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Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis

Science Bulletin 2024年第13期69卷 2099-2113页

作者： Jianfei Liang Jing Wang Bingdong Sui Yibo Tong Jihua Chai Qin Zhou Chenxi Zheng Hao Wang Liang Kong haojian zhang Yi Bai State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyTaikang Center for Life and Medical SciencesWuhan UniversityWuhan 430079China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’an 710004China Department of Implant Dentistry College of StomatologyXi’an Jiaotong UniversityXi’an 710004China State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyShaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringSchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyDepartment of Oral and Maxillofacial SurgerySchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China Department of Hematology Zhongnan HospitalWuhan UniversityWuhan 430079China Frontier Science Center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan 430079China Taikang Center for Life and Medical Sciences Wuhan UniversityWuhan 430079China

Stem cells remain in a quiescent state for long-term maintenance and preservation of potency;this process requires fine-tuning regulatory *** this study,we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells(SSCs)in skeletogenesis governed by a key regulator,Ptip(also known as Paxip1,Pax interaction with transcription-activation domain protein-1).Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs,and loss of Ptip in type II collagen(Col2)^(+)progenitors causes abnormal activation and differentiation of SSCs,impaired growth plate morphogenesis,and long bone *** also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1(Pgk1)by repressing histone H3 lysine 27 acetylation(H3K27ac)at the promoter ***,inhibition of glycolysis improved the function of SSCs despite Ptip *** the best of our knowledge,this is the first study to establish an epigenetic framework based on Ptip,which safeguards skeletal stem cell quiescence and potency through metabolic *** framework is expected to improve SSC-based treatments of bone developmental disorders.

关键词： Skeletal stem cells Bone development Epigenetics Ptip Glycolysis

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富血小板纤维蛋白对牙龈成纤维细胞生物学功能的影响

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口腔医学研究 2024年第7期40卷 611-616页

作者：王玉花柴纪华张好建口颌系统重建与再生全国重点实验室口腔生物医学教育部重点实验室口腔医学湖北省重点实验室武汉大学口腔医(学)院湖北武汉430079

目的:探究冷冻干燥富血小板纤维蛋白(freeze-dried platelet-rich fibrin, FD-PRF)对人牙龈成纤维细胞(human gingival fibroblasts, hGFs)功能的影响以及其抗菌性能,为口腔黏膜炎的防治提供新思路。方法:采用流式细胞术、CCK-8检测细... 详细信息

目的:探究冷冻干燥富血小板纤维蛋白(freeze-dried platelet-rich fibrin, FD-PRF)对人牙龈成纤维细胞(human gingival fibroblasts, hGFs)功能的影响以及其抗菌性能,为口腔黏膜炎的防治提供新思路。方法:采用流式细胞术、CCK-8检测细胞增殖(cell counting kit-8,CCK-8)、细胞划痕和Transwell实验,检测FD-PRF对hGFs细胞周期、增殖和迁移的影响;采用倾注平板法和振荡培养法研究FD-PRF的抗菌作用。结果:CCK-8实验结果表明,随着FD-PRF浓度升高,hGFs的细胞数量显著增加。细胞周期结果显示,S-G2/M期的细胞比例:5%FD-PRF组>1%FD-PRF组>对照组,而G0-G1期细胞则相反。迁移实验结果显示,FD-PRF显著提升了hGFs的迁移速度。抗菌实验结果显示,FD-PRF组相比于对照组的大肠杆菌和金黄色葡萄球菌数量明显减少。结论:FD-PRF促进hGFs进入细胞分裂期,进而促进细胞增殖。FD-PRF促进hGFs迁移。此外,本研究还证实FD-PRF具有一定的抗菌性。提示FD-PRF可以促进口腔黏膜炎的愈合。

关键词：冷冻干燥富血小板纤维蛋白成纤维细胞抗菌性口腔黏膜炎

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Mettl3依赖的m^(6)A甲基化调控CD8^(+)T细胞效应分化和记忆形成

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Science Bulletin 2024年第1期69卷 82-96页

作者：郭文慧王昭张雅娇李亚书杜倩张田田胡瑾姚英鹏张家睿徐迎弟崔晓孙振游孟昊余国涛张好建杜旭光徐靖宇于舒洋 State Key Laboratory of Animal Biotech Breeding College of Biological SciencesChina Agricultural UniversityBeijing 100193China Frontier Science Center for Immunology and Metabolism Medical Research InstituteSchool of MedicineWuhan UniversityWuhan 430071China The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University Zunyi 563000China

Efficient immune responses rely on the proper differentiation of CD8^(+)T cells into effector and memory ***,we show a critical requirement of N^6-Methyladenosine(m^(6)A)methyltransferase Mettl3 during CD8^(+)T cell responses upon acute viral *** deletion of Mettl3 in CD8^(+)T cells impairs effector expansion and terminal differentiation in an m^(6)A-dependent manner,subsequently affecting memory formation and the secondary response of CD8^(+)T *** combined RNA-seq and m^(6)AmiCLIP-seq analyses reveal that Mettl3 deficiency broadly impacts the expression of cell cycle and transcriptional ***,Mettl3 binds to the Tbx21 transcript and stabilizes it,promoting effector differentiation of CD8^(+)T ***,ectopic expression of T-bet partially restores the defects in CD8^(+)T cell differentiation in the absence of ***,our study highlights the role of Mettl3 in regulating multiple target genes in an m^(6)A-dependent manner and underscores the importance of m^(6)A modification during CD8^(+)T cell response.

关键词： CD8^(+)T cell T cell response Mettl3 m^(6)A Effector Memory

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从“浊伏肺络”论治肺结节

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天津中医药 2024年第8期41卷 980-983页

作者：张淑芮程闻廖冬颖张豪健贾英杰天津中医药大学第一附属医院天津300381 国家中医针灸临床医学研究中心天津300381 天津中医药大学天津301617

总结探讨从“浊伏肺络”论治肺结节。认为肺结节病的诊疗当从宏观处出发,在认识肺结节病核心病机的基础上以辨病论治为主。总结出以肺络为病位,浊邪为病理因素,气血津液代谢异常为基本病机,“浊伏肺络”为核心病机,“黜浊散结”为治则... 详细信息

总结探讨从“浊伏肺络”论治肺结节。认为肺结节病的诊疗当从宏观处出发,在认识肺结节病核心病机的基础上以辨病论治为主。总结出以肺络为病位,浊邪为病理因素,气血津液代谢异常为基本病机,“浊伏肺络”为核心病机,“黜浊散结”为治则的肺结节病中医诊疗思路。以此为基础,根据浊邪特点与临床表现具体运用化痰祛浊、解毒清浊、化瘀散浊、散结化浊、旺气磨积5种治法,以期在较长的观察等待期达到拔本塞源、消散结节的目的。

关键词：肺结节浊邪黜浊散结

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RNA m^(6) A modification: Mapping methods, roles, and mechanisms in acute myeloid leukemia

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Blood Science 2022年第3期4卷 116-124页

作者： Rong Yin Yashu Li Wen Tian Fuling Zhou haojian zhang Department of Hematology Zhongnan HospitalWuhan UniversityWuhanPeople’s Republic of China Frontier Science Center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhanPeople’s Republic of China

N^(6)-Methyladenosine(m^(6)A)is the most abundant modification in eukaryotic mRNA,and plays important biological functions via regulating RNA fate *** studies have shown that m^(6)A modification plays a key role in hematologic malignancies,including acute myeloid *** current growth of epitranscriptomic research mainly benefits from technological progress in detecting RNA m^(6)A modification in a transcriptome-wide *** this review,we first briefly summarize the latest advances in RNA m^(6)A biology by focusing on writers,readers,and erasers of m^(6)A modification,and describe the development of high-throughput methods for RNA m^(6)A *** further discuss the important roles of m^(6)A modifiers in acute myeloid leukemia,and highlight the identification of potential inhibitors for AML treatment by targeting of m^(6)A ***,this review provides a comprehensive summary of RNA m^(6)A biology in acute myeloid leukemia.

关键词： Acute myeloid leukemia Mapping RNA m^(6)A modification

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Berberine ameliorates chronic kidney disease through inhibiting the production of gut-derived uremic toxins in the gut microbiota

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1537-1553页

作者： Libin Pan Hang Yu Jie Fu Jiachun Hu Hui Xu Zhengwei zhang Mengmeng Bu Xinyu Yang haojian zhang Jinyue Lu Jiandong Jiang Yan Wang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences/Peking Union Medical CollegeBeijing 100050China Received 5 September 2022Revised 8 November

At present,clinical interventions for chronic kidney disease are very limited,and most patients rely on dialysis to sustain their lives for a long ***,studies on the gut—kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney *** study showed that berberine,a natural drug with low oral availability,significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins,including ***,berberine reduced the content of pcresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine—p-cresol pathway of the intestinal ***,berberine increased the butyric acid producing bacteria and the butyric acid content in feces,while decreased the renal toxic trimethylamine *** findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut—kidney axis.

关键词： Chronic kidney disease Gut microbiota Berberine Gut—kidney axis Clostridium p-Cresol Uremic toxins p-Cresol sulfate

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Molecular mechanisms for survival regulation of chronic myeloid leukemia stem cells

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Protein & Cell 2013年第3期4卷 186-196页

作者： haojian zhang Shaoguang Li Division of Hematology/Oncology Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterMA 01605USA

Studies on chronic myeloid leukemia(CML)have served as a paradigm for cancer research and *** studies involve the identifi cation of the fi rst cancer-associated chromosomal abnormality and the subsequent development of tyrosine kinase inhibitors(TKIs)that inhibit BCR-ABL kinase activity in *** becomes clear that leukemia stem cells(LSCs)in CML which are resistant to TKIs,and eradication of LSCs appears to be extremely ***,one of the major issues in current CML biology is to understand the biology of LSCs and to investigate why LSCs are insensitive to TKI monotherapy for developing curative therapeutic *** from our group and others have revealed that CML LSCs form a hierarchy similar to that seen in normal hematopoiesis,in which a rare stem cell population with limitless self-renewal potential gives rise to progenies that lack such *** also possess biological features that are different from those of normal hematopoietic stem cells(HSCs)and are critical for their malignant *** this review,we summarize the latest progress in CML field,and attempt to understand the molecular mechanisms of survival regulation of LSCs.

关键词： molecular mechanisms chronic myeloid leukemia leukemia stem cell

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Gut microbiota-based pharmacokinetic-pharmacodynamic study and molecular mechanism of specnuezhenide in the treatment of colorectal cancer targeting carboxylesterase

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Journal of Pharmaceutical Analysis 2023年第9期13卷 1024-1040页

作者： Hang Yu Hui Xu Xinyu Yang Zhengwei zhang Jiachun Hu Jinyue Lu Jie Fu Mengmeng Bu haojian zhang Zhao Zhai Jingyue Wang Jiandong Jiang Yan Wang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences/Peking Union Medical CollegeBeijing100050China

Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has antiinflammation,anti-oxidation,and anti-tumor *** low bioavailability makes it difficult to explain the mechanism of pharmacological effect of *** this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were *** can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were *** addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its *** the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of *** addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut ***,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor *** the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of ***,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in *** the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.

关键词： Specnuezhenide Pharmacokinetics Tumor Gut microbiota Fungi Metabolism

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Chinese herbal medicines for prostate cancer therapy: From experimental research to clinical practice

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Chinese Herbal Medicines 2023年第4期15卷 485-495页

作者： Fanming Kong Chaoran Wang Jing zhang Xiaoqun Wang Binxu Sun Xian Xiao haojian zhang Yanqi Song Yingjie Jia Department of Oncology First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300381China National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion Tianjin 300381China Graduate School Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Traditional Chinese Medicine Tianjin Medical University General HospitalTianjin 300052China

Prostate cancer remains the second most common malignancy in men worldwide, is a global health issue,and poses a huge health burden. Precision medicine provides more treatment options for prostate cancer patients, but its popularity, drug resistance, and adverse reactions still need to be focused on. Chinese herbal medicines(CHMs) have been widely accepted as an alternative therapy for cancer, with the advantages of multiple targets, multiple pathways, and low toxicity. We searched the experimental research and clinical practice of CHMs for prostate cancer treatment published in Pub Med, Embase, and Web of Science in the last five years. We found five CHM formulas and six single CHM extracts as well as 12 CHM-derived compounds, which showed induction of apoptosis, autophagy, and cell cycle arrest, suppression of angiogenesis, proliferation, and migration of prostate cancer cells, reversal of drug resistance,and enhancement of anti-tumor immunity. The mechanisms of action include the PI3K/Akt/mTOR, AR,EGFR and Wnt/β-catenin signaling pathways, which are commonly implicated in the development of prostate cancer. We also summarized the advantages of CHMs in patients with hormone-sensitive and castration-resistant prostate cancer and provided ideas for their further experimental design and application.

关键词： Chinese herbal medicines clinical practice experimental research prostate cancer review

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贾英杰“黜浊培本”辨治肝癌经验

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中医学报 2024年第1期39卷 140-143页

作者：廖冬颖刘家宇徐竞一张豪健张淑芮王晓群孙彬栩孔凡铭贾英杰天津中医药大学第一附属医院/国家中医针灸临床医学研究中心天津300381 天津中医药大学天津301617

贾英杰认为,肝癌患者“气郁”为先,“本虚”继或兼之,“虚、毒、瘀”久羁为患,变生“癌浊”,发为癌瘤,具有“始于肝,传于脾,终于肾”之传变规律,呈癌浊丛生、弥散肝络、实邪盘踞、气血逆乱之象。临证强调“分阶段辨治”,早期重在泻火达... 详细信息

贾英杰认为,肝癌患者“气郁”为先,“本虚”继或兼之,“虚、毒、瘀”久羁为患,变生“癌浊”,发为癌瘤,具有“始于肝,传于脾,终于肾”之传变规律,呈癌浊丛生、弥散肝络、实邪盘踞、气血逆乱之象。临证强调“分阶段辨治”,早期重在泻火达木、黜浊散毒以罢邪;中期著于健脾平木、护土安中以调补;晚期贵在滋水涵木、培本固元以维稳。贾师承先贤之理法,合今时“黜浊培本”治肝癌之新,旨在达阴阳五行、五脏六腑、气血营卫之“平期”,为肝癌辨治提供经验和思路。

关键词：肝癌黜浊培本贾英杰

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