期刊：
Journal of Autoimmunity,2022年133:102919 ISSN：0896-8411
通讯作者：
Liuting Zeng
作者机构：
[Zeng, Liuting; Chen, Hua] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Natl Clin Res Ctr Dermatol & Immunol Dis, Dept Rheumatol, Beijing, Peoples R China.;[Zhang, Tianqing; Zhu, Xiaofei; Yang, Kailin; Ge, Jinwen] Hunan Univ Chinese Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Peoples R China.;[Ge, Jinwen] Hunan Acad Chinese Med, Changsha, Peoples R China.;[Hao, Wensa] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing, Peoples R China.
通讯机构：
[Liuting Zeng] D;Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Beijing, China
摘要：
Autoimmunity refers to the phenomenon that the body's immune system produces antibodies or sensitized lymphocytes to its own tissues to cause an immune response. Immune disorders caused by autoimmunity can mediate autoimmune diseases. Autoimmune diseases have complicated pathogenesis due to the many types of cells involved, and the mechanism is still unclear. The emergence of single-cell research technology can solve the problem that ordinary transcriptome technology cannot be accurate to cell type. It provides unbiased results through independent analysis of cells in tissues and provides more mRNA information for identifying cell sub-populations, which provides a novel approach to study disruption of immune tolerance and disturbance of pro-inflammatory pathways on a cellular basis. It may fundamentally change the understanding of molecular pathways in the pathogenesis of autoimmune diseases and develop targeted drugs. Single-cell transcriptome sequencing (scRNA-seq) has been widely applied in autoimmune diseases, which provides a powerful tool for demonstrating the cellular heterogeneity of tissues involved in various immune inflammations, identifying pathogenic cell populations, and revealing the mechanism of disease occurrence and development. This review describes the principles of scRNA-seq, introduces common sequencing platforms and practical procedures, and focuses on the progress of scRNA-seq in 41 autoimmune diseases, which include 9 systemic autoimmune diseases and autoinflammatory diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.) and 32 organ-specific autoimmune diseases (5 Skin diseases, 3 Nervous system diseases, 4 Eye diseases, 2 Respiratory system diseases, 2 Circulatory system diseases, 6 Liver, Gallbladder and Pancreas diseases, 2 Gastrointestinal system diseases, 3 Muscle, Bones and joint diseases, 3 Urinary system diseases, 2 Reproductive system diseases). This review also prospects the molecular mechanism targets of autoimmune diseases from the multi-molecular level and multi-dimensional analysis combined with single-cell multi-omics sequencing technology (such as scRNA-seq, Single cell ATAC-seq and single cell immune group library sequencing), which provides a reference for further exploring the pathogenesis and marker screening of autoimmune diseases and autoimmune inflammatory diseases in the future.
摘要：
目的观察脑泰方对大鼠脑出血后脑组织铁沉积致神经细胞过氧化损伤的影响,探讨其作用机制。方法采用自体血注射法构建SD大鼠脑出血模型,随机分为模型组、脑泰方组、阳性对照组、假手术组,各组均于给药7、14、28 d取材;HE染色观察脑组织病理变化,采用Zea Longa 5级评分法进行神经功能缺失评分,免疫组化检测病灶脑组织铁沉积量、丙二醛(MDA)、谷胱甘肽(GSH)含量,免疫荧光技术检测转铁蛋白(Tf)、转铁蛋白受体(TfR)、谷胱甘肽过氧化物酶4(GPX-4)的表达。结果与假手术组同一时点比较,模型组大鼠脑组织TfR和Tf表达上调,GPX-4表达下调,GSH含量下降,铁沉积量和MDA含量升高,神经功能缺失评分升高,差异均有统计学意义(P<0.01,P<0.05);MDA含量与铁含量呈正相关,GSH含量及GPX-4水平与铁含量呈负相关,差异均有统计学意义(P<0.05);与模型组比较,脑泰方组和阳性对照组大鼠脑组织TfR、Tf表达下调,GPX-4表达上调,GSH含量升高,铁沉积量、MDA含量降低,神经功能缺失评分降低,差异均有统计学意义(P<0.01,P<0.05);与阳性对照组比较,脑泰方组对大鼠脑组织MDA、GSH含量调节作用更强,差异有统计学意义(P<0.05)。结论脑泰方可抑制模型大鼠脑组织铁输入蛋白的表达,减轻神经细胞铁超载,增强细胞抗氧化能力而发挥神经保护作用。
摘要：
Objective: Our previous research showed that Naotaifang (a compound traditional Chinese herbal medicine) extract (NTE) has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia. In this study, we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4 (GPX4) and iron metabolism. Methods: We established an acute brain injury model of middle cerebral artery occlusion (MCAO) in rats, in which we could observe the accumulation of iron in neurons, as detected by Perl's staining. Using assay kits, we measured expression levels of ferroptosis biomarkers, such as iron, glutathione (GSH), reactive oxygen species (ROS) and malonaldehyde (MDA); further the expression levels of transferrin receptor 1 (TFR1), divalent metal transporter 1 (DMT1), solute carrier family 7 member 11 (SLC7A11) and GPX4 were determined using immunohistochemical analysis, real-time quantitative polymerase chain reaction and Western blot assays. Results: We found that treatment with NTE reduced the expression levels of TFR1 and DMT1, reduced ROS, MDA and iron accumulation and reduced neurobehavioral scores, relative to untreated MCAO rats. Treatment with NTE increased the expression levels of SLC7A11, GPX4 and GSH, and the number of Nissl bodies in the MCAO rats. Conclusion: Taken together, our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/ DMT1 and SCL7A11/GPX4 pathways. (C) 2020 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.
期刊：
International Journal of Molecular Sciences,2020年21(1)
通讯作者：
Mei, Zhigang
作者机构：
[Du, Lipeng; Liu, Xiaolu; Mei, Zhigang; Feng, Zhitao; Huang, Yaguang] China Three Gorges Univ, Grade Pharmacol Lab Chinese Med 3, State Adm Tradit Chinese Med, Med Coll, Yichang 443002, Peoples R China.;[Deng, Yihui; Ge, Jinwen; Mei, Zhigang] Hunan Univ Chinese Med, Key Lab Hunan Prov Integrated Tradit Chinese & We, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Mei, Zhigang] C;[Mei, Zhigang] H;China Three Gorges Univ, Grade Pharmacol Lab Chinese Med 3, State Adm Tradit Chinese Med, Med Coll, Yichang 443002, Peoples R China.;Hunan Univ Chinese Med, Key Lab Hunan Prov Integrated Tradit Chinese & We, Changsha 410208, Hunan, Peoples R China.
摘要：
Cerebral ischemia injury, the leading cause of morbidity and mortality worldwide, initiates sequential molecular and cellular pathologies that underlie ischemic encephalopathy (IE), such as ischemic stroke, Alzheimer disease (AD), Parkinson's disease (PD), epilepsy, etc. Targeted therapeutic treatments are urgently needed to tackle the pathological processes implicated in these neurological diseases. Recently, accumulating studies demonstrate that microRNA-124 (miR-124), the most abundant miRNA in brain tissue, is aberrant in peripheral blood and brain vascular endothelial cells following cerebral ischemia. Importantly, miR-124 regulates a variety of pathophysiological processes that are involved in the pathogenesis of age-related IE. However, the role of miR-124 has not been systematically illustrated. Paradoxically, miR-124 exerts beneficial effects in the age-related IE via regulating autophagy, neuroinflammation, oxidative stress, neuronal excitability, neurodifferentiation, A beta deposition, and hyperphosphorylation of tau protein, while it may play a dual role via regulating apoptosis and exerts detrimental effects on synaptic plasticity and axonal growth. In the present review, we thus focus on the paradoxical roles of miR-124 in age-related IE, as well as the underlying mechanisms. A great understanding of the effects of miR-124 on the hypoxic-ischemic brain will open new avenues for therapeutic approaches to protect against cerebral ischemia injury.
作者机构：
[资冬; 张君宇; 王婧; 任永镇; 朱伟] Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, 410208, China;Hunan Key Lab of Powder and Innovative Drugs, Slate Key Lab of Ministry Training Bases, Changsha, 410208, China;[葛金文; 刘洋] Key Lab of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardiocerebral Diseases, Hunan University of Chinese Medicine, Changsha, 410208, China;[雷昌; 张秀丽] Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, 410208, China, Hunan Key Lab of Powder and Innovative Drugs, Slate Key Lab of Ministry Training Bases, Changsha, 410208, China
期刊：
Oxidative Medicine and Cellular Longevity,2020年2020 ISSN：1942-0900
通讯作者：
Ge, Jinwen;Zeng, Liuting
作者机构：
[Yang, Kailin; Ge, Anqi] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha, Hunan, Peoples R China.;[Zhu, Xiaofei; Yang, Kailin; Shi, Yongmei; Ge, Jinwen; Liu, Wenlong] Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China.;[Yang, Kailin] Capital Med Univ, Beijing, Peoples R China.;[Zeng, Liuting] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Rheumatol & Clin Immunol, Beijing, Peoples R China.
通讯机构：
[Ge, Jinwen] H;[Zeng, Liuting] C;Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Rheumatol & Clin Immunol, Beijing, Peoples R China.
摘要：
Background.Hedysarum multijugum Maxim.-Chuanxiong rhizomacompound (HCC) is a common herbal formula modified from Buyang Huanwu decoction. Clinical trials have demonstrated its therapeutic potential for ischemic stroke (IS). However, the mechanism of HCC remains unclear.Methods. The HCC's components were collected from the TCMSP database and TCM@Taiwan database. After that, the HCC's compound targets were predicted by PharmMapper. The IS-related genes were obtained from GeneCards, and OMIM and the protein-protein interaction (PPI) data of HCC's targets and IS genes were obtained from the String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis and the Cytoscape 3.7.2 was utilized to construct and analyze the networks. Finally, a series of animal experiments were carried out to validate the prediction results of network pharmacology. The expressions of GRP78, p-PERK, and CHOP proteins and mRNAs in different time periods after HCC intervention were detected by Western blot, immunohistochemistry, and RT-qPCR.Results. A total of 440 potential targets and 388 IS genes were obtained. The results of HCC-IS PPI network analysis showed that HCC may regulate IS-related targets (such as ALB, AKT1, MMP9, IGF1, and CASP3), biological processes (such as endoplasmic reticulum stress, inflammation modules, hypoxia modules, regulation of neuronal apoptosis and proliferation, and angiogenesis), and signaling pathways (such as PI3K-Akt, FoxO, TNF, HIF-1, and Rap1 signaling). The animal experiments showed that HCC can improve the neurobehavioral scores and protect the neurons of IS rats (P<0.05). HCC inhibited the expression of p-PERK in the PERK pathway from 12 h after surgery, significantly promoted the expression of GRP78 protein, and inhibited the expression of CHOP protein after surgery, especially at 24 h after surgery (P<0.05). The results of RT-qPCR showed that HCC can significantly reduce the expression of CHOP mRNA in the neurons in the CA1 region of the hippocampus 72 h after MCAO (P<0.05).Conclusion. HCC may achieve a role in the treatment of IS by intervening in a series of targets, signaling pathways, and biological processes such as inflammation, oxidative stress, endoplasmic reticulum stress, and angiogenesis.
摘要：
Ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. As the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. In response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the antiinflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. It has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. In addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified.
期刊：
Journal of Cellular and Molecular Medicine,2020年24(23):13876-13898 ISSN：1582-1838
通讯作者：
Zeng, Liuting;Ge, Jinwen;Huang, Zhengde
作者机构：
[Yang, Kailin; Ge, Anqi] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha, Peoples R China.;[Tong, Qiaozhen; Pan, Xiaoping; Yang, Kailin; Ge, Anqi; Ge, Jinwen; Huang, Zhengde; Zeng, LT; Ge, JN; Huang, ZD] Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China.;[Yang, Kailin] Capital Med Univ, Beijing, Peoples R China.;[Zeng, Liuting] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Rheumatol & Clin Immunol, Beijing, Peoples R China.;[Bao, Tingting] China Acad Chinese Med Sci, Guanganmen Hosp, Beijing, Peoples R China.
通讯机构：
[Zeng, LT; Ge, JN; Huang, ZD] H;Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China.
摘要：
This research utilized the systematic biological and proteomics strategies to explore the regulatory mechanism of Danshen Yin Modified (DSYM) on atherosclerosis (AS) biological network. The traditional Chinese medicine database and HPLC was used to find the active compounds of DSYM, Pharmmapper database was used to predict potential targets, and OMIM database and GeneCards database were used to collect AS targets. String database was utilized to obtain the other protein of proteomics proteins and the protein-protein interaction (PPI) data of DSYM targets, AS genes, proteomics proteins and other proteins. The Cytoscape 3.7.1 software was utilized to construct and analyse the network. The DAVID database is used to discover the biological processes and signalling pathways that these proteins aggregate. Finally, animal experiments and proteomics analysis were used to further verify the prediction results. The results showed that 140 active compounds, 405 DSYM targets and 590 AS genes were obtained, and 51 differentially expressed proteins were identified in the DSYM-treated ApoE-/- mouse AS model. A total of 4 major networks and a number of their derivative networks were constructed and analysed. The prediction results showed that DSYM can regulate AS-related biological processes and signalling pathways. Animal experiments have also shown that DSYM has a therapeutic effect on ApoE-/-mouse AS model (P < .05). Therefore, this study proposed a new method based on systems biology, proteomics, and experimental pharmacology, and analysed the pharmacological mechanism of DSYM. DSYM may achieve therapeutic effects by regulating AS-related signalling pathways and biological processes found in this research.
