Ziyi Chen

Qingdao University

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Bingyin Shi

Xi'an Jiaotong University

Mingqian He

First Affiliated Hospital of Xi'an Jiaotong University

Meng Zhang

Nanjing University of Aeronautics and Astronautics

Xi Ding

Sun Yat-sen University

Lu Chen

Jinan University

Xuehao Wang

Jiangsu Province Hospital

Jing Zhu

Xinjiang Academy of Agricultural Sciences

Doudou Wang

Beijing Normal University

Shiqian Hu

First Affiliated Hospital of Xi'an Jiaotong University

Hong Fan

Second Affiliated Hospital of Xi'an Jiaotong University

Cooperative Institutions

Xi'an Jiaotong University

Chinese Academy of Medical Sciences & Peking Union Medical College

First Affiliated Hospital of Xi'an Jiaotong University

Peking University

Chinese Academy of Sciences

Nanjing Medical University

Shanghai Jiao Tong University

Sun Yat-sen University

Capital Medical University

Central South University

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Defective mitophagy in aged macrophages promotes mitochondrial DNA cytosolic leakage to activate STING signaling during liver sterile inflammation

Aging Cell (2022)

Weizhe Zhong Zhuqing Rao Jian Xu Yu Sun Haoran Hu

Abstract Macrophage‐stimulator of interferon genes (STING) signaling mediated sterile inflammation has been implicated in various age‐related diseases. However, whether and how macrophage mitochondrial DNA (mtDNA) regulates STING signaling in aged macrophages remains largely unknown. We found that hypoxia‐reoxygenation (HR) induced STING activation in macrophages by triggering the release of macrophage mtDNA into the cytosol. Aging promoted the cytosolic leakage of macrophage mtDNA and enhanced STING activation, which was abrogated upon mtDNA depletion or cyclic GMP‐AMP Synthase (cGAS) inhibition. Aged macrophages exhibited increased mitochondrial injury with impaired mitophagy. Mechanistically, a decline in the PTEN‐induced kinase 1 (PINK1)/Parkin‐mediated polyubiquitination of mitochondria was observed in aged macrophages. Pink1 overexpression reversed the inhibition of mitochondrial ubiquitination but failed to promote mitolysosome formation in the aged macrophages. Meanwhile, aging impaired lysosomal biogenesis and function in macrophages by modulating the mTOR/transcription factor EB (TFEB) signaling pathway, which could be reversed by Torin‐1 treatment. Consequently, Pink1 overexpression in combination with Torin‐1 treatment restored mitophagic flux and inhibited mtDNA/cGAS/STING activation in aged macrophages. Moreover, besides HR‐induced metabolic stress, other types of oxidative and hepatotoxic stresses inhibited mitophagy and promoted the cytosolic release of mtDNA to activate STING signaling in aged macrophages. STING deficiency protected aged mice against diverse types of sterile inflammatory liver injuries. Our findings suggest that aging impairs mitophagic flux to facilitate the leakage of macrophage mtDNA into the cytosol and promotes STING activation, and thereby provides a novel potential therapeutic target for sterile inflammatory liver injury in aged patients.

PINK1

Mitochondrial ROS

10.1111/acel.13622

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Citations (84)

Target-directed enzyme-free dual-amplification DNA circuit for rapid signal amplification

Journal of Materials Chemistry B (2020)

Chao Xing Ziyi Chen Cheng Zhang Jun Wang Chunhua Lü

Dynamic DNA circuits have shown promising potential for amplified biosensing and bioengineering applications at the molecular level. Here, an enzyme-free, single-step and rapid signal amplification DNA circuit was developed by integrating target-directed entropy-driven catalysis (EDC) and hybridization chain reaction (HCR) for analysis of nucleic acids and small molecules. The target catalyzes the self-assembly of the EDC premade substrate complex and fuel strands to release the hidden amplicon trigger (T), which was encoded with trigger sequences for the downstream HCR circuit. The released T could motivate the successive cross-opening of HCR hairpins yielding long DNA nanowires and generated tremendously amplified fluorescence signals. Notably, this EDC-HCR circuit was driven by entropy without the requirement of any enzymes, thus greatly reducing the cost. The design of the hidden amplicon trigger (T) avoided the production of waste by-products and improved the reaction rate. Furthermore, as a modular circuit, we also demonstrated that our EDC-HCR cascade sensing system could be used as a versatile sensing platform for the highly sensitive and selective detection of other analysts, e.g. ATP in serum samples, through simply programming the reorganization sequences of the initiator. Therefore, the flexible and versatile EDC-HCR platform holds great potential in the fields of clinical diagnosis and biochemical analysis.

SIGNAL (programming language)

Multiple displacement amplification

10.1039/d0tb02114h

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Citations (22)

Expression patterns of eight RNA-modified regulators correlating with immune infiltrates during the progression of osteoarthritis

Frontiers in Immunology (2023)

Ziyi Chen Wenjuan Wang Yinghui Hua

RNA modifications in eukaryotic cells have emerged as an exciting but under-explored area in recent years and are considered to be associated with many human diseases. While several studies have been published relating to m6A in osteoarthritis (OA), we only have limited knowledge of other kinds of RNA modifications. Our study investigated eight RNA modifiers' specific roles in OA including A-to-I, APA, m5C, m6A, m7G, mcm5s2U, Nm and Ψ together with their relationship with immune infiltration.

10.3389/fimmu.2023.1019445

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<p>Star Circular RNAs In Human Cancer: Progress And Perspectives</p>

OncoTargets and Therapy (2019)

Ye Cheng Hanzhi Sun Hanjin Wang Wei Jiang Weiwei Tang

Circular RNAs (circRNAs) are a recently discovered subclass of non-coding RNAs (ncRNAs) characterized by a covalently closed loop structure created by reverse splicing. Because they do not have a 5' cap structure and a 3' poly A tail, circRNAs have higher stability, abundance and evolutionary conservation than linear RNA between species. These features produce various potential biological functions of circRNAs, such as miRNA sponges, RNA-binding proteins that form RNA protein complexes. In recent years, more and more studies have shown that circRNAs play a vital role in the occurrence and development of human diseases. At the same time, their enormous potential as a biomarker and therapeutic target is also evolving. The purpose of this review is to summarize existing cancer-associated circRNAs and to try to find circRNAs that are abnormally expressed in many cancers. Therefore, we reviewed previous circRNAs studies related to cancer and selected them by statistics. The eight circRNAs that have the highest frequency in different cancers or involve key pathways are called star circRNAs. Here, we review the classification, features, and functions of emerging star circRNAs, with particular attention to the role of circRNAs in various cancers.

Star (game theory)

10.2147/ott.s215390

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Citations (13)

Disinfection Effects and Operating Conditions of Tea Polyphenols Combined with Ozone

Ozone Science and Engineering (2020)

Cuimin Feng Ting Wang Changzheng Wang Xi Chen Ziyu Guo

Ozone disinfection is an efficient method, but it has no persistent disinfection effect, which is the main factor restricting its development. However, tea polyphenols are a renewable green resource and have continuous disinfection effect in drinking water treatment. Thus, it is beneficial to make tea polyphenols an auxiliary disinfectant to ozone disinfection, explore the combined disinfection effect of ozone and tea polyphenols, and optimize its operating conditions. The optimal disinfection effect of the combined disinfectant was determined by using a response surface analysis (RSA). This method of experimental design with three factors and three levels was used to establish a regression model for analysis. The results showed that the dosage of tea polyphenols was the most significant influencing factor; combined with ozone, the half-life of tea polyphenols was extended from 15 h to 77 h, which could achieve continuous control of network microorganisms. The optimal operating condition of the combined disinfectant was an ozone dosage of 2.5 mg/L, ozone contact time of 25 min, and tea polyphenol dosage of 20 mg/L. The advantages of tea polyphenols and ozone can be well exerted under these conditions, which will ensure the safety of effluent from microbes.

Disinfectant

Central composite design

10.1080/01919512.2020.1746632

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Citations (15)

Scorpion Toxins from Buthus martensii Karsch All Possess a Predicted alpha-Tight-Turn

Cell Biochemistry and Biophysics (2002)

Richard Hahin Ziyi Chen Danhui Wang Giridher Reddy Long Mao

10.1385/cbb:37:3:169

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Citations (1)

A novel CD4+ CTL subtype characterized by chemotaxis and inflammation is involved in the pathogenesis of Graves’ orbitopathy

Cellular and Molecular Immunology (2021)

Yue Wang Ziyi Chen Tingjie Wang Hui Guo Yufeng Liu

Abstract Graves’ orbitopathy (GO), the most severe manifestation of Graves’ hyperthyroidism (GH), is an autoimmune-mediated inflammatory disorder, and treatments often exhibit a low efficacy. CD4+ T cells have been reported to play vital roles in GO progression. To explore the pathogenic CD4+ T cell types that drive GO progression, we applied single-cell RNA sequencing (scRNA-Seq), T cell receptor sequencing (TCR-Seq), flow cytometry, immunofluorescence and mixed lymphocyte reaction (MLR) assays to evaluate CD4+ T cells from GO and GH patients. scRNA-Seq revealed the novel GO-specific cell type CD4+ cytotoxic T lymphocytes (CTLs), which are characterized by chemotactic and inflammatory features. The clonal expansion of this CD4+ CTL population, as demonstrated by TCR-Seq, along with their strong cytotoxic response to autoantigens, localization in orbital sites, and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-γ-secreting CD4+ CTLs in GO. Therefore, cytotoxic pathways may become potential therapeutic targets for GO.

CTL*

Pathogenesis

10.1038/s41423-020-00615-2

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Citations (64)

Downregulation of the long non-coding RNA MALAT1 in tenofovir-treated pregnant women with hepatitis B virus infection promotes immune recovery of natural killer cells via the has-miR-155-5p/HIF-1α axis

International Immunopharmacology (2022)

Fanfan Guo Yufei Yuan Ziyi Chen Fan Gao Xia Li

Currently, tenofovir disoproxil fumarate (TDF) treatment in pregnant women with hepatitis B virus (HBV) infection in the second trimester of pregnancy to reduce the HBV DNA load and block the mother-to-child transmission of HBV has become a consensus. An increasing number of studies have shown that lncRNAs play an important role in immune regulation; however, there are only a few studies on how lncRNAs affect the immune function of TDF-treated pregnant women with HBV infection.The peripheral blood of pregnant women with HBV infection was collected before and after TDF treatment for whole-transcriptome sequencing; the differential expression of lncRNA MALAT1 in PBMCs and natural killer (NK) cells was verified by qRT-PCR. ELISA and flow cytometry were used to detect the effect of MALAT1 on NK-92 cells on IFN-γ secretion. Dual-luciferase reporter, qRT-PCR, and western blot analyses were used to verify the relationship between the expression levels of MALAT1, has-miR-155-5p and HIF-1α.After TDF treatment, the MALAT1 expression in the PBMCs of pregnant women with HBV infection, especially in NK cells, was significantly reduced. MALAT1 overexpression decreased IFN-γ secretion in NK-92 cells, while IFN-γ secretion increased after MALAT1 knockdown. Mechanistically, we identified MALAT1 as a competitive endogenous RNA that regulates HIF-1α expression by sponging has-miR-155-5p. Low HIF-1α expression resulted in increased IFNG expression in, and IFN-γ secretion by, NK cells.Thus, MALAT1 may play an important role in NK cell-mediated immunity in TDF-treated pregnant women with HBV infection by regulating the has-miR-155-5p/HIF-1α axis.

MALAT1

10.1016/j.intimp.2022.108701

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Citations (9)

A system-level investigation into the pharmacological mechanisms of flavor compounds in Maotai liquor

Research Square (Research Square) (2020)

Zhigang Liu Wei Zhou Ziyi Chen Guohao Zhang

Abstract Maotai-flavor liquor, one of the world’s famous natural fermentation food product plays a significant role in traditional Chinese culture and people’s daily lives for a long time due to its good taste. However, the pharmacological activities of flavor compounds in Maotai liquor has not been fully elucidated. In answering this question, a system-level analysis was developed by combining in silico ADME evaluation, multi-target prediction, GO enrichment analysis, network pharmacology technology, pathway analysis, as well as experimental verification to elucidate the pharmacological effects of flavor compounds in Maotai liquor. Finally, 55 active compounds and 80 targets were identified to interpret the pharmacological effect of the flavor compounds. Moreover, the key active compounds was verified by in vitro experiments to validate the reliability of our approaches. Our study provides a novel integrated strategy to comprehensively understand the pharmacological activities of complex components in Maotai liquor.

ADME

Systems pharmacology

10.21203/rs.3.rs-15719/v1

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LncRNA ILF3-AS1 mediated the occurrence of epilepsy through suppressing hippocampal miR-212 expression

Aging (2020)

Xiaodong Cai Ling Long Chao Zeng Guanzhong Ni Yangyang Meng

Increased expression of some matrix metalloproteinases (MMPs) is closely associated with epilepsy.However, factors that promote their expression have not been clarified.Long noncoding RNAs (lncRNAs) play crucial roles in the development of human diseases, including various cancers, but its potential function in temporal lobe epilepsy (TLE) has remained unexplored.In this study, we showed that hippocampal and serum ILF3-AS1 levels are higher in TLE patients than in matched controls.Interleukin (IL)-1β and tumor necrosis factor (TNF)-α induced ILF3-AS1 expression in astrocytes, while ectopic expression of ILF3-AS1 enhanced IL-6 and TNF-α expression.Ectopic ILF3-AS1 in astrocytes also increased expression of MMP2, MMP3, MMP9 and MMP14, but suppressed expression of miR-212.Consistent with that finding, miR-212 levels were lower in the hippocampus and serum of TLE patients than their controls.This suggests that ILF3-AS1 promotes expression of inflammatory cytokines and MMPs by targeting miR-212 and that ILF3-AS1 plays a crucial role in the development of TLE.

MMP9

Ectopic expression

MMP3

MMP2

10.18632/aging.103148

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Citations (34)