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ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/-catenin signaling

《医学前沿（英文）》 2023年 第17卷 第4期   页码 685-698 doi: 10.1007/s11684-022-0942-1

摘要： Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.

关键词： acute myeloid leukemia     acyl-CoA synthetase long chain family member 5     Wnt3a     palmitoylation     ABT-199    

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Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling

null

《医学前沿（英文）》 2015年 第9卷 第4期   页码 444-456 doi: 10.1007/s11684-015-0421-z

摘要：

Ventricular hypertrophy is a powerful and independent predictor of cardiovascular morbid events. The vascular properties of low-dose acetyl salicylic acid (aspirin) provide cardiovascular benefits through the irreversible inhibition of platelet cyclooxygenase 1; however, the possible anti-hypertrophic properties and potential mechanism of aspirin have not been investigated in detail. In this study, healthy wild-type male mice were randomly divided into three groups and subjected to transverse aortic constriction (TAC) or sham operation. The TAC-operated mice were treated with the human equivalent of low-dose aspirin (10 mg·kg−1·d−1); the remaining mice received an equal amount of phosphate buffered saline with 0.65% ethanol, which was used as a vehicle. A cardiomyocyte hypertrophy model induced by angiotensin II (10 nmol·L−1) was treated with the human equivalent of low (10 or 100 µmol·L−1) and high (1000 µmol·L−1) aspirin concentrations in plasma. Changes in the cardiac structure and function were assessed through echocardiography and transmission electron microscopy. Gene expression was determined through RT-PCR and western blot analysis. Results indicated that aspirin treatment abrogated the increased thickness of the left ventricular anterior and posterior walls, the swelling of mitochondria, and the increased surface area in in vivo and in vitro hypertrophy models. Aspirin also normalized the upregulated hypertrophic biomarkers, β-myosin heavy chain (β-MHC), atrial natriuretic peptide (ANP), and b-type natriuretic peptide (BNP). Aspirin efficiently reversed the upregulation of β-catenin and P-Akt expression and the TAC- or ANG II-induced downregulation of GSK-3β. Therefore, low-dose aspirin possesses significant anti-hypertrophic properties at clinically relevant concentrations for anti-thrombotic therapy. The downregulation of β-catenin and Akt may be the underlying signaling mechanism of the effects of aspirin.

关键词： aspirin     Akt     cardiac hypertrophy     GSK-3β     Wnt/β-catenin    

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Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea

null

《医学前沿（英文）》 2016年 第10卷 第3期   页码 237-249 doi: 10.1007/s11684-016-0464-9

摘要：

Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals possess limited regenerative capacity because of the active participation of various signaling pathways, including Wnt and Notch signaling. The Wnt and Notch pathways are highly sophisticated and conserved signaling pathways that control multiple cellular events necessary for the formation of sensory hair cells. Both signaling pathways allow resident supporting cells to regenerate hair cells in the neonatal cochlea. In this regard, Wnt and Notch signaling has gained increased research attention in hair cell regeneration. This review presents the current understanding of the Wnt and Notch signaling pathways in the auditory portion of the inner ear and discusses the possibilities of controlling these pathways with the hair cell fate determiner Atoh1 to regulate hair cell regeneration in the mammalian cochlea.

关键词： inner ear     cochlea     hair cell     regeneration     Wnt     Notch     signaling pathways    

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Unidirectional and stage-dependent roles of Notch1 in Wnt-responsive Lgr5

Hui Jiang, Shan Zeng, Wenli Ni, Yan Chen, Wenyan Li

《医学前沿（英文）》 2019年 第13卷 第6期   页码 705-712 doi: 10.1007/s11684-019-0703-y

摘要： Wnt and Notch signaling play crucial roles in the determination of the prosensory domain and in the differentiation of hair cells (HCs) and supporting cells during mouse inner ear development; however, the relationship between the two signaling pathways in the mouse cochlea remains largely unknown. Here, we investigated the interactions between Notch and Wnt signaling on the basis of the bidirectional regulation of Notch1 specifically in Wnt-responsive Lgr5 progenitors during different cochlear development stages. We found that the downregulation of Notch1 in Lgr5 cells from embryonic day (E) 14.5 to E18.5 can drive the quiescent Lgr5 cells to re-enter the cell cycle and differentiate into extra HCs, whereas the upregulation of Notch1 expression did not affect the proliferation or differentiation of otic progenitor cells. No effect was observed on the upregulation or downregulation of Notch1 in Lgr5 cells from E10.5 to E14.5. We concluded that the roles of Notch1 in Wnt-responsive Lgr5 cells are unidirectional and stage dependent and Notch1 serves as a negative regulator for Lgr5 progenitor activation during cochlear differentiation. Our findings improved the understanding of the interactions between Notch and Wnt signaling in cochlear development.

关键词： inner ear     cochlear     Wnt     Notch     Lgr5     auditory system    

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Wnt/β-catenin signaling pathway and its role in hepatocellular carcinoma

ZHANG Xufeng, YU Liang, LU Yi

《医学前沿（英文）》 2008年 第2卷 第3期   页码 216-228 doi: 10.1007/s11684-008-0042-x

摘要： Wnt/?-catenin signaling pathway has been identified as a key cellular pathway in embryogenesis and disease, including cancers. In recent years, more and more interacting components have been observed and their exact functions approached, thus ensuring the most complicated understanding of this pathway in normal organism development and disorders. In hepatocellular carcinoma (HCC), with a deeply understanding of this pathway, more and more genes which contribute to aberrant activation of Wnt/?-catenin signaling pathway has recently been identified and their exact roles in HCC pursued. In this review, we will focus on a mostly updated understanding of this pathway and its observed role in HCC by emphasizing the gene defects identified to promote tumorigenesis and development.

关键词： interacting     complicated understanding     embryogenesis     activation     organism development    

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Regeneration of hair cells in the mammalian vestibular system

null

《医学前沿（英文）》 2016年 第10卷 第2期   页码 143-151 doi: 10.1007/s11684-016-0451-1

摘要：

Hair cells regenerate throughout the lifetime of non-mammalian vertebrates, allowing these animals to recover from hearing and balance deficits. Such regeneration does not occur efficiently in humans and other mammals. Thus, balance deficits become permanent and is a common sensory disorder all over the world. Since Forge and Warchol discovered the limited spontaneous regeneration of vestibular hair cells after gentamicin-induced damage in mature mammals, significant efforts have been exerted to trace the origin of the limited vestibular regeneration in mammals after hair cell loss. Moreover, recently many strategies have been developed to promote the hair cell regeneration and subsequent functional recovery of the vestibular system, including manipulating the Wnt, Notch and Atoh1. This article provides an overview of the recent advances in hair cell regeneration in mammalian vestibular epithelia. Furthermore, this review highlights the current limitations of hair cell regeneration and provides the possible solutions to regenerate functional hair cells and to partially restore vestibular function.

关键词： utricle     hair cell     regeneration     Atoh1     Notch     Wnt    

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MicroRNA-148b promotes proliferation of hair follicle cells by targeting

Wanbao YANG,Qinqun LI,Bo SU,Mei YU

《农业科学与工程前沿（英文）》 2016年 第3卷 第1期   页码 72-80 doi: 10.15302/J-FASE-2016089

摘要： MicroRNAs (miRNAs), small non-coding RNAs, are involved in many aspects of biological processes. Previous studies have indicated that miRNAs are important for hair follicle development and growth. In our study, we found by qRT-PCR that miR-148b was significantly upregulated in sheep wool follicle bulbs in anagen phase compared with the telogen phase of the hair follicle cycle. Overexpression of miR-148b promoted proliferation of both HHDPC and HHGMC. By using the TOPFlash system we demonstrated that miR-148b could activate Wnt/β-catenin pathway and , , and were consistently upregulated accordingly. Furthermore, transcript factor nuclear factor of activated T cells type 5 ( ) and were predicted to be the target of miR-148b and this was substantiated using a Dual-Luciferase reporter system. Subsequently was further identified as the target of miR-148b using western blotting. These results were considered to indicate that miR-148b could activate the Wnt/β-catenin signal pathway by targeting to promote the proliferation of human hair follicle cells.

关键词： miR-148b     hair follicle     proliferation     NFAT5     Wnt10b    

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Intestinal Epithelial Axin1 Deficiency Protects Against Colitis via Altered Gut Microbiota

Shari Garrett,Yongguo Zhang,Yinglin Xia,Jun Sun,

《工程（英文）》 doi: 10.1016/j.eng.2023.06.007

摘要： Intestinal homeostasis is maintained by specialized host cells and the gut microbiota. Wnt/β-catenin signaling is essential for gastrointestinal development and homeostasis, and its dysregulation has been implicated in inflammation and colorectal cancer. Axin1 negatively regulates activated Wnt/β-catenin signaling, but little is known regarding its role in regulating host–microbial interactions in health and disease. Here, we aim to demonstrate that intestinal Axin1 determines gut homeostasis and host response to inflammation. Axin1 expression was analyzed in human inflammatory bowel disease datasets. To explore the effects and mechanism of intestinal Axin1 in regulating intestinal homeostasis and colitis, we generated new mouse models with Axin1 conditional knockout in intestinal epithelial cell (IEC; Axin1ΔIEC) and Paneth cell (PC; Axin1ΔPC) to compare with control (Axin1LoxP; LoxP: locus of X-over, P1) mice. We found increased Axin1 expression in the colonic epithelium of human inflammatory bowel disease (IBD). Axin1ΔIEC mice exhibited altered goblet cell spatial distribution, PC morphology, reduced lysozyme expression, and enriched Akkermansia muciniphila (A. muciniphila). The absence of intestinal epithelial and PC Axin1 decreased susceptibility to dextran sulfate sodium-induced colitis in vivo. Axin1ΔIEC and Axin1ΔPC mice became more susceptible to dextran sulfate sodium (DSS)-colitis after cohousing with control mice. Treatment with A. muciniphila reduced DSS-colitis severity. Antibiotic treatment did not change the IEC proliferation in the Axin1Loxp mice. However, the intestinal proliferative cells in Axin1ΔIEC mice with antibiotic treatment were reduced compared with those in Axin1ΔIEC mice without treatment. These data suggest non-colitogenic effects driven by the gut microbiome. In conclusion, we found that the loss of intestinal Axin1 protects against colitis, likely driven by epithelial Axin1 and Axin1-associated A. muciniphila. Our study demonstrates a novel role of Axin1 in mediating intestinal homeostasis and the microbiota. Further mechanistic studies using specific Axin1 mutations elucidating how Axin1 modulates the microbiome and host inflammatory response will provide new therapeutic strategies for human IBD.

关键词： Axin1     Bacteria     Microbiome inflammation     Inflammatory bowel disease     Immunity     Microbiome     Paneth cells     Akkermansia muciniphila     Wnt    

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Synthesis of copolymers of 3-acryloyloxymethyl-3′-methyloxetane and 3-(2-(2-(2-Methoxyethylenoxy)ethylenoxy)ethylenoxy)-3′-methyloxetane and their ionic conductivity properties

YE Lin, ZHAO Yumei, FENG Zengguo, BAI Ying, WU Feng

《化学科学与工程前沿（英文）》 2007年 第1卷 第4期   页码 343-348 doi: 10.1007/s11705-007-0062-0

摘要： An oxetane-derived monomer, 3-acryloyloxymethyl-3′-methyloxetane (AMO) was prepared from the reaction of 3-hydromethyl-3-methyloxetane with acryloyl chloride. The cationic ring-opening copolymerization of AMO with another oxetane-derived monomer, 3-(2-(2-(2-methoxyethylenoxy)ethylenoxy)ethylenoxy)-3′-methyloxetane (MEMO) was conducted in CHCl solution using BF3 ·OEt/1, 4-butanediol as a co-initiator. The resulting copolymers were characterized by FTIR, H NMR and Gel Permeation Chromatography (GPC) analyses, and it was found that the enchained ratio of AMO in the copolymers is far lower than its feed ratio. They were crosslinked via the radical polymerization of the vinyl group initiated by BPO after doping with lithium trifluoromethanesulfonimide (LiTFSI) to give rise to tough polymeric electrolyte films. The ionic conductivity was measured at varying content of AMO and different concentration of lithium salt LiTFSI by AC impedance, and a maximum ion conductivity of 1.44×10 S/cm at 30°C or 1.25×10 S/cm at 80°C was attained in the sample PAM 33 at the mole ratio of O : Li = 20. The DSC results indicated that decreases with the increase of the proportion of AMO in the copolymer, well consistent with the ion conductivity trend. The TGA (thermogravimetric analysis) measurement revealed that this kind of copolymer electrolytes is more thermostable than their liquid counterparts.

关键词： 4-butanediol     2-methoxyethylenoxy     consistent     oxetane-derived     copolymer    

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Heterologous expression of signal protein 14-3-3 in and the subsequent immune response in mice

ZHENG Meijuan, SHEN Jilong, LUO Qingli, XU Yuanhong

《医学前沿（英文）》 2008年 第2卷 第1期   页码 95-99 doi: 10.1007/s11684-008-0017-y

摘要： Schistosomiasis japonica, a zoonosis caused by , is endemic to the Philippines and China. Several vaccine candidates have been identified and tested in different animal models, but it is still unclear which will be optimal for testing in the field. Therefore, new antigens and strategies are necessary for vaccine development against schistosomiasis japonica. The Sj14-3-3 gene was amplified and subcloned into the expression vector pPICZ?-B and transformed into X-33 by electroporation. Three transformants were induced with methanol. The cultural supernatant was collected and tested by SDS-PAGE and Western blotting. The protein of rSj14-3-3 was prepared and purified and BALB/c mice were immunized which was followed by a challenging infection. The immuno-protection was then evaluated. The Sj14-3-3 gene was expressed and secreted into the medium and its molecular weight was about 35000 as determined by SDS-PAGE. Western blotting showed that the protein had a high specificity against mouse-anti-Sj14-3-3 monoclonal antibody and rSj14-3-3 had a promising immune reactivity. The results of the immuno-protective experiments revealed that the worm reduction was 26.0%, 32.2%, and 36.8%, respectively. The number of eggs in liver tissue was reduced by 36.8%, 43.2%, and 46.1%, respectively. The recombinant Sj14-3-3 of eukaryotic expression in was successfully harvested. The molecular vaccine of Sj14-3-3 could partially induce resistance to the infection with in BALB/c mice. The recombinant protein Sj14-3-3 has promising immunological potentials for further approach to the diagnosis and development of molecular vaccine.

关键词： development     challenging     rSj14-3-3     resistance     cultural supernatant    

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第四届高性能编译、计算和通信国际会议(HP3C 2020)

会议日期： 2020年03月12日

会议地点： 广东广州

主办单位： HP3C 2020

作为免疫疗法靶点的FOXP3及其辅因子 Review

Yasuhiro Nagai,Lian Lam,Mark I. Greene,Hongtao Zhang

《工程（英文）》 2019年 第5卷 第1期   页码 115-121 doi: 10.1016/j.eng.2019.01.001

摘要：

叉头框蛋白P3（FOXP3）是调节性T细胞（Tregs）的一个主要调节因子，调节性T细胞是能抑制抗原特异性免疫反应的T 细胞亚群，在增强宿主耐受性和维持免疫平衡方面发挥着重要作用。众所周知，FOXP3 与多种蛋白质形成复合物，并能通过乙酰化、磷酸化、泛素化和甲基化等各种翻译后修饰（PTM）进行调节。因此，翻译后修饰可改变FOXP3 的稳定性及其调节基因表达的能力，并最终影响调节性T细胞活性。虽然FOXP3 自身并非理想的药物靶点，但脱乙酰酶、乙酰转移酶、激酶和其他可调节FOXP3 的翻译后修饰的酶均为调控FOXP3 和调节性T细胞活性的潜在靶点。但FOXP3 并非这些酶的唯一底物；因此，当使用相关抑制剂时，必须考虑是否存在有害的“FOXP3脱靶”副作用。

关键词： 调节性T细胞     叉头框蛋白P3（FOXP3）     翻译后修饰     自体免疫     癌症    

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Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and

《医学前沿（英文）》 doi: 10.1007/s11684-023-1003-0

摘要： Lipin proteins including Lipin 1–3 act as transcriptional co-activators and phosphatidic acid phosphohydrolase enzymes, which play crucial roles in lipid metabolism. However, little is known about the function of Lipin3 in triglyceride (TG) metabolism. Here, we identified a novel mutation (NM_001301860: p.1835A>T/p.D612V) of Lipin3 in a large family with hypertriglyceridemia (HTG) and obesity through whole-exome sequencing and Sanger sequencing. Functional studies revealed that the novel variant altered the half-life and stability of the Lipin3 protein. Hence, we generated Lipin3 heterozygous knockout (Lipin3-heKO) mice and cultured primary hepatocytes to explore the pathophysiological roles of Lipin3 in TG metabolism. We found that Lipin3-heKO mice exhibited obvious obesity, HTG, and non-alcoholic fatty liver disorder. Mechanistic study demonstrated that the haploinsufficiency of Lipin3 in primary hepatocytes may induce the overexpression and abnormal distribution of Lipin1 in cytosol and nucleoplasm. The increased expression of Lipin1 in cytosol may contribute to TG anabolism, and the decreased Lipin1 in nucleoplasm can reduce PGC1α, further leading to mitochondrial dysfunction and reduced TG catabolism. Our study suggested that Lipin3 was a novel disease-causing gene inducing obesity and HTG. We also established a relationship between Lipin3 and mitochondrial dysfunction.

关键词： Lipin3     Lipin1     hypertriglyceridemia     obesity     mitochondrial dysfunction    

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关于3D打印技术在医学模具以及再生组织和器官方面的应用综述

Kan Wang, Chia-Che Ho, Chuck Zhang, Ben Wang

《工程（英文）》 2017年 第3卷 第5期   页码 653-662 doi: 10.1016/J.ENG.2017.05.013

摘要： 随着三维（3D）打印和3D 生物打印技术的快速发展，许多研究人员已经开始使用增材制造技术来生产具有多种功能的医学模具。本文综述了3D 打印和3D 生物打印技术在制作功能性医学模具和生物结构方面的应用。特别讨论了3D 打印功能性医学模具（即组织模拟医学模具、放射性医学模具和生理医学模具）及被用于再生组织和器官的3D 生物打印模具的制备（即混合模式支架材料、可转换支架和集成传感器）工艺、发展现状以及未来发展趋势

关键词： 3D打印     3D生物打印     医学模具     再生组织/器官     支架    

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标题 作者 时间 类型 操作

ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/-catenin signaling

期刊论文

Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling

null

期刊论文

Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea

null

期刊论文

Unidirectional and stage-dependent roles of Notch1 in Wnt-responsive Lgr5

Hui Jiang, Shan Zeng, Wenli Ni, Yan Chen, Wenyan Li

期刊论文

Wnt/β-catenin signaling pathway and its role in hepatocellular carcinoma

ZHANG Xufeng, YU Liang, LU Yi

期刊论文

Regeneration of hair cells in the mammalian vestibular system

null

期刊论文

MicroRNA-148b promotes proliferation of hair follicle cells by targeting

Wanbao YANG,Qinqun LI,Bo SU,Mei YU

期刊论文

Intestinal Epithelial Axin1 Deficiency Protects Against Colitis via Altered Gut Microbiota

Shari Garrett,Yongguo Zhang,Yinglin Xia,Jun Sun,

期刊论文

虞晓含：中医话健康，食补改善免疫力（2020年3月1日）

2022年04月18日

会议视频

Synthesis of copolymers of 3-acryloyloxymethyl-3′-methyloxetane and 3-(2-(2-(2-Methoxyethylenoxy)ethylenoxy)ethylenoxy)-3′-methyloxetane and their ionic conductivity properties

YE Lin, ZHAO Yumei, FENG Zengguo, BAI Ying, WU Feng

期刊论文

Heterologous expression of signal protein 14-3-3 in and the subsequent immune response in mice

ZHENG Meijuan, SHEN Jilong, LUO Qingli, XU Yuanhong

期刊论文

第四届高性能编译、计算和通信国际会议(HP3C 2020)

2020年03月12日

会议信息

作为免疫疗法靶点的FOXP3及其辅因子

Yasuhiro Nagai,Lian Lam,Mark I. Greene,Hongtao Zhang

期刊论文

Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and

期刊论文

关于3D打印技术在医学模具以及再生组织和器官方面的应用综述

Kan Wang, Chia-Che Ho, Chuck Zhang, Ben Wang

期刊论文