral cancer metastasis by modulating cathepsin B and extracellular signal-related kinase pathways

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Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2023年 158卷 114159页

作者： Mu-Kuei Shieu Hsin-Yu Ho Chia-Chieh Lin Yu-Sheng Lo Yi-Ching Chuang Ming-Ju Hsieh Mu-Kuan Chen Division of General Practice Department of Medical Education Changhua Christian Hospital Changhua 500 Taiwan. Oral Cancer Research Center Changhua Christian Hospital Changhua 500 Taiwan. Oral Cancer Research Center Changhua Christian Hospital Changhua 500 Taiwan Ph.D. Program in Tissue Engineering and Regenerative Medicine College of Medicine National Chung Hsing University Taichung 402 Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung 404 Taiwan. Electronic address: 170780@cch.org.tw. Department of Otorhinolaryngology Head and Neck Surgery Changhua Christian Hospital Changhua 500 Taiwan. Electronic address: 53780@cch.org.tw.

Oral cancer is a malignancy with unfavorable prognosis due to its high rates of recurrence and lymph node metastasis. Narciclasine is extracted from Narcissus species (Amaryllidaceae), which have antitumor and anti-inflammatory properties. However, the antitumor properties of narciclasine toward oral cancer remain unclear. The present study explored the antimetastatic effects of narciclasine in oral cancer as well as the underlying molecular mechanisms. We treated three oral cancer cell lines with noncytotoxic concentrations of narciclasine and discovered a dose-dependent antimetastatic effect. Mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-related kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), were regulated by narciclasine. We further discovered the ERK pathway to directly affect narciclasine-induced metastasis inhibition by combining treatment with narciclasine and ERK inhibitor. Furthermore, downregulation of cathepsin B (CTSB) in the SAS and SCC-47 cell lines revealed the critical role of CTSB in the antimetastatic effect of narciclasine. Our findings indicate that narciclasine inhibits oral cancer metastasis by regulating the ERK pathway and CTSB. This study provides evidence of the mechanism of narciclasine-induced inhibition oral cancer metastasis and suggests potential targets for use in oral cancer treatment.

关键词： Cathepsin B Metastasis Narciclasine Oral cancer

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