1.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
2.Advances in thyroid disorders in children with cancer
Xiaolu JI ; Yao XUE ; Yongjun FANG
International Journal of Pediatrics 2024;51(11):749-752
With the advancement of medical technology,the quality of life of children with cancer is increasingly valued.In particular,the incidence of endocrine disorders is increasing year by year,and thyroid disorders in children with cancer have attracted more and more attention.The main treatment options for cancer are chemotherapy,radiation therapy and surgery.Immunotherapy and hematopoietic stem cell transplantation bring more hope for survival to children with cancer.Although these treatment methods can alleviate the disease,they cannot avoid causing damage to the thyroid gland.Therefore,in order to detect thyroid disorders in a timely manner,thyroid function needs to be monitored during treatment and a standardized follow-up plan needs to be developed.In this article,common thyroid disorders,risk factors and management of thyroid health are discussed.The aim is to improve physicians'understanding of thyroid diseases in children with cancer,detect abnormalities in a timely manner,and intervene to improve their long-term quality of life.
3.Trends in the biological functions and medical applications of extracellular vesicles and analogues.
Yan ZHAO ; Xiaolu LI ; Wenbo ZHANG ; Lanlan YU ; Yang WANG ; Zhun DENG ; Mingwei LIU ; Shanshan MO ; Ruonan WANG ; Jinming ZHAO ; Shuli LIU ; Yun HAO ; Xiangdong WANG ; Tianjiao JI ; Luo ZHANG ; Chenxuan WANG
Acta Pharmaceutica Sinica B 2021;11(8):2114-2135
Natural extracellular vesicles (EVs) play important roles in many life processes such as in the intermolecular transfer of substances and genetic information exchanges. Investigating the origins and working mechanisms of natural EVs may provide an understanding of life activities, especially regarding the occurrence and development of diseases. Additionally, due to their vesicular structure, EVs (in small molecules, nucleic acids, proteins, etc.) could act as efficient drug-delivery carriers. Herein, we describe the sources and biological functions of various EVs, summarize the roles of EVs in disease diagnosis and treatment, and review the application of EVs as drug-delivery carriers. We also assess the challenges and perspectives of EVs in biomedical applications.
4. Progress in the diagnosis and treatment of hereditary nephrolithiasis and/or nephrocalcinosis in children
International Journal of Pediatrics 2019;46(9):652-656
Hereditary nephrolithiasis/nephrocalcinosis in children is a rare disease, the incidence of which is not clear for the time being.Due to the lack of typical symptoms and signs, missed diagnosis, misdiagnosis and delayed diagnosis are very common, some patients have already progressed to end-stage renal disease by the time of definite diagnosis.With the rapid development of molecular diagnostic technology, considerable progress have been made in this kind of disease.This article summarizes the disease classification and recent advances in the diagnosis and treatment of hereditary nephrolithiasis/nephrocalcinosis in children, aiming at improving clinicians′ understanding of this kind of disease and providing help for its early diagnosis and treatment.
5.Enhancement of Aggression Induced by Isolation Rearing is Associated with a Lack of Central Serotonin.
Yiqiong LIU ; Yunong SUN ; Xiaoyan ZHAO ; Ji-Young KIM ; Lu LUO ; Qian WANG ; Xiaolu MENG ; Yonghui LI ; Nan SUI ; Zhou-Feng CHEN ; Chuxiong PAN ; Liang LI ; Yan ZHANG
Neuroscience Bulletin 2019;35(5):841-852
Isolation rearing (IR) enhances aggressive behavior, and the central serotonin (5-hydroxytryptamine, 5-HT) system has been linked to IR-induced aggression. However, whether the alteration of central serotonin is the cause or consequence of enhanced aggression is still unknown. In the present study, using mice deficient in central serotonin Tph2 and Lmx1b, we examined the association between central serotonin and aggression with or without social isolation. We demonstrated that central serotonergic neurons are critical for the enhanced aggression after IR. 5-HT depletion in wild-type mice increased aggression. On the other hand, application of 5-HT in Lmx1b mice inhibited the enhancement of aggression under social isolation conditions. Dopamine was downregulated in Lmx1b mice. Similar to 5-HT, L-DOPA decreased aggression in Lmx1b mice. Our results link the serotoninergic system directly to aggression and this may have clinical implications for aggression-related human conditions.

Result Analysis
Print
Save
E-mail