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

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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

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

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

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

Azaphilone and Isocoumarin Derivatives from the Gut Fungus Phaeosphaeria nodorum XZD2-1

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Azaphilone and Isocoumarin Derivatives from the Gut Fungus P...

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

多彩菌物美丽中国——中国菌物学会2019年学术年会

作者： Jiaolu Sun Pinmei Wang haojian zhang Jinzhong Xu Faculty of Marine Biology and Pharmacology Ocean College Zhejiang University

Five new compounds including two azaphilones, lunatoic acids D-E（1, 2）, two isocoumarins,lunatinins B-C（3, 4）, and one α-pyrone derivative, lunatinin D（5）, as well as four known ones, lunatoic acid A（6）,（+）-lunatinin（7）, penicipyran D（8） and chaetoquadrin F（9） were isolated from the rice medium of Phaeosphaeria nodorum XZD2-1. Their planar structures were elucidated by analysis of 1 D and 2 D NMR as well as HRESIMS spectroscopic data. The absolute configurations of compounds 1 and 2 were assigned by experimental and calculated ECD data. Structures of compounds 3-5 were further confirmed by comparing specific rotations with known compounds according to literatures. The Antimicrobial activity and cytotoxicity in vitro against the prostate cancer PC3 cell line were examined.

关键词： azaphilones isocoumarins gut fungus theoretical calculation antimicrobial activity cytotoxicity

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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

Molecular mechanisms for stemness maintenance of acute myeloid leukemia stem cells

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Blood Science 2019年第1期1卷 77-83页

作者： Jiazhen Wang Peipei Wang Tiantian zhang Zhuying Gao Jing Wang Mengdie Feng Rong Yin haojian zhang The State Key Laboratory Breeding Base of Basic Science of Stomatology&Key Laboratory of Oral Biomedicine Ministry of Education School&Hospital of StomatologyWuhan UniversityWuhanChina Frontier Science Center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhanChina

Human acute myeloid leukemia(AML)is a fatal hematologic malignancy characterized with accumulation of myeloid blasts and differentiation *** development of AML is associated with a serial of genetic and epigenetic alterations mainly occurred in hematopoietic stem and progenitor cells(HSPCs),which change HSPC state at the molecular and cellular levels and transform them into leukemia stem cells(LSCs).LSCs play critical roles in leukemia initiation,progression,and relapse,and need to be eradicated to achieve a cure in *** to successfully targeting LSCs is to fully understand the unique cellular and molecular mechanisms for maintaining their ***,we discuss LSCs in AML with a focus on identification of unique biological features of these stem cells to decipher the molecular mechanisms of LSC maintenance.

关键词： Acute myeloid leukemia Leukemia stem cell Maintenance Molecular mechanisms Stemness

拉结钢筋在自保温砌块砌体水平灰缝中埋置长度的试验研究

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新型建筑材料 2017年第10期44卷 66-69,84页

作者：管品武陈萌张豪剑郑州大学土木工程学院河南郑州450002

对自保温砌块砌体水平灰缝进行了钢筋的中心拉拔试验,比较了有水平弯折段和无水平弯折段拉结钢筋在专用砌筑砂浆中的不同受力状况;通过拉结钢筋在自保温砌块砌体中的中心拉拔试验,得出了粘结应力沿埋置长度的变化规律,提出了拉结钢筋在... 详细信息

对自保温砌块砌体水平灰缝进行了钢筋的中心拉拔试验,比较了有水平弯折段和无水平弯折段拉结钢筋在专用砌筑砂浆中的不同受力状况;通过拉结钢筋在自保温砌块砌体中的中心拉拔试验,得出了粘结应力沿埋置长度的变化规律,提出了拉结钢筋在自保温砌块砌体中的埋置长度设计建议。

关键词：自保温砌块拉拔试验锚固长度粘结锚固强度

基于费拉里法的Delta机器人动态目标抓取算法

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华中科技大学学报（自然科学版） 2018年第6期46卷 128-132页

作者：苏婷婷张好剑王云宽秦晓飞中国科学院自动化研究所北京100190 中国科学院大学北京100049 上海理工大学光电信息与计算机工程学院上海200093

针对Delta并联机器人难以在运动环境下有效分拣动态目标的问题,提出了基于费拉里法的动态目标抓取算法.首先,利用3-4-5次多项式运动规律进行了轨迹规划,并对轨迹的不同情况进行了分析.然后,对运动环境下的目标抓取问题建立了数学模型,... 详细信息

针对Delta并联机器人难以在运动环境下有效分拣动态目标的问题,提出了基于费拉里法的动态目标抓取算法.首先,利用3-4-5次多项式运动规律进行了轨迹规划,并对轨迹的不同情况进行了分析.然后,对运动环境下的目标抓取问题建立了数学模型,并针对该数学模型提出了基于费拉里法的动态目标抓取算法.算法测试结果表明：该算法能精准地计算抓取位置,速度快,能满足实时性要求,且无须设置初值,使用便捷.样机实验结果表明：利用该算法能使Delta机器人以90次/min的速度进行动态目标抓取,证明了算法的准确性与稳定性.

关键词： Delta并联机器人轨迹规划动态抓取多项式运动规律费拉里法