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Xu L, Li J, Li L, Zhang Q, Feng Q, Bai L. Exploring miR-577 and miR-494-3p as Emerging Biomarkers in Sepsis-Associated Acute Kidney Injury: Diagnostic and Prognostic Perspectives. Microbiol Immunol 2025; 69:297-306. [PMID: 40089974 DOI: 10.1111/1348-0421.13210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/21/2025] [Accepted: 02/24/2025] [Indexed: 03/18/2025]
Abstract
Sepsis-associated acute kidney injury (AKI) poses a severe threat to patients' lives and health, making early predictions, intervention, and treatment crucial. This study aims to preliminarily explore the clinical role of miR-577 and miR-494-3p in sepsis-associated AKI. The study included 70 sepsis patients with AKI, 65 sepsis patients without AKI, and a healthy control group (HC, n = 67) to set baseline miRNA levels. Urinary miR-577 and miR-494-3p levels were measured using qRT-PCR. ROC curves evaluated their diagnostic value for sepsis-associated AKI. Logistic regression analyzed AKI risk factors, while Pearson correlation explored miRNA-clinical indicator links. Cox regression models and KM curves assessed the prognostic value of miRNAs in sepsis-associated AKI patients. Sepsis-associated AKI patients showed heightened inflammatory markers, renal indicators, and APACHE II scores compared to those without AKI. However, their urinary miR-577 and miR-494-3p levels were notably lower, distinguishing them with high diagnostic value. These miRNAs inversely correlated with inflammatory markers, renal indicators, and severity scores. Logistic regression showed lactate, PCT, BUN, Scr, Cys-C, NGAL, KIM-1, and APACHE II, as risk factors, while miR-577 and miR-494-3p were protective. In deceased sepsis-associated AKI patients, these miRNAs were lower, with higher inflammatory markers, renal indicators, and severity scores. miR-577 and miR-494-3p independently predicted mortality, with lower expressions linked to higher death rates. miR-577 and miR-494-3p are closely related to sepsis-associated AKI and can serve as potential biomarkers for diagnosis and prognostic assessment.
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Affiliation(s)
- Lixia Xu
- Department of Oncology Nursing, Hebei General Hospital, Hebei, China
| | - Jingpo Li
- Department of Urology Nursing, Hebei General Hospital, Hebei, China
| | - Li Li
- Department of Oncology Nursing, Hebei General Hospital, Hebei, China
| | - Qiushuang Zhang
- Department of Neurology Nursing, Hebei General Hospital, Hebei, China
| | - Qiuju Feng
- Department of Emergency and Critical Care, Hebei General Hospital, Hebei, China
| | - Lijie Bai
- Department of Coronary Intensive Care Unit CCU, Hebei General Hospital, Hebei, China
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Saadh MJ, Saeed TN, Alfarttoosi KH, Sanghvi G, Roopashree R, Thakur V, Lakshmi L, Kubaev A, Taher WM, Alwan M, Jawad MJ, Al-Nuaimi AMA. Exosomes and MicroRNAs: key modulators of macrophage polarization in sepsis pathophysiology. Eur J Med Res 2025; 30:298. [PMID: 40247413 PMCID: PMC12007276 DOI: 10.1186/s40001-025-02561-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Accepted: 04/06/2025] [Indexed: 04/19/2025] Open
Abstract
Sepsis is a highly dangerous and complex condition that can result in death. It is characterized by a strong reaction to an infection, causing dysfunction in multiple bodily systems and a high risk of mortality. The transformation of macrophages is a vital stage in the procedure as they possess the capability to interchange between two separate types: M1, which promotes inflammation, and M2, which inhibits inflammation. The choice greatly affects the immune response of the host. This analysis underscores the rapidly expanding roles of exosomes and microRNAs (miRNAs) in regulating the trajectory of macrophage polarization during episodes of sepsis. Exosomes, extremely small extracellular vesicles, facilitate cellular communication by transferring biologically active compounds, including miRNAs, proteins, and lipids. We investigate the impact of changes in exosome production and composition caused by sepsis on macrophage polarization and function. Unique microRNAs present in exosomes play a significant role in controlling crucial signaling pathways that govern the phenotype of macrophages. Through thorough examination of recent progress in this area, we clarify the ways in which miRNAs derived from exosomes can either aggravate or alleviate the inflammatory reactions that occur during sepsis. This revelation not only deepens our comprehension of the underlying mechanisms of sepsis, but it also reveals potential new biomarkers and targets for treatment. This assessment aims to amalgamate diverse research investigations and propose potential avenues for future investigations on the influence that exosomes and miRNAs have on macrophage polarization and the body's response to sepsis. These entities are essential for controlling the host's reaction to sepsis and hold important functions in this mechanism.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
| | - Tamara Nazar Saeed
- Department of Medical Laboratory Technics, College of Health and Medical Technology, Alnoor University, Mosul, Iraq.
| | | | - Gaurav Sanghvi
- Department of Microbiology, Faculty of Science, Marwadi University Research Center, Marwadi University, Rajkot, Gujarat, 360003, India
| | - R Roopashree
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to Be University), Bangalore, Karnataka, India
| | - Vishal Thakur
- Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, 140401, Punjab, India
| | - L Lakshmi
- Department of Nursing, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
| | - Aziz Kubaev
- Department of Maxillofacial Surgery, Samarkand State Medical University, 18 Amir Temur Street, 140100, Samarkand, Uzbekistan
| | - Waam Mohammed Taher
- College of Nursing, National University of Science and Technology, Dhi Qar, Iraq
| | - Mariem Alwan
- Pharmacy College, Al-Farahidi University, Baghdad, Iraq
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Jin Y, Zhang Y, Li Y, Zheng X. Significances of miRNAs for predicting sepsis mortality: a meta-analysis. Front Microbiol 2025; 16:1472124. [PMID: 40135054 PMCID: PMC11933020 DOI: 10.3389/fmicb.2025.1472124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 02/19/2025] [Indexed: 03/27/2025] Open
Abstract
Background Sepsis is a life-threatening condition caused by a dysregulated immune response to infection and remains a major cause of mortality in intensive care units (ICUs). Recent studies have identified microRNAs (miRNAs), a class of small RNA molecules, as potential biomarkers for diagnosing and predicting outcomes in sepsis patients. However, the results of these studies have been inconsistent. This meta-analysis aims to comprehensively evaluate the diagnostic and prognostic value of miRNAs in predicting sepsis-related mortality. Methods A comprehensive literature search was performed across major databases, including PubMed, Cochrane Library, EMBASE, and CNKI, up to April 7, 2024. Data extraction and meta-analysis were conducted using Meta-disk 1.4 and STATA 15.1, employing both fixed- and random-effects models to ensure robust statistical analysis. Results A total of 55 studies met the inclusion criteria and were analyzed. The pooled sensitivity, specificity, and area under the summary receiver operating characteristic (SROC) curve for miRNA detection were calculated. The overall performance of total miRNA detection demonstrated a sensitivity of 0.76 (95% confidence interval [CI]: 0.74-0.77), a specificity of 0.72 (95% CI: 0.71-0.73), and an SROC value of 0.83. Subgroup analyses revealed that miR-133a-3p exhibited the highest diagnostic accuracy, with a pooled sensitivity of 0.83 (95% CI: 0.70-0.92), specificity of 0.79 (95% CI: 0.71-0.86), and an SROC value of 0.90. Additionally, other miRNAs, including miR-146a, miR-21, miR-210, miR-223-3p, miR-155, miR-25, miR-122, miR-125a, miR-125b, and miR-150, also demonstrated high SROC values (0.84 to 0.76). Conclusion This meta-analysis underscores the potential of several microRNAs (miRNAs) as reliable biomarkers for predicting sepsis mortality. Specifically, miR-133a-3p, miR-146a, miR-21, miR-210, miR-223-3p, miR-155, miR-25, miR-122, miR-125b, and miR-150 emerge as promising candidates for clinical applications in sepsis prognosis.
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Affiliation(s)
| | | | | | - Xiaolan Zheng
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
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Rayat Pisheh H, Sani M. Mesenchymal stem cells derived exosomes: a new era in cardiac regeneration. Stem Cell Res Ther 2025; 16:16. [PMID: 39849585 PMCID: PMC11756228 DOI: 10.1186/s13287-024-04123-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 12/18/2024] [Indexed: 01/25/2025] Open
Abstract
Despite significant strides in medical treatments and surgical procedures for cardiovascular diseases, these conditions continue to be a major global health concern. The persistent need for innovative therapeutic approaches to mend damaged heart tissue highlights the complexity and urgency of this medical challenge. In recent years, stem cells have emerged as a promising tool for tissue regeneration, but challenges such as graft rejection and tumor formation have limited their clinical application. Exosomes, extracellular vesicles containing a diverse array of biomolecules, have garnered significant attention for their potential in regenerative medicine. The cardioprotective and reparative properties of mesenchymal stem cell-derived exosomes hold promise for the treatment of heart diseases. These exosomes can modulate various cellular processes, including angiogenesis, apoptosis, and inflammation, thereby enhancing cardiac function. Despite the growing interest, there remains a lack of comprehensive reviews synthesizing the molecular mechanisms, preclinical, and clinical evidence related to the specific role of MSC-derived exosomes in cardiac therapies. This review aims to fill that gap by exploring the potential of MSC-derived exosomes as a therapeutic strategy for cardiac diseases. This review explores the potential of mesenchymal stem cell-derived exosomes as a therapeutic strategy for cardiac diseases. We discuss the molecular mechanisms underlying their cardioprotective effects, summarize preclinical and clinical studies investigating their efficacy, and address the challenges and future perspectives of exosome-based therapies. The collective evidence suggests that MSC-derived exosomes hold promise as a novel and effective therapeutic approach for cardiac diseases.
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Affiliation(s)
- Hossein Rayat Pisheh
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Shiraz Institute for Stem Cell & Regenerative Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahsa Sani
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
- Shiraz Institute for Stem Cell & Regenerative Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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Lu Y, Wu H, Luo Y, Xia W, Sun D, Chen R, Miao Z, Zhang W, Yu Y, Wen A. CircIRAK3 Promotes Neutrophil Extracellular Trap Formation by Improving the Stability of ELANE mRNA in Sepsis. Inflammation 2024:10.1007/s10753-024-02206-z. [PMID: 39707013 DOI: 10.1007/s10753-024-02206-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 11/28/2024] [Accepted: 12/02/2024] [Indexed: 12/23/2024]
Abstract
Excessive formation of neutrophil extracellular traps (NETs) has been shown to exacerbate inflammatory injury and organ damage in patients with sepsis. Circular RNAs (circRNAs) abnormally expressed in immune cells of sepsis patients, and play an important role in the pathogenesis of dysregulated immune responses. However, the functions of circRNAs in NET formation during sepsis remain unknown. Here, we identified circIRAK3, a novel circRNA that was upregulated in peripheral blood neutrophils of sepsis patients. Combining clinical data, we revealed that elevated circIRAK3 was positively correlated with blood NET levels. Furthermore, knockdown and overexpression in differentiated HL-60 (dHL-60) neutrophil-like cells demonstrated that circIRAK3 promoted NET formation. In addition, we found that circIRAK3 promoted NET formation via positively regulating elastase expression in dHL-60 cells when treated with inflammatory stimuli. Mechanistically, circIRAK3 directly interacted with ELAVL1 to improve ELANE mRNA stability and consequently promote elastase protein expression. In summary, our study reveals that circIRAK3 promotes NET formation in sepsis by increasing ELANE mRNA levels.
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Affiliation(s)
- Yao Lu
- Department of Blood Transfusion, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Burns and Combined Injury, Army Medical University, NO 10, Changjiang Branch Road, Daping District, Chongqing, 400042, China
| | - Huang Wu
- Department of Blood Transfusion, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Burns and Combined Injury, Army Medical University, NO 10, Changjiang Branch Road, Daping District, Chongqing, 400042, China
| | - Yuanyuan Luo
- Department of Blood Transfusion Medicine, The First Medical Center of Chinese PLA General Hospital, NO 28, Fuxing Road, Haidian District, Beijing, 100853, China
| | - Wenjun Xia
- Department of Blood Transfusion, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Burns and Combined Injury, Army Medical University, NO 10, Changjiang Branch Road, Daping District, Chongqing, 400042, China
| | - Denglian Sun
- Department of Blood Transfusion, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Burns and Combined Injury, Army Medical University, NO 10, Changjiang Branch Road, Daping District, Chongqing, 400042, China
| | - Ruichi Chen
- Department of Blood Transfusion, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Burns and Combined Injury, Army Medical University, NO 10, Changjiang Branch Road, Daping District, Chongqing, 400042, China
| | - Zeqing Miao
- Department of Blood Transfusion, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Burns and Combined Injury, Army Medical University, NO 10, Changjiang Branch Road, Daping District, Chongqing, 400042, China
| | - Weiwei Zhang
- Department of Blood Transfusion, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Burns and Combined Injury, Army Medical University, NO 10, Changjiang Branch Road, Daping District, Chongqing, 400042, China
| | - Yang Yu
- Department of Blood Transfusion Medicine, The First Medical Center of Chinese PLA General Hospital, NO 28, Fuxing Road, Haidian District, Beijing, 100853, China.
| | - Aiqing Wen
- Department of Blood Transfusion, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Burns and Combined Injury, Army Medical University, NO 10, Changjiang Branch Road, Daping District, Chongqing, 400042, China.
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Yan W, Yan Y, Luo X, Dong Y, Liang G, Miao H, Huang Z, Jiang H. Lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells is inhibited by microRNA-494-3p via targeting lipoprotein-associated phospholipase A2. Eur J Trauma Emerg Surg 2024; 50:3289-3298. [PMID: 38955820 PMCID: PMC11666615 DOI: 10.1007/s00068-024-02588-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 06/14/2024] [Indexed: 07/04/2024]
Abstract
BACKGROUND Gram-negative bacterial lipopolysaccharide (LPS) is a major component of inflammation and plays a key role in the pathogenesis of sepsis. According to our previous study, the expression of lipoprotein-associated phospholipase A2 (Lp-PLA2) is significantly upregulated in septic patients and is positively correlated with the severity of this disease. Herein, we investigated the potential roles of Lp-PLA2-targeting microRNAs (miRNAs) in LPS-induced inflammation in murine mononuclear macrophages (RAW264.7 cells). METHODS In LPS-stimulated RAW264.7 cells, Lp-PLA2 was confirmed to be expressed during the inflammatory response. The function of microRNA-494-3p (miR-494-3p) in the LPS-induced inflammatory response of RAW264.7 cells was determined by the transfection of a miR-494-3p mimic or inhibitor in vitro. RESULTS Compared to the control, LPS induced a significant increase in the Lp-PLA2 level, which was accompanied by the release of inflammatory mediators. The bioinformatics and qRT‒PCR results indicated that the miR-494-3p level was associated with Lp-PLA2 expression in the LPS-induced inflammatory response of RAW264.7 cells. Dual-luciferase reporter assay results confirmed that the 3'-UTR of Lp-PLA2 was a functional target of microRNA-494-3p. During the LPS-induced inflammatory response of RAW264.7 cells, targeting Lp-PLA2 and transfecting miR-494-3p mimics significantly upregulated the expression of miR-494-3p, leading to a reduction in the release of inflammatory factors and conferring a protective effect on LPS-stimulated RAW264.7 cells. CONCLUSION By targeting Lp-PLA2, miR-494-3p suppresses Lp-PLA2 secretion, thereby alleviating LPS-induced inflammation, which indicates that miR-494-3p may be a potential target for sepsis treatment.
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Affiliation(s)
- Wenxiao Yan
- Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, China
- Medical School of Nantong University, Nantong University, Nantong, China
| | - Yan Yan
- Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, China
- Medical School of Nantong University, Nantong University, Nantong, China
- Department of Intensive Care Unit, Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Xinye Luo
- Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, China
- Medical School of Nantong University, Nantong University, Nantong, China
| | - Yansong Dong
- Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, China
- Medical School of Nantong University, Nantong University, Nantong, China
| | - Guiwen Liang
- Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, China
- Medical School of Nantong University, Nantong University, Nantong, China
| | - Hua Miao
- Medical School of Nantong University, Nantong University, Nantong, China.
- Department of Emergency Medicine, Rudong County People's Hospital, Nantong, China.
| | - Zhongwei Huang
- Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, China.
- Medical School of Nantong University, Nantong University, Nantong, China.
| | - Haiyan Jiang
- Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, China.
- Medical School of Nantong University, Nantong University, Nantong, China.
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Mo Q, Mo Q, Mo F. Single-cell RNA sequencing and transcriptomic analysis reveal key genes and regulatory mechanisms in sepsis. Biotechnol Genet Eng Rev 2024; 40:1636-1658. [PMID: 37017187 DOI: 10.1080/02648725.2023.2196475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 03/17/2023] [Indexed: 04/06/2023]
Abstract
The pathogenesis of sepsis, with a high mortality rate and often poor prognosis, has not been fully elucidated. Therefore, an in-depth study on the pathogenesis of sepsis at the molecular level is essential to identify key sepsis-related genes. The aim of this study was to explore the key genes and potential molecular mechanisms of sepsis using a bioinformatics approach. In addition, key genes with miRNA network correlation analysis and immune infiltration correlation analysis were investigated. The scRNA dataset (GSE167363) and RNA-seq dataset (GSE65682, GSE134347) from GEO database were used for screening out differentially expressed genes using single-cell sequencing and transcriptome sequencing. The analysis of immune infiltration was evaluated by the CIBERSORT method. Key genes and possible mechanisms were identified by WGCNA analysis, GSVA analysis, GSEA enrichment analysis and regulatory network analysis, and miRNA networks associated with key genes were constructed. Nine key genes associated with the development of sepsis, namely IL7R, CD3D, IL32, GPR183, HLA-DPB1, CD81, PEBP1, NCL, and ETS1 were screened, and the specific signaling mechanisms associated with the key genes causing sepsis were predicted. Immune profiling showed immune heterogeneity between control and sepsis samples. A regulatory network of 82 miRNAs, 266 pairs of mRNA-miRNA relationship pairs was also constructed. These nine key genes have the potential to become biomarkers for the diagnosis of sepsis and provide new targets and research directions for the treatment of sepsis.
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Affiliation(s)
- Qingping Mo
- Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Qingying Mo
- Shuda College, Hunan Normal University, Changsha, Hunan, China
| | - Fansen Mo
- University of South China, Hengyang, Hunan, China
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He Y, Liu Z, Li S, Liao S, Tang B, Lin Y. A Tetrahedral Framework DNA-Based Bioswitchable miR-150 Delivery System for Sepsis. ACS APPLIED MATERIALS & INTERFACES 2024; 16:58477-58488. [PMID: 39422161 DOI: 10.1021/acsami.4c14928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
Sepsis is a disease with high morbidity and mortality, for which effective treatments are lacking. In recent years, microRNAs (miRs) have been shown to regulate numerous biological processes and can function as therapeutic options for various diseases. However, the poor stability and cell entry properties of miRs have greatly limited their clinical application. In this study, we developed a tetrahedral framework nucleic acid (tFNA)-based bioswitchable miR delivery system (BiRDS) to deliver miR-150 for the treatment of sepsis. BiRDS showed anti-inflammatory effects both in vitro and in vivo by regulating the NF-κB and Notch1 pathways. Therefore, this system holds promise as an ideal candidate for tackling systemic inflammation and multiorgan dysfunction in septic patients in the future.
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Affiliation(s)
- Yutian He
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Zhiqiang Liu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Songhang Li
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Shengnan Liao
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Bicai Tang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yunfeng Lin
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
- Sichuan Provincial Engineering Research Center of Oral Biomaterials, Chengdu, Sichuan 610041, China
- National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
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Cheng Y, Liang Y, Tan X, Liu L. Host long noncoding RNAs in bacterial infections. Front Immunol 2024; 15:1419782. [PMID: 39295861 PMCID: PMC11408731 DOI: 10.3389/fimmu.2024.1419782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 08/15/2024] [Indexed: 09/21/2024] Open
Abstract
Bacterial infections remain a significant global health concern, necessitating a comprehensive understanding of the intricate host-pathogen interactions that play a critical role in the outcome of infectious diseases. Recent investigations have revealed that noncoding RNAs (ncRNAs) are key regulators of these complex interactions. Among them, long noncoding RNAs (lncRNAs) have gained significant attention because of their diverse regulatory roles in gene expression, cellular processes and the production of cytokines and chemokines in response to bacterial infections. The host utilizes lncRNAs as a defense mechanism to limit microbial pathogen invasion and replication. On the other hand, some host lncRNAs contribute to the establishment and maintenance of bacterial pathogen reservoirs within the host by promoting bacterial pathogen survival, replication, and dissemination. However, our understanding of host lncRNAs in the context of bacterial infections remains limited. This review focuses on the impact of host lncRNAs in shaping host-pathogen interactions, shedding light on their multifaceted functions in both host defense and bacterial survival, and paving the way for future research aimed at harnessing their regulatory potential for clinical applications.
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Affiliation(s)
- Yong Cheng
- Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK, United States
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, United States
| | - Yurong Liang
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, United States
- Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, United States
| | - Xuejuan Tan
- Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK, United States
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, United States
| | - Lin Liu
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, United States
- Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, United States
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Zhu C, Zhang L, Ding X, Wu W, Zou J. Non-coding RNAs as regulators of autophagy in chondrocytes: Mechanisms and implications for osteoarthritis. Ageing Res Rev 2024; 99:102404. [PMID: 38971322 DOI: 10.1016/j.arr.2024.102404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 06/22/2024] [Accepted: 07/01/2024] [Indexed: 07/08/2024]
Abstract
Osteoarthritis (OA) is a chronic degenerative joint disease with multiple causative factors such as aging, mechanical injury, and obesity. Autophagy is a complex dynamic process that is involved in the degradation and modification of intracellular proteins and organelles under different pathophysiological conditions. Autophagy, as a cell survival mechanism under various stress conditions, plays a key role in regulating chondrocyte life cycle metabolism and cellular homeostasis. Non-coding RNAs (ncRNAs) are heterogeneous transcripts that do not possess protein-coding functions, but they can act as effective post-transcriptional and epigenetic regulators of gene and protein expression, thus participating in numerous fundamental biological processes. Increasing evidence suggests that ncRNAs, autophagy, and their crosstalk play crucial roles in OA pathogenesis. Therefore, we summarized the complex role of autophagy in OA chondrocytes and focused on the regulatory role of ncRNAs in OA-associated autophagy to elucidate the complex pathological mechanisms of the ncRNA-autophagy network in the development of OA, thus providing new research targets for the clinical diagnosis and treatment of OA.
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Affiliation(s)
- Chenyu Zhu
- School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China
| | - Lingli Zhang
- School of Athletic Performance, Shanghai University of Sport, Shanghai 200438, China
| | - Xiaoqing Ding
- School of Athletic Performance, Shanghai University of Sport, Shanghai 200438, China
| | - Wei Wu
- School of Athletic Performance, Shanghai University of Sport, Shanghai 200438, China.
| | - Jun Zou
- School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China.
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Anada N, Nakayama Y, Takeshita J, Kageyama K, Sakamoto H, Kamibayashi T, Nakajima Y. Role of MicroRNA-21 in Regulating Intracellular Pathways Associated With Phagocytosis in Human Macrophages: An In Vitro Study. Cureus 2024; 16:e63736. [PMID: 39100039 PMCID: PMC11295782 DOI: 10.7759/cureus.63736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/03/2024] [Indexed: 08/06/2024] Open
Abstract
Introduction The efficient clearance of bacteria by macrophages is crucial for the timely resolution of inflammation. In this study, we investigated the role of microRNA-21 (miR-21)-induced phagocytosis and its intracellular signaling pathways in human macrophages in vitro. Methods Human peripheral blood mononuclear cells (PBMCs) were isolated from whole blood collected from 15 healthy volunteers. Differentiated human macrophages were incubated with lipopolysaccharide (LPS) to determine the time course of changes in phagocytic activity and miR-21 expression. The expression of candidate genes targeted by miR-21 and its downstream effectors was quantitatively assessed. The effects of miR-21 modulation were also examined via transfection with miR-21 mimics and inhibitors. Results Incubation of human macrophages with LPS upregulated both phagocytosis and miR-21 expression. Notably, changing miR-21 expression levels using miR-21 mimics or inhibitors led to significant and opposite changes in the expression of its downstream effectors. miR-21 induction in macrophages downregulated PDCD4 and PTEN, promoted the phosphorylation of Akt and the production of the anti-inflammatory cytokine IL-10, and facilitated phagocytosis. Conclusion This study directly confirms that LPS upregulates macrophage phagocytosis and miR-21 expression. Elevated miR-21 levels in macrophages enhanced phagocytosis, contributing to an anti-inflammatory phenotype. These findings underscore the importance of miR-21 in resolving inflammation.
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Affiliation(s)
- Natsuki Anada
- Anesthesiology and Intensive Care Medicine, Kansai Medical University, Hirakata, JPN
| | - Yoshinobu Nakayama
- Anesthesiology and Critical Care, Faculty of Medicine, Kindai University, Osakasayama, JPN
| | - Jun Takeshita
- Anesthesiology and Critical Care, Osaka Women's and Children's Hospital, Osaka, JPN
| | - Kyoko Kageyama
- Anesthesiology and Intensive Care Medicine, Kansai Medical University, Hirakata, JPN
| | - Hiroatsu Sakamoto
- Anesthesiology and Critical Care, Faculty of Medicine, Kindai University, Osakasayama, JPN
| | - Takahiko Kamibayashi
- Anesthesiology and Intensive Care Medicine, Kansai Medical University, Hirakata, JPN
| | - Yasufumi Nakajima
- Anesthesiology and Critical Care, Faculty of Medicine, Kindai University, Osakasayama, JPN
- Outcomes Research Consortium, Cleveland Clinic, Cleveland, USA
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Wang J, Zhang J, Liu H, Meng L, Gao X, Zhao Y, Wang C, Gao X, Fan A, Cao T, Fan D, Zhao X, Lu Y. N6-methyladenosine reader hnRNPA2B1 recognizes and stabilizes NEAT1 to confer chemoresistance in gastric cancer. Cancer Commun (Lond) 2024; 44:469-490. [PMID: 38512764 PMCID: PMC11024687 DOI: 10.1002/cac2.12534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 02/29/2024] [Accepted: 03/06/2024] [Indexed: 03/23/2024] Open
Abstract
BACKGROUND Chemoresistance is a major cause of treatment failure in gastric cancer (GC). Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is an N6-methyladenosine (m6A)-binding protein involved in a variety of cancers. However, whether m6A modification and hnRNPA2B1 play a role in GC chemoresistance is largely unknown. In this study, we aimed to investigate the role of hnRNPA2B1 and the downstream mechanism in GC chemoresistance. METHODS The expression of hnRNPA2B1 among public datasets were analyzed and validated by quantitative PCR (qPCR), Western blotting, immunofluorescence, and immunohistochemical staining. The biological functions of hnRNPA2B1 in GC chemoresistance were investigated both in vitro and in vivo. RNA sequencing, methylated RNA immunoprecipitation, RNA immunoprecipitation, and RNA stability assay were performed to assess the association between hnRNPA2B1 and the binding RNA. The role of hnRNPA2B1 in maintenance of GC stemness was evaluated by bioinformatic analysis, qPCR, Western blotting, immunofluorescence, and sphere formation assays. The expression patterns of hnRNPA2B1 and downstream regulators in GC specimens from patients who received adjuvant chemotherapy were analyzed by RNAscope and multiplex immunohistochemistry. RESULTS Elevated expression of hnRNPA2B1 was found in GC cells and tissues, especially in multidrug-resistant (MDR) GC cell lines. The expression of hnRNPA2B1 was associated with poor outcomes of GC patients, especially in those who received 5-fluorouracil treatment. Silencing hnRNPA2B1 effectively sensitized GC cells to chemotherapy by inhibiting cell proliferation and inducing apoptosis both in vitro and in vivo. Mechanically, hnRNPA2B1 interacted with and stabilized long noncoding RNA NEAT1 in an m6A-dependent manner. Furthermore, hnRNPA2B1 and NEAT1 worked together to enhance the stemness properties of GC cells via Wnt/β-catenin signaling pathway. In clinical specimens from GC patients subjected to chemotherapy, the expression levels of hnRNPA2B1, NEAT1, CD133, and CD44 were markedly elevated in non-responders compared with responders. CONCLUSION Our findings indicated that hnRNPA2B1 interacts with and stabilizes lncRNA NEAT1, which contribute to the maintenance of stemness property via Wnt/β-catenin pathway and exacerbate chemoresistance in GC.
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Affiliation(s)
- Jiayao Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive DiseasesXijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxiP. R. China
- The Air Force Hospital of Southern Theater CommandGuangzhouGuangdongP. R. China
| | - Jiehao Zhang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive DiseasesXijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxiP. R. China
- The Air Force Hospital of Southern Theater CommandGuangzhouGuangdongP. R. China
| | - Hao Liu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive DiseasesXijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxiP. R. China
| | - Lingnan Meng
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive DiseasesXijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxiP. R. China
- National Center for International Research of Bio‐targeting TheranosticsGuangxi Key Laboratory of Bio‐targeting TheranosticsGuangxi Medical UniversityNanningGuangxiP. R. China
| | - Xianchun Gao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive DiseasesXijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxiP. R. China
| | - Yihan Zhao
- Second Clinical CollegeShaanxi University of Traditional Chinese MedicineXianyangShaanxiP. R. China
| | - Chen Wang
- College of Life SciencesNorthwest UniversityXi'anShaanxiP. R. China
| | - Xiaoliang Gao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive DiseasesXijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxiP. R. China
| | - Ahui Fan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive DiseasesXijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxiP. R. China
| | - Tianyu Cao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive DiseasesXijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxiP. R. China
| | - Daiming Fan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive DiseasesXijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxiP. R. China
| | - Xiaodi Zhao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive DiseasesXijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxiP. R. China
| | - Yuanyuan Lu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive DiseasesXijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxiP. R. China
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Wang Y, Zhang C, Liu T, Yu Z, Wang K, Ying J, Wang Y, Zhu T, Li J, Hu XL, Zhou Y, Lu G. Malat1 regulates PMN-MDSC expansion and immunosuppression through p-STAT3 ubiquitination in sepsis. Int J Biol Sci 2024; 20:1529-1546. [PMID: 38385073 PMCID: PMC10878150 DOI: 10.7150/ijbs.92267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 01/29/2024] [Indexed: 02/23/2024] Open
Abstract
Myeloid-derived suppressor cells (MDSCs) expand during sepsis and contribute to the development of persistent inflammation-immunosuppression-catabolism syndrome. However, the underlying mechanism remains unclear. Exploring the mechanisms of MDSCs generation may provide therapeutic targets for improving immune status in sepsis. Here, a sepsis mouse model is established by cecal ligation and perforation. Bone marrow cells at different sepsis time points are harvested to detect the proportion of MDSCs and search for differentially expressed genes by RNA-sequence. In lethal models of sepsis, polymorphonuclear-MDSCs (PMN-MDSCs) decrease in early but increase and become activated in late sepsis, which is contrary to the expression of metastasis-associated lung adenocarcinoma transcript 1 (Malat1). In vivo, Malat1 inhibitor significantly increases the mortality in mice with late sepsis. And in vitro, Malat1 down-regulation increases the proportion of PMN-MDSCs and enhanced its immunosuppressive ability. Mechanistically, Malat1 limits the differentiation of PMN-MDSCs by accelerating the degradation of phosphorylated STAT3. Furthermore, Stattic, an inhibitor of STAT3 phosphorylation, improves the survival of septic mice by inhibiting PMN-MDSCs. Overall, the study identifies a novel insight into the mechanism of sepsis-induced MDSCs and provides more evidence for targeting MDSCs in the treatment of sepsis.
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Affiliation(s)
- Yaodong Wang
- Department of Critical Care Medicine, Children's Hospital of Fudan University, Shanghai, China
| | - Caiyan Zhang
- Department of Critical Care Medicine, Children's Hospital of Fudan University, Shanghai, China
| | - Tingyan Liu
- Department of Critical Care Medicine, Children's Hospital of Fudan University, Shanghai, China
| | - Zhenhao Yu
- Department of Critical Care Medicine, Children's Hospital of Fudan University, Shanghai, China
| | - Kexin Wang
- Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Jiayun Ying
- Department of Critical Care Medicine, Children's Hospital of Fudan University, Shanghai, China
| | - Yao Wang
- Department of Critical Care Medicine, Children's Hospital of Fudan University, Shanghai, China
| | - Ting Zhu
- Department of Critical Care Medicine, Children's Hospital of Fudan University, Shanghai, China
| | - Jingjing Li
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| | - Xiuchuan Lucas Hu
- Lungs for Living Research Centre, UCL Respiratory, University College London, London, UK
| | - Yufeng Zhou
- Department of Critical Care Medicine, Children's Hospital of Fudan University, Shanghai, China
- Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
- National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China
- Fujian Key Laboratory of Neonatal Diseases, Fujian, China
| | - Guoping Lu
- Department of Critical Care Medicine, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
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Almalki WH. NEAT1 in inflammatory infectious diseases: An integrated perspective on molecular modulation. Pathol Res Pract 2024; 254:154956. [PMID: 38218038 DOI: 10.1016/j.prp.2023.154956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/13/2023] [Accepted: 11/15/2023] [Indexed: 01/15/2024]
Abstract
The long non-coding RNA (lncRNA), NEAT1, has emerged as a central figure in the intricate network of molecular regulators in inflammatory infectious diseases (IIDs). The review initiates a comprehensive exploration of NEAT1's multifaceted roles and molecular interactions in the context of these complex diseases. The study begins by acknowledging the global health burden of IIDs, underscoring the urgency for innovative insights into their pathogenesis and therapeutic avenues. NEAT1 is introduced as a pivotal lncRNA with growing relevance in immune responses and inflammatory processes. The core of this review unravels the NEAT1 landscape, elucidating its involvement in the modulation of immune signalling pathways, regulation of inflammatory cytokines, and interactions with various immune cells during infection. It explores NEAT1's role in orchestrating immune responses and balancing host defence mechanisms with the risk of immunopathology. Furthermore, the review underscores the clinical significance of NEAT1 in infectious diseases, discussing its associations with disease severity, prognosis, and potential as a diagnostic and therapeutic target. It provides insights into ongoing research endeavours aimed at harnessing NEAT1 for innovative disease management strategies, including developing RNA-based therapeutics. Concluding on a forward-looking note, the review highlights the broader implications of NEAT1 in the context of emerging infectious diseases and the possibility for precision medicine approaches that leverage NEAT1's regulatory capacities. In summary, this review illuminates the pivotal role of NEAT1 in IIDs by navigating its complex landscape, offering profound insights into its implications for disease pathogenesis and the development of targeted therapies.
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Affiliation(s)
- Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.
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15
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Xu LJ, Yang Y, Yuan LF, Liu H, Xu NP, Yang Y, Huang L. SP1-stimulated miR-208a-5p aggravates sepsis-induced myocardial injury via targeting XIAP. Exp Cell Res 2024; 435:113905. [PMID: 38163563 DOI: 10.1016/j.yexcr.2023.113905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 12/28/2023] [Accepted: 12/30/2023] [Indexed: 01/03/2024]
Abstract
The development of sepsis can lead to many organ dysfunction and even death. Myocardial injury is one of the serious complications of sepsis leading to death. New evidence suggests that microRNAs (miRNAs) play a critical role in infection myocardial injury. However, the mechanism which miR-208a-5p regulates sepsis-induced myocardial injury remains unclear. To mimic sepsis-induced myocardial injury in vitro, rat primary cardiomyocytes were treated with LPS. Cell viability and apoptosis were tested by CCK-8 and flow cytometry, respectively. The secretion of inflammatory factors was analyzed by ELISA. mRNA and protein levels were detected by RT-qPCR and Western blotting. The interaction among SP1, XIAP and miR-208a-5p was detected using dual luciferase report assay. Ultrasonic analysis and HE staining was performed to observe the effect of miR-208a-5p in sepsis-induced rats. Our findings indicated that miR-208a-5p expression in primary rat cardiomyocytes was increased by LPS. MiR-208a-5p inhibitor reversed LPS-induced cardiomyocytes injury through inhibiting the apoptosis. Furthermore, the inflammatory injury in cardiomyocytes was induced by LPS, which was rescued by miR-208a-5p inhibitor. In addition, downregulation of miR-208a-5p improved LPS-induced sepsis myocardial injury in vivo. Mechanistically, XIAP might be a target gene of miR-208a-5p. SP1 promoted transcription of miR-208a by binding to the miR-208a promoter region. Moreover, silencing of XIAP reversed the regulatory of miR-208a-5p inhibitor on cardiomyocytes injury. To sum up, those findings revealed silencing of miR-208a-5p could alleviate sepsis-induced myocardial injury, which would grant a new process for the treatment of sepsis.
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Affiliation(s)
- Ling-Jun Xu
- Department of Emergency, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, PR China; Department of Emergency, Jiangxi Provincial Children's Hospital, Nanchang 330038, Jiangxi Province, PR China
| | - Yixian Yang
- Department of Emergency, Jiangxi Provincial Children's Hospital, Nanchang 330038, Jiangxi Province, PR China
| | - Ling-Feng Yuan
- Department of Function, Jiangxi Provincial Children's Hospital, Nanchang 330038, Jiangxi Province, PR China
| | - Hong Liu
- Department of Emergency, Jiangxi Provincial Children's Hospital, Nanchang 330038, Jiangxi Province, PR China
| | - Nan-Ping Xu
- Department of Emergency, Jiangxi Provincial Children's Hospital, Nanchang 330038, Jiangxi Province, PR China
| | - Yu Yang
- Department of Endocrinology, Metabolism and Genetics, Jiangxi Provincial Children's Hospital, Nanchang 330038, Jiangxi Province, PR China.
| | - Liang Huang
- Department of Emergency, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, PR China.
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16
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Wang L, Wang H, Luo Y, Wu W, Gui Y, Zhao J, Xiong R, Li X, Yuan D, Yuan C. Role of LncRNA MIAT in Diabetic Complications. Curr Med Chem 2024; 31:1716-1725. [PMID: 37711129 DOI: 10.2174/0929867331666230914091944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 06/21/2023] [Accepted: 07/25/2023] [Indexed: 09/16/2023]
Abstract
Long non-coding RNA (LncRNA) refers to a large class of RNAs with over 200 nucleotides that do not have the function of encoding proteins. In recent years, more and more literature has revealed that lncRNA is involved in manipulating genes related to human health and disease, playing outstanding biological functions, which has attracted widespread attention from researchers. The newly discovered long-stranded non-coding RNA myocardial infarction-related transcript (LncRNA MIAT) is abnormally expressed in a variety of diseases, especially in diabetic complications, and has been proven to have a wide range of effects. This review article aimed to summarize the importance of LncRNA MIAT in diabetic complications, such as diabetic cardiomyopathy, diabetic nephropathy, and diabetic retinopathy, and highlight the latest findings on the pathway and mechanism of its participation in regulating diabetic complications, which may aid in finding new intervention targets for the treatment of diabetic complications. LncRNA MIAT competitively binds microRNAs to regulate gene expression as competitive endogenous RNAs. Thus, this review article has reviewed the biological function and pathogenesis of LncRNA MIAT in diabetic complications and described its role in diabetic complications. This paper will help in finding new therapeutic targets and intervention strategies for diabetes complications.
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Affiliation(s)
- Lijun Wang
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, China
- College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China
| | - Hailin Wang
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, China
- College of Medicine and Health Science, China Three Gorges University, Yichang, 443002, China
| | - Yiyang Luo
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, China
- College of Medicine and Health Science, China Three Gorges University, Yichang, 443002, China
| | - Wei Wu
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, China
- College of Medicine and Health Science, China Three Gorges University, Yichang, 443002, China
| | - Yibei Gui
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, China
- College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China
| | - Jiale Zhao
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, China
- College of Medicine and Health Science, China Three Gorges University, Yichang, 443002, China
| | - Ruisi Xiong
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, China
- College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China
| | - Xueqin Li
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, China
- College of Medicine and Health Science, China Three Gorges University, Yichang, 443002, China
| | - Ding Yuan
- College of Medicine and Health Science, China Three Gorges University, Yichang, 443002, China
| | - Chengfu Yuan
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, China
- College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China
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Tian T, Li S, Luo H, Li Y, Chen H, Yang Y, Chen G, Xie B, Yan Z, Wang Z, Li L, Jiang Y. LILAR, a novel long noncoding RNA regulating autophagy in the liver tissues of endotoxemic mice through a competing endogenous RNA mechanism. MedComm (Beijing) 2023; 4:e398. [PMID: 37829506 PMCID: PMC10565381 DOI: 10.1002/mco2.398] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 09/07/2023] [Accepted: 09/14/2023] [Indexed: 10/14/2023] Open
Abstract
Sepsis is an often-deadly complication of infection that can lead to multiple organ failure. Previous studies have demonstrated that autophagy has a protective effect on liver injury in sepsis. Here, we report a novel long noncoding RNA (lncRNA), named lipopolysaccharide (LPS)-induced liver autophagy regulator (LILAR), which was highly induced in the liver tissues of endotoxemic mice. LILAR deficiency significantly increased the susceptibility of mice to LPS. In contrast, LILAR overexpression rescued the liver injury mediated by LILAR deficiency and increased the survival of LILAR knockout mice with endotoxemia. Autophagy-related protein 13 (Atg13) is a potential downstream target gene of LILAR. LILAR deficiency notably decreased Atg13 expression and suppressed autophagy in the livers of mice challenged with LPS. A reporter gene assay showed that LILAR competitively adsorbed miR-705 to increase the expression of Atg13 in cultured cells, indicating that LILAR participates in the regulation of the autophagy in the liver tissues of endotoxemic mice through a competitive endogenous RNA mechanism. In summary, we identified a novel lncRNA, LILAR, as a hepatic autophagy regulator, which not only promotes our understanding of liver pathophysiology but also provides a potential therapeutic target and/or diagnostic biomarker for liver injury in endotoxemia.
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Affiliation(s)
- Tian Tian
- Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdongChina
| | - Shan Li
- Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdongChina
| | - Haihua Luo
- Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdongChina
| | - Yijing Li
- Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdongChina
| | - Hanghang Chen
- Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdongChina
| | - Ying Yang
- Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdongChina
| | - Guangqin Chen
- Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdongChina
| | - Bingyao Xie
- Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdongChina
| | - Zhengzheng Yan
- Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdongChina
| | - Zhenqi Wang
- Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdongChina
| | - Lei Li
- Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdongChina
| | - Yong Jiang
- Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdongChina
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18
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Ghafouri-Fard S, Abbasi F, Nicknam A, Hussen BM, Eslami S, Akbari Dilmaghani N, Taheri M, Sharifi G. Dysregulation of PVT1 and NEAT1 lncRNAs in pituitary adenomas. Pathol Res Pract 2023; 248:154573. [PMID: 37270938 DOI: 10.1016/j.prp.2023.154573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 05/23/2023] [Accepted: 05/24/2023] [Indexed: 06/06/2023]
Abstract
Pituitary adenomas are slow-growing tumors originated from the anterior part of pituitary gland. These tumors are associated with dysregulation of a number of long non-coding RNAs (lncRNAs). PVT1, TUG1, MALAT1, NEAT1 and GAS5 are among lncRNAs with important roles in the regulation of cell proliferation, cell apoptosis, cell differentiation and cell cycle transition. In the current study, we assessed expression levels of PVT1, TUG1, MALAT1, NEAT1 and GAS5 in the pituitary adenoma samples compared with adjacent non-cancerous samples to find their relevance with this type of tumors and their potential as diagnostic markers in these tumors. Expression of NEAT1 was significantly higher in total adenoma tissues (Expression ratio (95% CI)= 7.06 (2.31-21.4), P value= 0.02) and in non-functioning pituitary adenoma (NFPA) samples (Expression ratio (95% CI)= 8.5 (2.17-33.12), P value= 0.04) compared with corresponding controls. Although both lncRNAs had appropriate sensitivity values for discrimination of NFPAs from adjacent non-cancerous tissues (0.84 and 0.90 for PVT1 and NEAT1, respectively), the calculated AUC values were not adequate for either lncRNAs (0.63 ± 0.04 and 0.58 ± 0.04 for PVT1 and NEAT1, respectively). Therefore, NEAT1 and PVT1 lncRNAs are dysregulated in NFPA. The current study suggests the role of NEAT1 and PVT1 in the pathogenesis of NFPA.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzaneh Abbasi
- School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Amir Nicknam
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Kurdistan Region, Iraq
| | - Solat Eslami
- Department of Medical Biotechnology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran; Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Nader Akbari Dilmaghani
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Institute of Human Genetics, Jena University Hospital, Jena, Germany; Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Guive Sharifi
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Khan MJ, Singh P, Jha P, Nayek A, Malik MZ, Bagler G, Kumar B, Ponnusamy K, Ali S, Chopra M, Dohare R, Singh IK, Syed MA. Investigating the link between miR-34a-5p and TLR6 signaling in sepsis-induced ARDS. 3 Biotech 2023; 13:282. [PMID: 37496978 PMCID: PMC10366072 DOI: 10.1007/s13205-023-03700-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 05/10/2023] [Indexed: 07/28/2023] Open
Abstract
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are lung complications diagnosed by impaired gaseous exchanges leading to mortality. From the diverse etiologies, sepsis is a prominent contributor to ALI/ARDS. In the present study, we retrieved sepsis-induced ARDS mRNA expression profile and identified 883 differentially expressed genes (DEGs). Next, we established an ARDS-specific weighted gene co-expression network (WGCN) and picked the blue module as our hub module based on highly correlated network properties. Later we subjected all hub module DEGs to form an ARDS-specific 3-node feed-forward loop (FFL) whose highest-order subnetwork motif revealed one TF (STAT6), one miRNA (miR-34a-5p), and one mRNA (TLR6). Thereafter, we screened a natural product library and identified three lead molecules that showed promising binding affinity against TLR6. We then performed molecular dynamics simulations to evaluate the stability and binding free energy of the TLR6-lead molecule complexes. Our results suggest these lead molecules may be potential therapeutic candidates for treating sepsis-induced ALI/ARDS. In-silico studies on clinical datasets for sepsis-induced ARDS indicate a possible positive interaction between miR-34a and TLR6 and an antagonizing effect on STAT6 to promote inflammation. Also, the translational study on septic mice lungs by IHC staining reveals a hike in the expression of TLR6. We report here that miR-34a actively augments the effect of sepsis on lung epithelial cell apoptosis. This study suggests that miR-34a promotes TLR6 to heighten inflammation in sepsis-induced ALI/ARDS. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-023-03700-1.
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Affiliation(s)
- Mohd Junaid Khan
- Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, 110025 India
| | - Prithvi Singh
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025 India
| | - Prakash Jha
- Laboratory of Molecular Modeling and Anticancer Drug Development, Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, New Delhi, 110007 India
| | - Arnab Nayek
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Md. Zubbair Malik
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, 15462 Kuwait City, Kuwait
| | - Ganesh Bagler
- Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, 110020 India
| | - Bhupender Kumar
- Department of Microbiology, Swami Shraddhanand College, University of Delhi, New Delhi, 110036 India
| | - Kalaiarasan Ponnusamy
- Biotechnology and Viral Hepatitis Division, National Centre for Disease Control, Sham Nath Marg, New Delhi, 110054 India
| | - Shakir Ali
- Department of Biochemistry, School of Chemical and Life Sciences Jamia Hamdard, New Delhi, 110062 India
| | - Madhu Chopra
- Laboratory of Molecular Modeling and Anticancer Drug Development, Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, New Delhi, 110007 India
| | - Ravins Dohare
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025 India
| | - Indrakant Kumar Singh
- Molecular Biology Research Lab, Department of Zoology, Deshbandhu College, University of Delhi, Kalkaji, New Delhi, 110019 India
- DBC i4 Center, Deshbandhu College, University of Delhi, Kalkaji, New Delhi, 110019 India
| | - Mansoor Ali Syed
- Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, 110025 India
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Han Y, Wang Y, Zhang C, Li Y, Guo J, Tian C. Metastasis-associated lung adenocarcinoma transcript 1 induces methyl-CpG-binding domain protein 4 in mice with recurrent spontaneous abortion caused by anti-phospholipid antibody positivity. Placenta 2023; 137:38-48. [PMID: 37068447 DOI: 10.1016/j.placenta.2023.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 02/27/2023] [Accepted: 04/07/2023] [Indexed: 04/19/2023]
Abstract
INTRODUCTION Antiphospholipid syndrome is an autoimmune disease characterized by pregnancy-related morbidity, related to persistent positivity of antiphospholipid antibodies (APL). One of the characteristics of pregnancy-related morbidity in patients with antiphospholipid syndrome is recurrent spontaneous abortion (RSA). This study aimed to examine the mechanism through which metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) regulates methyl-CpG-binding domain protein 4 (MBD4) expression in APL-positive RSA. METHODS Clinical samples were subjected to microarray analysis to filter differentially expressed genes. RSA mice with APL positivity were generated, followed by adenoviral vector injection to artificially upregulate MALAT1. The effects of MALAT1 on the biological behavior of trophoblast cells were assessed. The downstream mechanism of MALAT1 was analyzed using subcellular fractionation and bioinformatics prediction, and the relationship between MALAT1 and CREB binding protein (CREBBP) or MBD4 was investigated in trophoblast cells. RESULTS MALAT1 was downregulated in APL-positive RSA patients. MALAT1 was predominantly localized in the nucleus and recruited CREBBP to mediate the MBD4 transcription. In the APL-positive RSA mice overexpressing MALAT1, the expression of soluble Fms-related tyrosine kinase 1 and anticardiolipin antibody and the embryonic resorption rate were decreased, indicating that MALAT1 reduced the occurrence of RSA in mice. Moreover, MALAT1 enhanced proliferation, migration, and invasion of trophoblast cells through recruiting CREBBP to promote MBD4 expression. Silencing of CREBBP or MBD4 increased embryonic resorption rate in RSA mice overexpressing MALAT1. DISCUSSION MALAT1 suppresses APL-positive RSA by promoting MBD4 transcription through recruitment of CREBBP to the MBD4 promoter region.
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Affiliation(s)
- Yongmei Han
- College of Integrated Traditional Chinese and Western Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, 450046, Henan, PR China.
| | - Ying Wang
- Reproductive Center, Nanyang First People's Hospital, Nanyang, 473000, Henan, PR China
| | - Chenyu Zhang
- Department of Reproductive Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, Henan, PR China
| | - Yanru Li
- Department of Reproductive Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, Henan, PR China
| | - Jing Guo
- Department of Reproductive Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, Henan, PR China
| | - Chao Tian
- Department of Reproductive Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, Henan, PR China
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Zeng Z, Lan Y, Chen Y, Zuo F, Gong Y, Luo G, Peng Y, Yuan Z. LncRNA GAS5 suppresses inflammatory responses by inhibiting HMGB1 release via miR-155-5p/SIRT1 axis in sepsis. Eur J Pharmacol 2023; 942:175520. [PMID: 36693551 DOI: 10.1016/j.ejphar.2023.175520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/17/2023] [Accepted: 01/17/2023] [Indexed: 01/22/2023]
Abstract
Sepsis comprises a lethal immunologic response due to infection. Increasingly, evidence has demonstrated the important role of long non-coding RNA growth arrest-specific transcript 5 (GAS5) in the regulation of sepsis. Nevertheless, the mechanisms by which GAS5 participates in the progression of sepsis remain unclear. Our study demonstrated the role and underlying mechanism of GAS5 in regulating lipopolysaccharide (LPS)-induced inflammation. In this study, GAS5 expression was found to be markedly decreased in serum samples of sepsis patients and a sepsis mouse model, and was negatively related with HMGB1 expression. GAS5 overexpression inhibited cell inflammatory responses by decreasing HMGB1 release. Furthermore, GAS5 inhibited LPS-mediated hyperacetylation and the release of HMGB1 by increasing the expression of sirtuin1 (SIRT1). Additionally, upregulated GAS5 attenuated inflammatory responses in vitro and vivo, and the knockdown of a miR-155-5p mimic and SIRT1 rescued the effects of GAS5 upregulation. Mechanistically, GAS5 sponged miR-155-5p to upregulate SIRT1, thereby inhibiting HMGB1 acetylation and release. In conclusion, our findings indicate that GAS5 suppresses inflammatory responses by modulating the miR-155-5p/SIRT1/HMGB1 axis in sepsis, providing a novel therapeutic target for inflammation in sepsis.
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Affiliation(s)
- Zhuo Zeng
- Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yingying Lan
- Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yu Chen
- Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Fangqing Zuo
- Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yali Gong
- Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Gaoxing Luo
- Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yizhi Peng
- Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhiqiang Yuan
- Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
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Rad LM, Sadoughi MM, Nicknam A, Colagar AH, Hussen BM, Taheri M, Ghafouri-Fard S. The impact of non-coding RNAs in the pathobiology of eye disorders. Int J Biol Macromol 2023; 239:124245. [PMID: 37001772 DOI: 10.1016/j.ijbiomac.2023.124245] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 03/06/2023] [Accepted: 03/15/2023] [Indexed: 03/31/2023]
Abstract
Eye disorders are common disorders with significant effects on personal, economic, and social aspects of life. These disorders have a genetic background and are associated with dysregulation of non-coding RNAs. Three classes of these transcripts, namely long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) have established roles in the regulation of gene expression and pathoetiology of ocular disorders. H19, MEG3, BANCR, UCA1, HOTAIR, ANRIL, XIST and MIAT are among important lncRNAs in ocular disorders. CircRNAs from ZBTB44, HIPK3, circ-PSEN1, COL1A2, ZNF532 and FAM158A loci have also been found to affect pathoetiology of ocular disorders. Both lncRNAs and circRNAs can serve as molecular sponges for miRNAs. In this review, we searched PubMed and Google Scholar databases to find the research articles summarizing the impact of non-coding RNAs in ocular disorders. The results of these studies would help in identification of suitable targets for treatment of ocular disorders.
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Ding F, Zhu J, Hu Y. Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux. Acta Cir Bras 2023; 38:e380323. [PMID: 36888755 PMCID: PMC10037555 DOI: 10.1590/acb380323] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 01/06/2023] [Indexed: 03/08/2023] Open
Abstract
PURPOSE Sepsis is characterized by an acute inflammatory response to infection, often with multiple organ failures, especially severe lung injury. This study was implemented to probe circular RNA (circRNA) protein tyrosine kinase 2 (circPTK2)-associated regulatory mechanisms in septic acute lung injury (ALI). METHODS A cecal ligation and puncture-based mouse model and an lipopolysaccharides (LPS)-based alveolar type II cell (RLE-6TN) model were generated to mimic sepsis. In the two models, inflammation- and pyroptosis-related genes were measured. RESULTS The degree of lung injury in mice was analyzed by hematoxylin and eosin (H&E) staining and the apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. In addition, pyroptosis and toxicity were detected in cells. Finally, the binding relationship between circPTK2, miR-766, and eukaryotic initiation factor 5A (eIF5A) was detected. Data indicated that circPTK2 and eIF5A were up-regulated and miR-766 was down-regulated in LPS-treated RLE-6TN cells and lung tissue of septic mice. Lung injury in septic mice was ameliorated after inhibition of circPTK2. CONCLUSIONS It was confirmed in the cell model that knockdown of circPTK2 effectively ameliorated LPS-induced ATP efflux, pyroptosis, and inflammation. Mechanistically, circPTK2 mediated eIF5A expression by competitively adsorbing miR-766. Taken together, circPTK2/miR-766/eIF5A axis ameliorates septic ALI, developing a novel therapeutic target for the disease.
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Affiliation(s)
- FuYan Ding
- Zhengzhou University - Central China Fuwai Hospital - Department of Adult Cardiovascular Surgical Intensive Care Unit - Zhengzhou (Henan), China
| | - JiaLu Zhu
- Zhengzhou University - Central China Fuwai Hospital - Department of Adult Cardiovascular Surgical Intensive Care Unit - Zhengzhou (Henan), China
| | - YanLei Hu
- Zhengzhou University - Central China Fuwai Hospital - Department of Adult Cardiovascular Surgical Intensive Care Unit - Zhengzhou (Henan), China
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Yang D, Zhao D, Ji J, Wang C, Liu N, Bao X, Liu X, Jiang S, Zhang Q, Tang L. CircRNA_0075723 protects against pneumonia-induced sepsis through inhibiting macrophage pyroptosis by sponging miR-155-5p and regulating SHIP1 expression. Front Immunol 2023; 14:1095457. [PMID: 36923408 PMCID: PMC10008927 DOI: 10.3389/fimmu.2023.1095457] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 02/16/2023] [Indexed: 03/01/2023] Open
Abstract
Introduction Circular RNAs (circRNAs) have been linked to regulate macrophage polarization and subsequent inflammation in sepsis. However, the underlying mechanism and the function of circRNAs in macrophage pyroptosis in pneumonia-induced sepsis are still unknown. Methods In this study, we screened the differentially expressed circRNAs among the healthy individuals, pneumonia patients without sepsis and pneumonia-induced sepsis patients in the plasma by RNA sequencing (RNA-seq). Then we evaluated macrophage pyroptosis in sepsis patients and in vitro LPS/nigericin activated THP-1 cells. The lentiviral recombinant vector for circ_0075723 overexpression (OE-circ_0075723) and circ_0075723 silence (sh-circ_0075723) were constructed and transfected into THP-1 cells to explore the potential mechanism of circ_0075723 involved in LPS/nigericin induced macrophage pyroptosis. Results We found circ_0075723, a novel circRNA that was significantly downregulated in pneumonia-induced sepsis patients compared to pneumonia patients without sepsis and healthy individuals. Meanwhile, pneumonia-induced sepsis patients exhibited activation of NLRP3 inflammasome and production of the pyroptosis-associated pro-inflammatory cytokines IL-1β and IL-18. circ_0075723 inhibited macrophage pyroptosis via sponging miR-155-5p which promoted SHIP1 expression directly. Besides, we found that circ_0075723 in macrophages promoted VE-cadherin expression in endothelial cells through inhibiting the release of NLRP3 inflammasome-related cytokines, IL-1β and IL-18, and protects endothelial cell integrity. Discussion Our findings propose a unique approach wherein circ_0075723 suppresses macrophage pyroptosis and inflammation in pneumonia-induced sepsis via sponging with miR-155-5p and promoting SHIP1 expression. These findings indicate that circRNAs could be used as possible potential diagnostic and therapeutic targets for pneumonia-induced sepsis.
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Affiliation(s)
- Dianyin Yang
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Medical School, Tongji University, Shanghai, China
| | - Dongyang Zhao
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Medical School, Tongji University, Shanghai, China
| | - Jinlu Ji
- Medical School, Tongji University, Shanghai, China
| | - Chunxue Wang
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Medical School, Tongji University, Shanghai, China
| | - Na Liu
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiaowei Bao
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Medical School, Tongji University, Shanghai, China
| | - Xiandong Liu
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Sen Jiang
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | | | - Lunxian Tang
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
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Gu J, Rao W, Huo S, Fan T, Qiu M, Zhu H, Chen D, Sheng X. MicroRNAs and long non-coding RNAs in cartilage homeostasis and osteoarthritis. Front Cell Dev Biol 2022; 10:1092776. [PMID: 36582467 PMCID: PMC9793335 DOI: 10.3389/fcell.2022.1092776] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 11/29/2022] [Indexed: 12/14/2022] Open
Abstract
During the last decade, osteoarthritis (OA) has become one of the most prevalent musculoskeletal diseases worldwide. OA is characterized by progressive loss of articular cartilage, abnormal remodeling of subchondral bone, hyperplasia of synovial cells, and growth of osteophytes, which lead to chronic pain and disability. The pathological mechanisms underlying OA initiation and progression are still poorly understood. Non-coding RNAs (ncRNAs) constitute a large portion of the transcriptome that do not encode proteins but function in numerous biological processes. Cumulating evidence has revealed a strong association between the changes in expression levels of ncRNA and the disease progression of OA. Moreover, loss- and gain-of-function studies utilizing transgenic animal models have demonstrated that ncRNAs exert vital functions in regulating cartilage homeostasis, degeneration, and regeneration, and changes in ncRNA expression can promote or decelerate the progression of OA through distinct molecular mechanisms. Recent studies highlighted the potential of ncRNAs to serve as diagnostic biomarkers, prognostic indicators, and therapeutic targets for OA. MiRNAs and lncRNAs are two major classes of ncRNAs that have been the most widely studied in cartilage tissues. In this review, we focused on miRNAs and lncRNAs and provided a comprehensive understanding of their functional roles as well as molecular mechanisms in cartilage homeostasis and OA pathogenesis.
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Affiliation(s)
- Jingliang Gu
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wu Rao
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shaochuan Huo
- Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Tianyou Fan
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Minlei Qiu
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Haixia Zhu
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Deta Chen
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaoping Sheng
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Ghafouri-Fard S, Shoorei H, Hussen BM, Poornajaf Y, Taheri M, Sharifi G. Interplay between programmed death-ligand 1 and non-coding RNAs. Front Immunol 2022; 13:982902. [PMID: 36405753 PMCID: PMC9667550 DOI: 10.3389/fimmu.2022.982902] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 10/21/2022] [Indexed: 01/25/2023] Open
Abstract
Programmed death-ligand 1 (PD-L1) is a transmembrane protein with essential roles in the suppression of adaptive immune responses. As an immune checkpoint molecule, PD-L1 can be exploited by cancer cells to evade the anti-tumor attacks initiated by the immune system. Thus, blockade of the PD1/PD-L1 axis can eliminate the suppressive signals and release the antitumor immune responses. Identification of the underlying mechanisms of modulation of the activity of the PD1/PD-L1 axis would facilitate the design of more efficacious therapeutic options and better assignment of patients for each option. Recent studies have confirmed the interactions between miRNAs/lncRNAs/circ-RNAs and the PD1/PD-L1 axis. In the current review, we give a summary of interactions between these transcripts and PD-L1 in the context of cancer. We also overview the consequences of these interactions in the determination of the response of patients to anti-cancer drugs.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Shoorei
- Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran,Department of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan, Iraq,Center of Research and Strategic Studies, Lebanese French University, Erbil, Kurdistan, Iraq
| | - Yadollah Poornajaf
- Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Mohammad Taheri
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Institute of Human Genetics, Jena University Hospital, Jena, Germany,*Correspondence: Mohammad Taheri, ; Guive Sharifi,
| | - Guive Sharifi
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran,*Correspondence: Mohammad Taheri, ; Guive Sharifi,
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27
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Yang Q, Luo Y, Lan B, Dong X, Wang Z, Ge P, Zhang G, Chen H. Fighting Fire with Fire: Exosomes and Acute Pancreatitis-Associated Acute Lung Injury. Bioengineering (Basel) 2022; 9:615. [PMID: 36354526 PMCID: PMC9687423 DOI: 10.3390/bioengineering9110615] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/18/2022] [Accepted: 10/24/2022] [Indexed: 08/30/2023] Open
Abstract
Acute pancreatitis (AP) is a prevalent clinical condition of the digestive system, with a growing frequency each year. Approximately 20% of patients suffer from severe acute pancreatitis (SAP) with local consequences and multi-organ failure, putting a significant strain on patients' health insurance. According to reports, the lungs are particularly susceptible to SAP. Acute respiratory distress syndrome, a severe type of acute lung injury (ALI), is the primary cause of mortality among AP patients. Controlling the mortality associated with SAP requires an understanding of the etiology of AP-associated ALI, the discovery of biomarkers for the early detection of ALI, and the identification of potentially effective drug treatments. Exosomes are a class of extracellular vesicles with a diameter of 30-150 nm that are actively released into tissue fluids to mediate biological functions. Exosomes are laden with bioactive cargo, such as lipids, proteins, DNA, and RNA. During the initial stages of AP, acinar cell-derived exosomes suppress forkhead box protein O1 expression, resulting in M1 macrophage polarization. Similarly, macrophage-derived exosomes activate inflammatory pathways within endothelium or epithelial cells, promoting an inflammatory cascade response. On the other hand, a part of exosome cargo performs tissue repair and anti-inflammatory actions and inhibits the cytokine storm during AP. Other reviews have detailed the function of exosomes in the development of AP, chronic pancreatitis, and autoimmune pancreatitis. The discoveries involving exosomes at the intersection of AP and acute lung injury (ALI) are reviewed here. Furthermore, we discuss the therapeutic potential of exosomes in AP and associated ALI. With the continuous improvement of technological tools, the research on exosomes has gradually shifted from basic to clinical applications. Several exosome-specific non-coding RNAs and proteins can be used as novel molecular markers to assist in the diagnosis and prognosis of AP and associated ALI.
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Affiliation(s)
- Qi Yang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
| | - Yalan Luo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Bowen Lan
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Xuanchi Dong
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Zhengjian Wang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Peng Ge
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Guixin Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
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Antonakos N, Gilbert C, Théroude C, Schrijver IT, Roger T. Modes of action and diagnostic value of miRNAs in sepsis. Front Immunol 2022; 13:951798. [PMID: 35990654 PMCID: PMC9389448 DOI: 10.3389/fimmu.2022.951798] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 07/08/2022] [Indexed: 11/13/2022] Open
Abstract
Sepsis is a clinical syndrome defined as a dysregulated host response to infection resulting in life-threatening organ dysfunction. Sepsis is a major public health concern associated with one in five deaths worldwide. Sepsis is characterized by unbalanced inflammation and profound and sustained immunosuppression, increasing patient susceptibility to secondary infections and mortality. microRNAs (miRNAs) play a central role in the control of many biological processes, and deregulation of their expression has been linked to the development of oncological, cardiovascular, neurodegenerative and metabolic diseases. In this review, we discuss the role of miRNAs in sepsis pathophysiology. Overall, miRNAs are seen as promising biomarkers, and it has been proposed to develop miRNA-based therapies for sepsis. Yet, the picture is not so straightforward because of the versatile and dynamic features of miRNAs. Clearly, more research is needed to clarify the expression and role of miRNAs in sepsis, and to promote the use of miRNAs for sepsis management.
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Affiliation(s)
| | | | | | | | - Thierry Roger
- Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Epalinges, Switzerland
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Wen R, Liu YP, Tong XX, Zhang TN, Yang N. Molecular mechanisms and functions of pyroptosis in sepsis and sepsis-associated organ dysfunction. Front Cell Infect Microbiol 2022; 12:962139. [PMID: 35967871 PMCID: PMC9372372 DOI: 10.3389/fcimb.2022.962139] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/06/2022] [Indexed: 12/17/2022] Open
Abstract
Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of death in intensive care units. The development of sepsis-associated organ dysfunction (SAOD) poses a threat to the survival of patients with sepsis. Unfortunately, the pathogenesis of sepsis and SAOD is complicated, multifactorial, and has not been completely clarified. Recently, numerous studies have demonstrated that pyroptosis, which is characterized by inflammasome and caspase activation and cell membrane pore formation, is involved in sepsis. Unlike apoptosis, pyroptosis is a pro-inflammatory form of programmed cell death that participates in the regulation of immunity and inflammation. Related studies have shown that in sepsis, moderate pyroptosis promotes the clearance of pathogens, whereas the excessive activation of pyroptosis leads to host immune response disorders and SAOD. Additionally, transcription factors, non-coding RNAs, epigenetic modifications and post-translational modifications can directly or indirectly regulate pyroptosis-related molecules. Pyroptosis also interacts with autophagy, apoptosis, NETosis, and necroptosis. This review summarizes the roles and regulatory mechanisms of pyroptosis in sepsis and SAOD. As our understanding of the functions of pyroptosis improves, the development of new diagnostic biomarkers and targeted therapies associated with pyroptosis to improve clinical outcomes appears promising in the future.
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Affiliation(s)
| | | | | | | | - Ni Yang
- *Correspondence: Tie-Ning Zhang, ; Ni Yang,
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30
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Non-Coding RNA Networks as Potential Novel Biomarker and Therapeutic Target for Sepsis and Sepsis-Related Multi-Organ Failure. Diagnostics (Basel) 2022; 12:diagnostics12061355. [PMID: 35741168 PMCID: PMC9222180 DOI: 10.3390/diagnostics12061355] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/27/2022] [Accepted: 05/28/2022] [Indexed: 02/04/2023] Open
Abstract
According to “Sepsis-3” consensus, sepsis is a life-threatening clinical syndrome caused by a dysregulated inflammatory host response to infection. A rapid identification of sepsis is mandatory, as the extent of the organ damage triggered by both the pathogen itself and the host’s immune response could abruptly evolve to multiple organ failure and ultimately lead to the death of the patient. The most commonly used therapeutic strategy is to provide hemodynamic and global support to the patient and to rapidly initiate broad-spectrum empiric antibiotic therapy. To date, there is no gold standard diagnostic test that can ascertain the diagnosis of sepsis. Therefore, once sepsis is suspected, the presence of organ dysfunction can be assessed using the Sepsis-related Organ Failure Assessment (SOFA) score, although the diagnosis continues to depend primarily on clinical judgment. Clinicians can now rely on several serum biomarkers for the diagnosis of sepsis (e.g., procalcitonin), and promising new biomarkers have been evaluated, e.g., presepsin and adrenomedullin, although their clinical relevance in the hospital setting is still under discussion. Non-codingRNA, including long non-codingRNAs (lncRNAs), circularRNAs (circRNAs) and microRNAs (miRNAs), take part in a complex chain of events playing a pivotal role in several important regulatory processes in humans. In this narrative review we summarize and then analyze the function of circRNAs-miRNA-mRNA networks as putative novel biomarkers and therapeutic targets for sepsis, focusing only on data collected in clinical settings in humans.
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31
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Yang Y, Li M, Ma Y, Ye W, Si Y, Zheng X, Liu H, Cheng L, Zhang L, Zhang H, Zhang X, Lei Y, Shen L, Zhang F, Ma H. LncRNA NEAT1 Potentiates SREBP2 Activity to Promote Inflammatory Macrophage Activation and Limit Hantaan Virus Propagation. Front Microbiol 2022; 13:849020. [PMID: 35495674 PMCID: PMC9044491 DOI: 10.3389/fmicb.2022.849020] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 03/10/2022] [Indexed: 11/17/2022] Open
Abstract
As the global prototypical zoonotic hantavirus, Hantaan virus (HTNV) is prevalent in Asia and is the leading causative agent of severe hemorrhagic fever with renal syndrome (HFRS), which has profound morbidity and mortality. Macrophages are crucial components of the host innate immune system and serve as the first line of defense against HTNV infection. Previous studies indicated that the viral replication efficiency in macrophages determines hantavirus pathogenicity, but it remains unknown which factor manipulates the macrophage activation pattern and the virus-host interaction process. Here, we performed the transcriptomic analysis of HTNV-infected mouse bone marrow-derived macrophages and identified the long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1), especially the isoform NEAT1-2, as one of the lncRNAs that is differentially expressed at the early phase. Based on coculture experiments, we revealed that silencing NEAT1-2 hinders inflammatory macrophage activation and facilitates HTNV propagation, while enhancing NEAT1-2 transcription effectively restrains viral replication. Furthermore, sterol response element binding factor-2 (SREBP2), which controls the cholesterol metabolism process, was found to stimulate macrophages by promoting the production of multiple inflammatory cytokines upon HTNV infection. NEAT1-2 could potentiate SREBP2 activity by upregulating Srebf1 expression and interacting with SREBP2, thus stimulating inflammatory macrophages and limiting HTNV propagation. More importantly, we demonstrated that the NEAT1-2 expression level in patient monocytes was negatively correlated with viral load and HFRS disease progression. Our results identified a function and mechanism of action for the lncRNA NEAT1 in heightening SREBP2-mediated macrophage activation to restrain hantaviral propagation and revealed the association of NEAT1 with HFRS severity.
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Affiliation(s)
- Yongheng Yang
- College of Life Sciences, Northwest University, Xi'an, China.,Department of Microbiology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China
| | - Mengyun Li
- College of Life Sciences, Northwest University, Xi'an, China.,Department of Microbiology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China
| | - Yongtao Ma
- Department of Emergency, Children's Hospital of Kaifeng City, Kaifeng, China
| | - Wei Ye
- Department of Microbiology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China
| | - Yue Si
- Department of Microbiology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China
| | - Xuyang Zheng
- Department of Microbiology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China.,Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China
| | - He Liu
- Department of Microbiology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China
| | - Linfeng Cheng
- Department of Microbiology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China
| | - Liang Zhang
- Department of Microbiology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China
| | - Hui Zhang
- Department of Microbiology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China
| | - Xijing Zhang
- Department of Anesthesiology and Critical Care Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
| | - Yingfeng Lei
- Department of Microbiology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China
| | - Lixin Shen
- College of Life Sciences, Northwest University, Xi'an, China
| | - Fanglin Zhang
- Department of Microbiology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China
| | - Hongwei Ma
- Department of Microbiology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China.,Department of Anesthesiology and Critical Care Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
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32
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Li K, Liu F. Analysis of competing endogenous RNA (ceRNA) crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol 2022; 12:1468-1479. [PMID: 35385217 PMCID: PMC10084371 DOI: 10.1002/alr.23008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/11/2022] [Accepted: 04/01/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most common chronic inflammatory diseases, and has various phenotypes. Although its pathophysiology remains obscure, evidence has shown that dysregulation of noncoding RNAs (ncRNAs) is associated with CRSwNP. ncRNAs in the cytoplasm can act as competing endogenous RNAs (ceRNAs), which are involved in many inflammatory processes. However, the ceRNA crosstalk in CRSwNP is still unclear METHODS: We investigated expression profiles of messenger RNA (mRNA), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) in eosinophilic CRSwNP and constructed a global triple ceRNA network. RESULTS As a result, 964 differentially expressed mRNAs (DEmRs), 207 differentially expressed miRNAs (DEmiRs), and 15 differentially expressed lncRNAs (DElncRs) were identified, and a ceRNA network containing 598 miRNA-mRNA pairs and 70 lncRNA-miRNA pairs was finally constructed. Gene set enrichment analysis (GSEA) results indicated these DEmRs were mainly enriched in "cytokine-cytokine receptor interaction," "salivary secretion," "hematopoietic cell lineage," and "chemokine signaling pathway." Moreover, we also predicted the subcellular localization of the DElncRs identified in the network via bioinformatics approaches CONCLUSION: In summary, the present study provided the first comprehensive assessment of the ceRNA crosstalk in eosinophilic CRSwNP. These findings will be of interest to the understanding of the potential pathophysiology of this disease.
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Affiliation(s)
- Ke Li
- Department of Blood TransfusionTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Fang‐Fang Liu
- Department of PathologyThe Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
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Upregulation of circ_0059961 suppresses cholangiocarcinoma development by modulating miR-629-5p/SFRP2 axis. Pathol Res Pract 2022; 234:153901. [DOI: 10.1016/j.prp.2022.153901] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 04/03/2022] [Accepted: 04/15/2022] [Indexed: 12/25/2022]
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Wang Y, Xu H, Chen N, Yang J, Zhou H. LncRNA: A Potential Target for Host-Directed Therapy of Candida Infection. Pharmaceutics 2022; 14:pharmaceutics14030621. [PMID: 35335994 PMCID: PMC8954347 DOI: 10.3390/pharmaceutics14030621] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 02/25/2022] [Accepted: 03/09/2022] [Indexed: 02/01/2023] Open
Abstract
Despite various drugs work against Candida, candidiasis represents clinical management challenges worldwide due to the rising incidence and recurrence rate, as well as epidemics, of new drug-resistant pathogens. Recent insights into interactions between Candida and hosts contribute to exploring novel therapeutic strategies, termed host-directed therapies (HDTs). HDTs are viable adjuncts with good efficacy for the existing standard antifungal regimens. However, HDTs induce other response unintendedly, thus requiring molecular targets with highly specificity. Long noncoding RNAs (lncRNAs) with highly specific expression patterns could affect biological processes, including the immune response. Herein, this review will summarize recent advances of HDTs based on the Candida–host interaction. Especially, the findings and application strategies of lncRNAs related to the host response are emphasized. We propose it is feasible to target lncRNAs to modulate the host defense during Candida infection, which provides a new perspective in identifying options of HDTs for candidiasis.
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