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Inhibition of KDM6B prevents osteoarthritis by blocking growth plate-like H3K27me3 loss in bivalent genes

Science China Life Sciences 2025年第5期68卷 1423-1436页

作者： Hao Du Yao Zhang Xi Yu Xuanhe You Diwei Wu Ze Du Yongrui Cai Zhenyu Luo Hanpeng Lu Zhixin Liao Bi-Sen Ding Ya Zhao Yan Wang Ke Xiao Fan Yang Fangji Gan Ning Ning Jiancheng Zeng Peiliang Shi Zongke Zhou Shishu Huang Department of Orthopedic Surgery and Orthopedic Research Institute West China HospitalSichuan University Rehabilitation Medicine Center West China HospitalSichuan University Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan University Institute of Translational Medicine Medical CollegeYangzhou University Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research College of Animal Science and Technology Sichuan Agricultural University Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province Sichuan Agricultural University Department of Lower Limb Surgery of Sichuan Province Orthopedic Hospital Central Laboratory of Sichuan Province Orthopedic Hospital Brain Cognition and Brain Disease Institute (BCBDI) Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences (CAS)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions School of Mechanical Engineering Sichuan University Gem Pharmatech (Chengdu) Co. Ltd.

Osteoarthritis(OA) is the most prevalent joint disorder occurring with articular cartilage degradation. It includes a switch from an articular to a growth plate chondrocyte phenotype. Here, we investigated the histone modification profiles and found significant H3K27me3 loss in OA, which led to disease-associated gene expression. Surprisingly, these genes were occupied by both H3K27me3 and H3K4me3 in normal chondrocytes, showing a poised bivalent state. Furthermore, we observed the derepression of similar bivalent genes in growth plate chondrocytes. Finally, a KDM6B inhibitor GSK-J4 prevented the H3K27me3 loss and cartilage damage in the rat OA model. Our results reveal an inherited bivalent epigenetic signature on developmental genes that makes articular chondrocytes prone to hypertrophy and contributes to a promising epigenetic therapy for OA.

关键词： osteoarthritis histone modifications H3K27me3 bivalency growth plate

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Chromosome instability functions as a potential therapeutic reference by enhancing chemosensitivity to BCL-XL inhibitors in colorectal carcinoma

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中国药理学报（英文版） 2024年第11期45卷 2420-2431页

作者： Xiao Fang Wen-ying Yu Chun-miao Zhu Nan Zhao Wei Zhao Ting-ting Xie Li-jie Wei Xi-ran Sun Juan Xie Ya Zhao Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001China Clinical Medical College Yangzhou UniversityYangzhou 225009China Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research Yangzhou 225001China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001China Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research Yangzhou 225001China

Chromosome instability(CIN)and subsequent aneuploidy are prevalent in various human malignancies,influencing tumor progression such as metastases and *** studies demonstrate the development of chemoresistance in high-CIN tumors,which poses significant therapeutic *** the association of CIN with poorer prognosis and suppressed immune microenvironment observed in colorectal carcinoma(CRC),here we aimed to discover chemotherapeutic drugs exhibiting increased inhibition against high-CIN CRC *** using machine learning methods,we screened out two BCL-XL inhibitors Navitoclax and WEHI-539 as CIN-sensitive reagents in *** analyses using a CIN-aneuploidy cell model confirmed the vulnerability of high-CIN CRC cells to these *** further revealed the critical role of BCL-XL in the viability of high-CIN CRC *** addition,to ease the evaluation of CIN levels in clinic,we developed a three-gene signature as a CIN surrogate to predict prognosis,chemotherapeutic and immune responses in CRC *** results demonstrate the potential value of CIN as a therapeutic target in CRC treatment and the importance of BCL-XL in regulating survival of high-CIN CRC cells,therefore representing a valuable attempt to translate a common trait of heterogeneous tumor cells into an effective therapeutic target.

关键词： colorectal carcinoma chromosome instability chemosensitivity BCL-XL Navitoclax WEHI-539

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Peroxisome proliferator-activated receptors as biomarkers in cerebrovascular diseases: A narrative review

NeuroMarkers

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NeuroMarkers 2025年第1期2卷

作者： Xiangyi Xu Qianqian Chen Shun Li Tianqing Xiong Institute of Translational Medicine Medical College Yangzhou University Yangzhou Jiangsu Province China Department of Neurology University of Pittsburgh School of Medicine Pittsburgh PA USA Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research Yangzhou University Yangzhou Jiangsu Province China

Cerebrovascular disease, a critical global health challenge, profoundly affects the quality and longevity of human life due to its alarmingly high incidence, disability, mortality, recurrence rate, and extensive complications. The underlying risk factors, particularly the combined effects of hypertension, hyperlipidemia, and hyperglycemia, exacerbate this disease burden. Recent breakthroughs have highlighted the role of biomarkers, specifically peroxisome proliferator-activated receptors, as a member of the nuclear transcription factor family, in regulating essential physiological and pathological processes, including fat metabolism, inflammation, cancer progression, neurodegeneration, and cardiovascular health. This paper reviews the role of peroxisome proliferator-activated receptors (PPARs) in cerebrovascular disease and its associated risk factors. It focuses on the three core members of the PPAR family—PPARα, PPARβ/δ, and PPARγ—which play a crucial role in regulating the complex network of cerebrovascular diseases and their associated risk factors. These three PPAR isoforms not only regulate the balance and distribution of lipids in the body by finely tuning various aspects of fat metabolism, but also modulate key physiological and pathological processes, including inflammatory responses, cell proliferation, and differentiation. The mechanisms by which PPARs operate are both complex and subtle, and their widespread influence makes them potential bridges between basic research and clinical practice. Developing targeted interventions for PPARs to enable precision medicine and personalized management of cerebrovascular diseases could provide more effective, safer, and tailored treatment options for patients with these conditions.

关键词： Biomarker Cerebrovascular disease Nuclear transcription factor Peroxisome proliferator-activated receptor α Precision medicine

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Vitamin B2 functionalized iron oxide nanozymes for mouth ulcer healing

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Science China(Life Sciences) 2020年第1期63卷 68-79页

作者： Yunhao Gu Yixin Huang Zhiyue Qiu Zhuobin Xu Dandan Li Lei Chen Jing Jiang Lizeng Gao Institute of Translational Medicine Department of PharmacologySchool of MedicineYangzhou UniversityYangzhou 225001China Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research Yangzhou UniversityYangzhou 225001China

Mouth ulcer is associated with inflammation and high risk of bacterial infection, which aggravates the patient's ***, there is no effective treatment for mouth ulcer. Herein, we report that vitamin-modified iron oxide nanoparticles improve the healing of mouth ulcer through anti-inflammation and antibacterial activities. We discovered that vitamin B2(VB2)modified iron oxide nanoparticles performed enhanced peroxidase-like, catalase-like, and superoxide dismutase(SOD)-like activities, acting as typical iron oxide nanozymes(IONzymes) with triad activities. In particular, VB2 modification significantly improved the SOD-like activity, thus providing a reactive oxygen species(ROS)-scavenging ability. Cellular antioxidant experiments showed that vitamin B2 modified IONzymes(VB2-IONzymes) protect human oral keratinocytes(HOK) and BALB/3 T3 cells from hydrogen peroxide(H2O2), and these cells have high biocompatibility to eukaryotic cells. In addition, VB2-IONzymes exerted an antibacterial activity against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. Importantly, VB2-IONzymes accelerated the recovery of mouth ulcer and reduced the local secretion of inflammatory factors in mouse ulcer model via ROS scavenging and antibacterial activity. Taken together, our work demonstrates that vitamin B2 modification endows iron oxide nanoparticles with enhanced enzyme-like activities and VB2-IONzymes may be a promising reagent in the treatment of mouth ulcer because of their intrinsic anti-inflammation and antibacterial capabilities.

关键词： iron oxide nanozymes vitamin B2 ROS scavenging mouth ulcer anti-inflammation

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Prognostic SLC family genes promote cell proliferation,migration,and invasion in hepatocellular carcinoma

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生物化学与生物物理学报（英文版） 2021年第8期53卷 1065-1075页

作者： Xiao Fang Ying Liu Wangwen Xiao Nan Zhao Chunmiao Zhu Duonan yu Ya Zhao Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research Medical CollegeYangzhou UniversityYangzhou 225009China Clinical Medical College Yangzhou UniversityYangzhou 225009China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225009China Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis Medical CollegeYangzhou UniversityYangzhou 225009China Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research Medical CollegeYangzhou UniversityYangzhou 225009China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225009China Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research Medical CollegeYangzhou UniversityYangzhou 225009China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225009China Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis Medical CollegeYangzhou UniversityYangzhou 225009China

The solute carrier (SLC) superfamily genes encode more than 300 members that are responsible for the transmembrane transportation of many essential endogenous and exogenous compounds ranging from nutrients to *** are highly expressed in metabolic organs such as the liver,regulating the homeostasis of metabolites and the disposition of *** contrast to their well-studied roles in physiological and pharmacological processes,little is known about the relationship between SLCs and cancer ***,we aimed to explore the potential role of SLCs in progression and prognosis of hepatocellular carcinoma (HCC),one of the most commonly diag-nosed cancers and leading causes of death *** performing bioinformatics analyses of HCC dataset from The Cancer Genome Atlas database,we identified three novel signature SLCs(SLC51B,SLC22A15,and SLC2A1) that are indicative of poor *** functional analyses suggested the potential regulation of the three prognostic SLCs on cell proliferation and *** knockdown experiments performed in HCC cell lines showed that all three prognostic SLCs positively regulated the proliferation of HCC cells,among which SLC22A 15 and SLC2A 1 were required for migration and invasion of the cells,demonstrating remarkable consistency with the roles identified by bioinformatics methods in ***,our study provides a novel prognos-tic biomarker for HCC and reveals the significant roles of SLCs in HCC progression,which might have been undervalued in the past.

关键词： hepatocellular carcinoma prognostic signature SLC family genes proliferation metastasis

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Dual Fluorescent Protein(yEGFP/DsRed-Express-2) Bioassay System for Rapid Screening for Chemical Mutagens Based on RNR3 Regulation in Saccharomyces Cerevisiae

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Biomedical and Environmental Sciences 2021年第5期34卷 421-424页

作者： LIU Xing CHEN Geng LU Gang Yu YAO Jia ZHU Fang Yu XU Jun LI Xiang Ming Preventive Medicine Department of Yangzhou Medical College Yangzhou UniversityYangzhou 225001JiangsuChina Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001JiangsuChina Institute of Toxicology and Risk Assessment Jiangsu Provincial Center for Disease Control and PreventionNanjing 210009JiangsuChina Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research Yangzhou 225001JiangsuChina

Over the past several years,the most widely used in vitro tests for mutagenicity have been those performed on *** include the Ames test,SOS,and SOS/umu chromotest[1,2].The Ames test is the most commonly used system,bu... 详细信息

关键词： SOS/umu automata Ames

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MiR-144/451 in hematopoiesis and beyond

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Exrna 2019年第April-May-June期1卷 1-12页

作者： Wang, Ting Wu, Fan Yu, Duonan Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research Yangzhou University School of Medicine Yangzhou China Institute of Translational Medicine Yangzhou University School of Medicine Yangzhou China Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis Yangzhou China

Micrornas (mirnas), a class of 18–25 nucleotide (nt) non-coding rnas, usually inhibit the expression of their target genes. They are transcribed from endogenous genes and are processed for maturation by multiple pathways. miR-144/451, a bicistronic gene locus, encodes miR-144 and miR-451, both of which are highly conserved in evolution. These two mirnas are on the same primary rna molecule whose transcription is controlled by multiple nuclear proteins, including GATA1, GATA4, Myc, Oct1, Pax4, FXR, AP1, SMAD3 and SMAD4 depending on tissue types. They are abundant and almost exclusively exist in red blood cells, but low expression of both miR-144 and miR-451 are also detected in non-erythroid lineages. Interestingly, deletion of both miR-144 and miR-451 DNA sequences coding pre-miR-144/451 hairpins in mice leads only mild microcytic anemia but worsen upon a number of stresses including developmental stress, acute blood loss, phenohydrazine-induced hemolysis and precursor depletion by chemotherapeutic drug 5-FU. Such knockout animals older than 15 months also spontaneously develop malignant tumors including B-lymphoma and acute myeloid leukemia, indicating that miR-144/451 is a bona fide tumor-suppressing gene in non-erythroid cells, though its levels are much lower compared to that in red blood cells. Consistent with the findings in animals, disruption of miR-144/451 expression and their abnormal functions are observed in human hematopoietic and non-hematopoietic organs. Moreover, miR-451 is the only mirna discovered so far whose maturation does not depend on Dicer, an enzyme required by all other mirnas for maturation. This review focuses on the biogenesis, transcriptional regulation and biological roles of miR-144/451 in erythropoiesis, tumor initiation and other pathological conditions. © The Author(s).

关键词： Biogenesis Cancer Erythropoiesis MiR-144 MiR-451 Transcription

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Unlocking epigenetics for precision treatment of Ewing’s sarcoma

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Chinese Journal of Cancer research 2024年第3期36卷 322-340页

作者： Zhehao Fan Shuangshuang Dong Ning Wang Muhammad Babar Khawar Jingcheng Wang Haibo Sun Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001China Jiangsu Key Laboratory of Experimental&Translational Non-Coding RNA Research Yangzhou 225001China Department of Pathology Northern Jiangsu People’s Hospital Affiliated to Yangzhou University/Clinical Medical CollegeYangzhou UniversityYangzhou 225001China Department of Orthopedics Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityYangzhou 225001China

Ewing’s sarcoma(EWS)is a highly aggressive malignant bone tumor primarily affecting adolescents and young *** the efficacy of chemoradiotherapy in some cases,the cure rate for patients with metastatic and recurrent disease remains ***,there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS *** regulation,a crucial factor in physiological processes,plays a significant role in controlling cell proliferation,maintaining gene integrity,and regulating *** studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS.A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug *** review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS,integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.

关键词： Ewing’s sarcoma epigenetic targets drug resistance drug development

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Mini-organs with big impact:Organoids in liver cancer studies

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Oncology research 2023年第5期31卷 677-688页

作者： MUHAMMAD BABAR KHAWAR YAJUN WANG ANEEQA MAJEED ALI AFZAL KABEER HANEEF HAIBO SUN Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhouChina Jiangsu Key Laboratory of Experimental and Translational Non-Coding RNA Research YangzhouChina Applied Molecular Biology and Biomedicine Lab Department of ZoologyUniversity of NarowalNarowalPakistan Department of Oncology Haian Hospital of Traditional Chinese MedicineHaianChina Molecular Medicine and Cancer Therapeutics Lab Department of ZoologyFaculty of Sciences TechnologyUniversity of Central PunjabLahorePakistan Chinese Institute for Brain Research(CIBR) BeijingChina

Hepatocellular carcinoma,the most common primary liver cancer and a leading cause of death,is a difficult disease to treat due to its heterogeneous *** models,such as 2D culture and patient-derived xenografts,have not proven ***,the development of 3D culture techniques,such as organoids,which can mimic the tumor microenvironment(TME)and preserve heterogeneity and pathophysiological properties of tumor cells,offers new opportunities for treatment and *** also have the potential for biomarker detection and personalized medication,as well as genome editing using CRISPR/Cas9 to study the behavior of certain genes and therapeutic *** review explores to-the-date development of organoids with a focus on TME modeling in 3D organoid ***,it discusses gene editing using CRISPR/Cas9 in organoids,the challenges faced,and the prospects in the field of organoids.

关键词： Heterogeneity Tumor Organoid Liver Treatment Therapy

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Importance of accurate diagnosis of congenital agenesis of the gallbladder from atypical gallbladder stone presentations:A case report

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World Journal of Clinical Cases 2023年第28期11卷 6864-6870页

作者： Hai-Jian Sun Fei Ge Yue Si Zheng Wang Hai-Bo Sun Department of General Surgery Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina Department of Gastroenterology Haian Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNantong 226600Jiangsu ProvinceChina Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225000Jiangsu ProvinceChina Jiangsu Key Laboratory of Experimental&Translational Non-Coding RNA Research Yangzhou Yangzhou UniversityYangzhou 225000Jiangsu ProvinceChina Department of Endocrinology The Affiliated Hospital of Yangzhou UniversityYangzhou 225000Jiangsu ProvinceChina

BACKGROUND Congenital agenesis of the gallbladder(CAGB)is a rare condition often misdiagnosed as cholecystolithiasis,leading to unnecessary *** diagnosis and surgical exploration are crucial in patients with suspected CAGB or atypical gallbladder stone *** imaging,such as magnetic resonance cholangiopancreatography(MRCP),plays a vital role in confirming the *** intraoperative dissection is necessary to avoid iatrogenic injuries and *** consultations and collaboration,along with the use of various diagnostic methods,can minimize associated *** SUMMARY We present the case of a 34-year-old female with suspected gallbladder stones,ultimately diagnosed with CAGB through surgical *** patient underwent laparoscopic examination followed by open exploratory surgery,which confirmed absence of the *** imaging studies supported the *** patient received appropriate postoperative care and experienced a successful *** This case highlights the rarity of CAGB and the importance of considering this condition in the differential diagnosis of patients with gallbladder stone *** diagnosis using preoperative imaging,such as MRCP,is crucial to prevent unnecessary *** should exercise caution and conduct meticulous dissection during surgery to avoid iatrogenic injuries and ensure accurate *** collaboration and utilization of various diagnostic methods are essential to minimize the risk of *** of the optimal treatment strategy should prioritize minimizing trauma and maintaining open communication with the patient and their family members.

关键词： Congenital agenesis of the gallbladder Absent gallbladder Biliary tract anomalies Case report

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