摘要：
通过网络药理学及动物试验探讨抗纤灵方治疗肝纤维化的作用机制。采用TCMSP、PubChem等数据库筛选出抗纤灵方的有效成分和潜在的相关靶点；利用GeneCards数据库检索肝纤维化的相关靶点；根据药物和疾病匹配的共同靶点，利用STRING数据库进行蛋白质互作分析；构建蛋白质网络，拓扑分析关键靶点；利用Metascape平台对共有靶点进行GO（Gene Ontology）及KEGG（Kyoto Encyclopedia of Genes and Genomes）富集分析以探讨其可能的机制。建立四氯化碳诱导小鼠肝纤维化模型，利用HE染色及Masson染色分析肝组织的病理变化及纤维化程度；试剂盒检测小鼠血清中ALT、AST的表达水平；ELISA检测抗纤灵方对炎性因子TNF、IL-6、IL-1的表达水平。肝组织匀浆检测抗纤灵方对纤维化标志物的影响。抗纤灵方抗肝纤维化的核心活性成分为橘皮素、儿茶素、表小檗碱、黄连碱等。核心靶点有TNF、IL-6、AKT1、TP53等，核心通路包括癌症通路、TNF、流体剪切力与动脉粥样硬化、IL-17、糖尿病并发症中的AGE-RAGE信号通路等。动物试验表明，抗纤灵方可以减少小鼠肝脏炎症细胞浸润及胶原产生，降低炎性因子TNF、IL-6、IL-1水平，抑制肝星状细胞活化指标-SMA等的表达。抗纤灵方可能通过降低炎性因子的水平，抑制肝星状细胞活化从而发挥抗肝纤维化的作用。
期刊：
Current Issues in Molecular Biology,2023年45(10):8215-8226 ISSN：1467-3045
通讯作者：
Hu, X;Xiang, SL
作者机构：
[Zhang, Hongning; Wang, Jiawei; Zhang, Jian; Chen, Wen; He, Meiqi; Hu, Xiang; Wu, Zhen; Hu, X; Huang, Shulan] Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Changsha 410081, Peoples R China.;[Xiang, Shuanglin] Hunan Normal Univ, Coll Life Sci, Engn Res Ctr Antibodies Expt Anim Hunan Prov, Changsha 410081, Peoples R China.
通讯机构：
[Xiang, SL ; Hu, X ] H;Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Changsha 410081, Peoples R China.;Hunan Normal Univ, Coll Life Sci, Engn Res Ctr Antibodies Expt Anim Hunan Prov, Changsha 410081, Peoples R China.
关键词：
Tnfaip1;zebrafish embryos;cDNA library;yeast two-hybrid system;interacting protein
摘要：
TNFAIP1 regulates cellular biological functions, including DNA replication, DNA repair, and cell cycle, by binding to target proteins. Identification of Tnfaip1-interacting proteins contributes to the understanding of the molecular regulatory mechanisms of their biological functions. In this study, 48 hpf, 72 hpf, and 96 hpf wild-type zebrafish embryo mRNAs were used to construct yeast cDNA library. The library titer was 1.12 × 107 CFU/mL, the recombination rate was 100%, and the average length of the inserted fragments was greater than 1000 bp. A total of 43 potential interacting proteins of Tnfaip1 were identified using zebrafish Tnfaip1 as a bait protein. Utilizing GO functional annotation and KEGG signaling pathway analysis, we found that these interacting proteins are mainly involved in translation, protein catabolic process, ribosome assembly, cytoskeleton formation, amino acid metabolism, and PPAR signaling pathway. Further yeast spotting analyses identified four interacting proteins of Tnfaip1, namely, Ubxn7, Tubb4b, Rpl10, and Ybx1. The Tnfaip1-interacting proteins, screened from zebrafish embryo cDNA in this study, increased our understanding of the network of Tnfaip1-interacting proteins during the earliest embryo development and provided a molecular foundation for the future exploration of tnfaip1’s biological functions.
作者机构：
[Zhang, Hongning; Zhang, Jian; Chen, Wen; Hu, Xiang; Yuan, Changyue; Hu, X; Huang, Shulan; Su, Na] Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Changsha 410081, Peoples R China.;[Chen, Wen] Hunan Univ Chinese Med, Med Sch, Key Lab Vasc Biol & Translat Med, Changsha 410208, Peoples R China.;[Xiang, Shuanglin; Su, Na] Hunan Normal Univ, Coll Life Sci, Engn Res Ctr Antibodies Expt Anim Hunan Prov, Changsha 410081, Peoples R China.
通讯机构：
[Xiang, SL ; Hu, X ] H;Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Changsha 410081, Peoples R China.;Hunan Normal Univ, Coll Life Sci, Engn Res Ctr Antibodies Expt Anim Hunan Prov, Changsha 410081, Peoples R China.
摘要：
TNF α-induced protein 1 (TNFAIP1) was first identified in human umbilical vein endothelial cells and can be induced by tumor necrosis factor α (TNFα). Early studies have found that TNFAIP1 is involved in the development of many tumors and is closely associated with the neurological disorder Alzheimer’s disease. However, little is known about the expression pattern of TNFAIP1 under physiological conditions and its function during embryonic development. In this study, we used zebrafish as a model to illustrate the early developmental expression pattern of tnfaip1 and its role in early development. First, we examined the expression pattern of tnfaip1 during early zebrafish development using quantitative real-time PCR and whole mount in situ hybridization and found that tnfaip1 was highly expressed in early embryonic development and, subsequently, expression became localized to anterior embryonic structures. To investigate the function of tnfaip1 during early development, we constructed a model of a stably inherited tnfaip1 mutant using the CRISPR/Cas9 system. Tnfaip1 mutant embryos showed significant developmental delays as well as microcephaly and microphthalmia. At the same time, we found decreased expression of the neuronal marker genes tuba1b, neurod1, and ccnd1 in tnfaip1 mutants. Analysis of transcriptome sequencing data revealed altered expression of the embryonic development related genes dhx40, hspa13, tnfrsf19, nppa, lrp2b, hspb9, clul1, zbtb47a, cryba1a, and adgrg4a in the tnfaip1 mutants. These findings suggest an important role for tnfaip1 in the early development of zebrafish.
期刊：
Cell Death & Disease,2023年14(4):235 ISSN：2041-4889
通讯作者：
Cheng, Q.;Liu, G.
作者机构：
[Cheng, Yuan; Liu, Guodong; Zhang, Hao; Luo, Hong; Zhao, Guanjian; Xie, Zongyi; Tao, Yihao] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing, Peoples R China.;[Mao, Jinning] Chongqing Med Univ, Affiliated Hosp 2, Hlth management Ctr, Chongqing, Peoples R China.;[Cao, Hui] Brain Hosp Hunan Prov, Peoples Hosp Hunan Prov 2, Changsha, Peoples R China.;[Cao, Hui] Hunan Univ Chinese Med, Sch Clin Med, Changsha, Peoples R China.;[Zhang, Zhiwen] Fudan Univ, Sch Pharm, Shanghai, Peoples R China.
通讯机构：
[Cheng, Quan; Liu, Guodong] D;Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China<&wdkj&>Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
摘要：
Exosomes, the cell-derived small extracellular vehicles, play a vital role in intracellular communication by reciprocally transporting DNA, RNA, bioactive protein, chains of glucose, and metabolites. With great potential to be developed as targeted drug carriers, cancer vaccines and noninvasive biomarkers for diagnosis, treatment response evaluation, prognosis prediction, exosomes show extensive advantages of relatively high drug loading capacity, adjustable therapeutic agents release, enhanced permeation and retention effect, striking biodegradability, excellent biocompatibility, low toxicity, etc. With the rapid progression of basic exosome research, exosome-based therapeutics are gaining increasing attention in recent years. Glioma, the standard primary central nervous system (CNS) tumor, is still up against significant challenges as current traditional therapies of surgery resection combined with radiotherapy and chemotherapy and numerous efforts into new drugs showed little clinical curative effect. The emerging immunotherapy strategy presents convincing results in many tumors and is driving researchers to exert its potential in glioma. As the crucial component of the glioma microenvironment, tumor-associated macrophages (TAMs) significantly contribute to the immunosuppressive microenvironment and strongly influence glioma progression via various signaling molecules, simultaneously providing new insight into therapeutic strategies. Exosomes would substantially assist the TAMs-centered treatment as drug delivery vehicles and liquid biopsy biomarkers. Here we review the current potential exosome-mediated immunotherapeutics targeting TAMs in glioma and conclude the recent investigation on the fundamental mechanisms of diversiform molecular signaling events by TAMs that promote glioma progression.
摘要：
A TGF‐β signaling‐related lncRNA signature has been established in glioma, which can be used for prognostic judgment, immune infiltration status speculation, and immunotherapy response prediction. Furthermore, in vitro experiments confirmed that silencing of TGF‐β signaling‐related lncRNA could inhibit the proliferation of glioma cells. This study provides candidate biomarkers with clinical application value for glioma. Abstract Aims The dysregulation of TGF‐β signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF‐β signaling in glioma is currently unclear. Methods Data on glioma's RNA‐seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. “ELMER v.2” was used to reconstruct TF‐methylation‐gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. In vitro and in vivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA. Results In glioma, a TGF‐β signaling‐related 15‐lncRNA signature was constructed, including AC010173.1, HOXA‐AS2, AC074286.1, AL592424.1, DRAIC, HOXC13‐AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC‐AS1, AGAP2‐AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP‐1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2‐AS1 knockdown in in vitro and in vivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF‐κB and ERK 1/2 in the TGF‐β signaling pathway. Conclusions A prognostic lncRNA signature of TGF‐β signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2‐AS1 plays an important role in glioma progression.
通讯机构：
[Zhixiong Liu; Quan Cheng] D;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
摘要：
Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies’ clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.
期刊：
FRONTIERS IN IMMUNOLOGY,2022年13:1040289 ISSN：1664-3224
通讯作者：
Cheng, Q.;Zhang, H.
作者机构：
[Li, He] The Animal Laboratory Center, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China;[Chen, Shi; Zhou, Ke] School of Medicine, Hunan Normal University, Changsha, China;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Hunan, Changsha, China;Brain Hospital of Hunan Province, The Second People’s Hospital of Hunan Province, Changsha, China
通讯机构：
[Cheng, Q.; Zhang, H.] D;Department of Neurosurgery, China
