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Luo Y, Ren Q, He J, Wu M. miR-126-3p Serves as a Biomarker for Hepatitis B Virus-Associated Chronic Acute Liver Failure and Regulates Inflammation by Regulating ERRFI1. J Biochem Mol Toxicol 2025; 39:e70252. [PMID: 40227026 DOI: 10.1002/jbt.70252] [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: 11/26/2024] [Revised: 02/14/2025] [Accepted: 03/31/2025] [Indexed: 04/15/2025]
Abstract
Hepatitis B virus-associated chronic acute liver failure (HBV-ACLF) is the leading cause of ACLF, affecting approximately 90% of patients with ACLF. The objective of this study was to investigate the clinical relevance of miR-126-3p on HBV-ACLF as well as the regulatory impact of ERRFI1 and miR-126-3p on the inflammatory response caused by ACLF via in vitro experimental methodologies. RT-qPCR was utilized to quantify the expression levels of miR-126-3p, ERRFI1, NLRP3, caspase 1, and IL-1β. The clinical function of miR-126-3p was assessed using ROC analysis or Kaplan-Meier curve. Cell proliferation was quantified via the CCK-8 assay, while the dual-luciferase reporter assay was employed to confirm the specific binding interaction between miR-126-3p and ERRFI1. In patients with HBV-ACLF, a significant downregulation of miR-126-3p expression was observed; The level of miR-126-3p served as a prognostic indicator for the progression of HBV-ACLF, with reduced expression being associated with an unfavorable clinical outcome. In addition, miR-126-3p was found to modulate LPS-induced cell proliferation, and inflammation in THLE-2 cells through the regulation of ERRFI1 expression. Therefore, miR-126-3p might serve as a biomarker for HBV-ACLF.
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Affiliation(s)
- Yiping Luo
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Qiuping Ren
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Jun He
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Menghang Wu
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
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2
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Sartorius K, Wang Y, Sartorius B, Antwi SO, Li X, Chuturgoon A, Yu C, Lu Y, Wang Y. The interactive role of microRNA and other non-coding RNA in hepatitis B (HBV) associated fibrogenesis. Funct Integr Genomics 2025; 25:24. [PMID: 39847120 DOI: 10.1007/s10142-024-01519-4] [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: 09/30/2024] [Revised: 11/27/2024] [Accepted: 12/27/2024] [Indexed: 01/24/2025]
Abstract
One of the outstanding features of chronic hepatitis B infection (CHB) is its strong association with liver fibrosis. CHB induced inflammation and injury trigger multiple biochemical and physical changes that include the promotion of a wide range of cytokines, chemokines and growth factors that activate hepatic stellate cells (HSCs) CHB induced activation of hepatic stellate cells (HSCs) is regarded as a central event in fibrogenesis to directly promote the synthesis of myofibroblasts and the expression of a range of materials to repair injured liver tissue. Fibrogenesis is modulated by the mainstream epigenetic machinery, as well as by non-coding RNA (ncRNA) that are often referred to as an ancillary epigenetic response to fine tune gene expression. Although extensive research has explained the regulatory role of ncRNA in liver fibrogenesis, most of this research relates to non-CHB etiologies. This review paper outlines the complex interactive regulatory role of microRNA (miRNA) and their interaction with long non-coding RNA (lncRNA), circular RNA (circRNA) and the mainstream epigenetic machinery in CHB induced liver fibrosis. The paper also illustrates some of the difficulties involved in translating candidate ncRNA into approved drugs or diagnostic tools. In conclusion, the important regulatory role of ncRNA in CHB induced liver fibrosis warrants further investigation to exploit their undoubted potential as diagnostic and therapeutic agents.
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Affiliation(s)
- Kurt Sartorius
- Faculty of Commerce, Law and Management, University of the Witwatersrand, Johannesburg, South Africa.
- Africa Hepatobiliarypancreato Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, AL, USA.
| | - Yanglong Wang
- Department of General Surgery, Xinyi People's Hospital, Xinyi, Jiangsu, China
| | - Benn Sartorius
- School of Public Health, University of Queensland, Brisbane, Australia
| | - Samuel O Antwi
- Africa Hepatobiliarypancreato Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, AL, USA
- Division of Epidemiology Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, AL, USA
| | - Xiaodong Li
- Africa Hepatobiliarypancreato Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, AL, USA
| | - Anil Chuturgoon
- School of Laboratory Medicine and Molecular Sciences, UKZN, Durban, South Africa
| | - Chongyuan Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yunjie Lu
- Africa Hepatobiliarypancreato Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, AL, USA.
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
| | - Yu Wang
- Department of Hepatobiliary Surgery, Jintan Affiliated Hospital of Jiangsu University, 213200, Changzhou, Jiangsu, China.
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da Silva LL, Leon LAA, da Cruz Moreira O, da Costa Nunes Pimentel Coelho WL, da Costa VD, Ivantes CAP, Pollo-Flores P, Lewis-Ximenez LL, de Paula VS, Villar LM. Serum microRNA 143 and 223 Gene Expression Profiles as Potential Biomarkers in Individuals with Hepatitis and COVID-19. Viruses 2024; 16:1734. [PMID: 39599849 PMCID: PMC11598994 DOI: 10.3390/v16111734] [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: 09/28/2024] [Revised: 10/25/2024] [Accepted: 10/28/2024] [Indexed: 11/29/2024] Open
Abstract
MicroRNAs (miRNAs) can act as biomarkers and descriptors of the association between infections and other diseases, such as hepatitis and COVID-19. This study aims to investigate the role of miRNA serum expression according to laboratory data concerning hepatitis and COVID-19. Seventy individuals recruited in Southern and Southeastern Brazil donated serum samples and were divided into four groups: (i) 20 negative subjects, (ii) 20 presenting hepatitis, (iii) 19 with COVID-19 and (iv) 11 with hepatitis and COVID-19. Three miRNAs (miR-122, miR-143 and miR-223) were evaluated using real-time PCR. Hematological and biochemical markers were also analyzed. MiR-143 and miR-223 were downregulated among the hepatitis/COVID-19 group (p < 0.05). A positive correlation was observed between miR-223 and lymphocytes. There was a negative correlation between alanine transaminase (ALT) and aspartate transaminase (AST) for miR-143 and miR-223 and gamma-glutamyl transferase (GGT), alkaline phosphatase (AP) and neutrophil/lymphocyte ratio (NLR) only for miR-223 (p < 0.05). For hepatic fibrosis (FIB-4), miR-122 and miR-143 had a greater association and miR-223 was more associated with a history of vaccination against COVID-19. MicroRNAs 143 and 223 could be useful as biomarkers for hepatitis coinfection with COVID-19.
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Affiliation(s)
- Lucas Lima da Silva
- National Reference Laboratory for Viral Hepatitis, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (V.D.d.C.); (L.L.L.-X.)
| | - Luciane Almeida Amado Leon
- Technological Development Laboratory, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (L.A.A.L.); (W.L.d.C.N.P.C.)
| | - Otacílio da Cruz Moreira
- Molecular Virology and Parasitology Laboratory, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (O.d.C.M.); (V.S.d.P.)
| | | | - Vanessa Duarte da Costa
- National Reference Laboratory for Viral Hepatitis, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (V.D.d.C.); (L.L.L.-X.)
| | | | - Priscila Pollo-Flores
- Department of Clinical Medicine, Fluminense Federal University, Niterói 24220-000, RJ, Brazil;
| | - Lia Laura Lewis-Ximenez
- National Reference Laboratory for Viral Hepatitis, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (V.D.d.C.); (L.L.L.-X.)
| | - Vanessa Salete de Paula
- Molecular Virology and Parasitology Laboratory, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (O.d.C.M.); (V.S.d.P.)
| | - Livia Melo Villar
- National Reference Laboratory for Viral Hepatitis, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (V.D.d.C.); (L.L.L.-X.)
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Deng H, Zhong Y, Zhao J, Li X, Luo G, Li H. Serum exosomes from hepatitis B virus-infected patients inhibit glycolysis in Sertoli cells via miR-122-5p/ALDOA axis. Reprod Biol 2024; 24:100845. [PMID: 38159424 DOI: 10.1016/j.repbio.2023.100845] [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: 09/13/2023] [Revised: 11/22/2023] [Accepted: 12/14/2023] [Indexed: 01/03/2024]
Abstract
Hepatitis B virus (HBV) infection is associated with male infertility. The mechanism includes an increase in chromosomal instability in sperm, which has an adverse effect on sperm viability and function. Sertoli cells (SCs) are vital in spermatogenesis because they use glycolysis to provide energy to germ cells and themselves. HBV infection impairs sperm function. However, whether HBV infection disrupts energy metabolism in SCs remains unclear. This study aimed to determine the role of serum exosomes of HBV-infected patients in SC viability and glycolysis. Serum exosomes were obtained from 30 patients with (HBV+_exo) or without (HBV-_exo) HBV infection using high-speed centrifugation and identified by transmission electron microscopy and western blot analysis. Cell viability is determined by CCK-8 assay. Glycolysis is determined by detecting extracellular acidification rate and ATP levels. miR-122-5p expression levels are detected by quantitative RT-PCR, and a dual-luciferase gene reporter assay confirms the downstream target gene of miR-122-5p. Protein expression is determined by western blot analysis. The results show that HBV+ _exo inhibited cell viability, extracellular acidification rate, and ATP production of SCs. miR-122-5p is highly expressed in HBV+ _exo compared with that in HBV-_exo. Furthermore, HBV+ _exo is efficiently taken up by SCs, whereas miR-122-5p is efficiently transported to SCs. miR-122-5p overexpression downregulates ALDOA expression and inhibits SC viability and glycolysis. However, ALDOA overexpression reverses the effects of miR-122-5p and HBV+ _exo on SC viability and glycolysis. HBV+ _exo may deliver miR-122-5p to target ALDOA and inhibit SC viability and glycolysis, thus providing new therapeutic ideas for treating HBV-associated male infertility.
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Affiliation(s)
- Hao Deng
- Assisted Reproductive Technology Center, Foshan Women and Children Hospital, Foshan 528000, China
| | - Yucheng Zhong
- Assisted Reproductive Technology Center, Foshan Women and Children Hospital, Foshan 528000, China
| | - Jun Zhao
- Assisted Reproductive Technology Center, Foshan Women and Children Hospital, Foshan 528000, China
| | - Xiaohang Li
- Assisted Reproductive Technology Center, Foshan Women and Children Hospital, Foshan 528000, China
| | - Guoqun Luo
- Assisted Reproductive Technology Center, Foshan Women and Children Hospital, Foshan 528000, China.
| | - Huan Li
- Assisted Reproductive Technology Center, Foshan Women and Children Hospital, Foshan 528000, China.
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5
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Sartorius K, Sartorius B, Winkler C, Chuturgoon A, Shen TW, Zhao Y, An P. Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study. Int J Mol Sci 2024; 25:975. [PMID: 38256049 PMCID: PMC10815595 DOI: 10.3390/ijms25020975] [Citation(s) in RCA: 5] [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: 11/07/2023] [Revised: 12/28/2023] [Accepted: 12/29/2023] [Indexed: 01/24/2024] Open
Abstract
The incidence and mortality of hepatocellular carcinoma (HCC) in Sub-Saharan Africa is projected to increase sharply by 2040 against a backdrop of limited diagnostic and therapeutic options. Two large South African-based case control studies have developed a serum-based miRNome for Hepatitis B-associated hepatocellular carcinoma (HBV-HCC), as well as identifying their gene targets and pathways. Using a combination of RNA sequencing, differential analysis and filters including a unique molecular index count (UMI) ≥ 10 and log fold change (LFC) range > 2: <-0.5 (p < 0.05), 91 dysregulated miRNAs were characterized including 30 that were upregulated and 61 were downregulated. KEGG analysis, a literature review and other bioinformatic tools identified the targeted genes and HBV-HCC pathways of the top 10 most dysregulated miRNAs. The results, which are based on differentiating miRNA expression of cases versus controls, also develop a serum-based miRNA diagnostic panel that indicates 95.9% sensitivity, 91.0% specificity and a Youden Index of 0.869. In conclusion, the results develop a comprehensive African HBV-HCC miRNome that potentially can contribute to RNA-based diagnostic and therapeutic options.
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Affiliation(s)
- Kurt Sartorius
- Faculty of Commerce, Law and Management, University of the Witwatersrand, Johannesburg 2001, South Africa
- School of Laboratory Medicine and Molecular Sciences, University of Kwazulu-Natal, Durban 4041, South Africa;
- Africa Hepatopancreatobiliary Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, FL 32224, USA
| | - Benn Sartorius
- School of Public Health, University of Queensland, Brisbane, QLD 4102, Australia
| | - Cheryl Winkler
- Centre for Cancer Research, Basic Research Laboratory, National Cancer Institute, Frederick Natifol Laboratory for Cancer Research, National Institute of Health, Frederick, MD 21701, USA
| | - Anil Chuturgoon
- School of Laboratory Medicine and Molecular Sciences, University of Kwazulu-Natal, Durban 4041, South Africa;
| | - Tsai-Wei Shen
- CCR-SF Bioinformatics Group, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA
| | - Yongmei Zhao
- CCR-SF Bioinformatics Group, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA
| | - Ping An
- Centre for Cancer Research, Basic Research Laboratory, National Cancer Institute, Frederick Natifol Laboratory for Cancer Research, National Institute of Health, Frederick, MD 21701, USA
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6
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Mokhtari F, Kaboosi H, Mohebbi SR, Asadzadeh Aghdaei H, Zali MR. Circulating Plasma miR-122 and miR-583 Levels Are Involved in Chronic Hepatitis B Virus Pathogenesis and Serve As Novel Diagnostic Biomarkers. Genet Test Mol Biomarkers 2023; 27:232-238. [PMID: 37643324 DOI: 10.1089/gtmb.2023.0013] [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] [Indexed: 08/31/2023] Open
Abstract
Background: MicroRNAs regulate many biological processes and are involved in the pathogenesis of many diseases including chronic hepatitis B (CHB). Moreover, besides investigation of their roles in hepatitis B virus (HBV) infection, a noninvasive, sensitive, and specific biomarker is essential in the diagnosis of liver diseases. This study was designed to evaluate the role of miR-122, miR-583, and miR-24 in the pathogenesis of CHB both in active chronic hepatitis (ACH) patients and in inactive carriers (IC). Materials and Methods: Plasma samples and all relevant clinical features were collected from 43 patients with CHB (28 ACH and 15 IC) and 43 healthy controls. Quantitative real-time PCR was performed to detect the plasma levels of miR-122, miR-583, and miR-24. Results: Results show miR-122 (p = 0.0001) and miR-583 (p = 0.006) but not miR-24 (p = 0.65) were upregulated in patients with CHB versus the control group. Interestingly, there was a significant increase in the plasma expression of miR-583 in IC versus ACH. Moreover, receiver operating characteristic curve analysis determined plasma levels of miR-122 (area under the ROC curve [AUC] = 0.89, p < 0.0001, sensitivity: 100%, specificity: 62.5%) and miR-583 (AUC = 0.71, p = 0.0007, sensitivity: 90%, specificity: 47.62%) as sensitive biomarkers to discriminate CHB patients from controls. Conclusion: Our data showed an increase in the plasma levels of miR-583 in IC versus ACH patients. Moreover, we demonstrated that miR-122 and miR-583 may serve as potential biomarkers for CHB diagnosis and activity.
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Affiliation(s)
- Fedra Mokhtari
- Department of Microbiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
| | - Hami Kaboosi
- Department of Microbiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
| | - Seyed Reza Mohebbi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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7
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Schofield AL, Brown JP, Brown J, Wilczynska A, Bell C, Glaab WE, Hackl M, Howell L, Lee S, Dear JW, Remes M, Reeves P, Zhang E, Allmer J, Norris A, Falciani F, Takeshita LY, Seyed Forootan S, Sutton R, Park BK, Goldring C. Systems analysis of miRNA biomarkers to inform drug safety. Arch Toxicol 2021; 95:3475-3495. [PMID: 34510227 PMCID: PMC8492583 DOI: 10.1007/s00204-021-03150-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023]
Abstract
microRNAs (miRNAs or miRs) are short non-coding RNA molecules which have been shown to be dysregulated and released into the extracellular milieu as a result of many drug and non-drug-induced pathologies in different organ systems. Consequently, circulating miRs have been proposed as useful biomarkers of many disease states, including drug-induced tissue injury. miRs have shown potential to support or even replace the existing traditional biomarkers of drug-induced toxicity in terms of sensitivity and specificity, and there is some evidence for their improved diagnostic and prognostic value. However, several pre-analytical and analytical challenges, mainly associated with assay standardization, require solutions before circulating miRs can be successfully translated into the clinic. This review will consider the value and potential for the use of circulating miRs in drug-safety assessment and describe a systems approach to the analysis of the miRNAome in the discovery setting, as well as highlighting standardization issues that at this stage prevent their clinical use as biomarkers. Highlighting these challenges will hopefully drive future research into finding appropriate solutions, and eventually circulating miRs may be translated to the clinic where their undoubted biomarker potential can be used to benefit patients in rapid, easy to use, point-of-care test systems.
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Affiliation(s)
- Amy L Schofield
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool, L69 3GE, UK
| | - Joseph P Brown
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool, L69 3GE, UK
| | - Jack Brown
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool, L69 3GE, UK
| | - Ania Wilczynska
- bit.bio, Babraham Research Campus, The Dorothy Hodgkin Building, Cambridge, CB22 3FH, UK
| | - Catherine Bell
- CVRM Safety, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden
| | - Warren E Glaab
- Merck & Co., Inc, 770 Sumneytown Pike, West Point, PA, 19486, USA
| | | | - Lawrence Howell
- GlaxoSmithKline (GSK), Stevenage, Greater Cambridge Area, UK
| | - Stephen Lee
- ABHI, 1 Duchess St, 4th Floor, Suite 2, London, W1W 6AN, UK
| | - James W Dear
- Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Mika Remes
- Genomics EMEA, QIAGEN Aarhus, Prismet, Silkeborgvej 2, 8000, Aarhus C, Denmark
| | - Paul Reeves
- Arcis Biotechnology Limited, Suite S07, Techspace One, Sci-tech Daresbury, Keckwick Lane, Daresbury, Warrington, WA4 4AB, UK
| | - Eunice Zhang
- Wolfson Centre for Personalised Medicine, Department of Pharmacology and Therapeutics, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK
| | - Jens Allmer
- Applied Bioinformatics, Bioscience, Wageningen University and Research, Droevendaalsesteeg 4, 6708 PB, Wageningen, The Netherlands
| | - Alan Norris
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool, L69 3GE, UK
| | - Francesco Falciani
- Computational Biology Facility, MerseyBio, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK
| | - Louise Y Takeshita
- Computational Biology Facility, MerseyBio, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK
| | - Shiva Seyed Forootan
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool, L69 3GE, UK
| | - Robert Sutton
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Biosciences Building, Crown Street, Liverpool, L69 7BE, UK
| | - B Kevin Park
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool, L69 3GE, UK
| | - Chris Goldring
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool, L69 3GE, UK.
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Loureiro D, Tout I, Narguet S, Benazzouz SM, Mansouri A, Asselah T. miRNAs as Potential Biomarkers for Viral Hepatitis B and C. Viruses 2020; 12:E1440. [PMID: 33327640 PMCID: PMC7765125 DOI: 10.3390/v12121440] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 12/07/2020] [Accepted: 12/10/2020] [Indexed: 02/06/2023] Open
Abstract
Around 257 million people are living with hepatitis B virus (HBV) chronic infection and 71 million with hepatitis C virus (HCV) chronic infection. Both HBV and HCV infections can lead to liver complications such as cirrhosis and hepatocellular carcinoma (HCC). To take care of these chronically infected patients, one strategy is to diagnose the early stage of fibrosis in order to treat them as soon as possible to decrease the risk of HCC development. microRNAs (or miRNAs) are small non-coding RNAs which regulate many cellular processes in metazoans. Their expressions were frequently modulated by up- or down-regulation during fibrosis progression. In the serum of patients with HBV chronic infection (CHB), miR-122 and miR-185 expressions are increased, while miR-29, -143, -21 and miR-223 expressions are decreased during fibrosis progression. In the serum of patients with HCV chronic infection (CHC), miR-143 and miR-223 expressions are increased, while miR-122 expression is decreased during fibrosis progression. This review aims to summarize current knowledge of principal miRNAs modulation involved in fibrosis progression during chronic hepatitis B/C infections. Furthermore, we also discuss the potential use of miRNAs as non-invasive biomarkers to diagnose fibrosis with the intention of prioritizing patients with advanced fibrosis for treatment and surveillance.
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Affiliation(s)
| | | | | | | | | | - Tarik Asselah
- Department of Hepatology, Université de Paris, CRI, INSERM UMR 1149, AP-HP Hôpital Beaujon, 92110 Clichy, France; (D.L.); (I.T.); (S.N.); (S.M.B.); (A.M.)
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9
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Xue H, Li H, Ju LL, Han XD, Cheng TC, Luo X, Chen L, Shao JG, She YJ, Bian ZL. Mucosal-associated invariant T cells in hepatitis B virus-related liver failure. World J Gastroenterol 2020; 26:4703-4717. [PMID: 32884227 PMCID: PMC7445862 DOI: 10.3748/wjg.v26.i31.4703] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 05/21/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver failure has high mortality and poor prognosis, and establishing new reliable markers for predicting its prognosis is necessary. Mucosal-associated invariant T (MAIT) cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease, and their potential role in liver failure remains unclear.
AIM To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus (HBV)-related liver failure.
METHODS We recruited 55 patients with HBV-related liver failure, 48 patients with chronic hepatitis B and 40 healthy controls (HCs) from Nantong Third People’s Hospital Affiliated to Nantong University. Peripheral blood mononuclear cells were isolated, and the percentage and number of circulating MAIT cells were detected by flow cytometry. Plasma levels of interleukin (IL)-7, IL-12p70, IL-18 and interferon-α were measured by Luminex assay.
RESULTS Circulating MAIT cells were significantly decreased in HBV-related liver failure patients (percentage: 2.00 ± 1.22 vs 5.19 ± 1.27%, P < 0.0001; number: 5.47 ± 4.93 vs 84.43 ± 19.59, P < 0.0001) compared with HCs. More importantly, there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure. Circulating MAIT cells partially recovered after disease improvement, both in percentage (4.01 ± 1.21 vs 2.04 ± 0.95%, P < 0.0001) and in cell count (17.24 ± 8.56 vs 7.41 ± 4.99, P < 0.0001). The proportion (2.29 ± 1.01 vs 1.58 ± 1.38%, P < 0.05) and number (7.30 ± 5.70 vs 2.94 ± 1.47, P < 0.001) of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group, and the Kaplan–Meier curve showed that lower expression of circulating MAIT cells (both percentage and cell count) predicted poor overall survival (P < 0.01). Also, the levels of IL-12 (20.26 ± 5.42 pg/mL vs 17.76 ± 2.79 pg/mL, P = 0.01) and IL-18 (1470.05 ± 1525.38 pg/mL vs 362.99 ± 109.64 pg/mL, P < 0.0001) were dramatically increased in HBV-related liver failure patients compared with HCs.
CONCLUSION Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker.
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Affiliation(s)
- Hong Xue
- Department of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Han Li
- Medical School of Nantong University, Nantong 226006, Jiangsu Province, China
| | - Lin-Ling Ju
- Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Xu-Dong Han
- Department of Critical Care Medicine, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Tiao-Chun Cheng
- Medical School of Nantong University, Nantong 226006, Jiangsu Province, China
| | - Xi Luo
- Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Lin Chen
- Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Jian-Guo Shao
- Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
- Department of Gastroenterology and Hepatology, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Yong-Jun She
- Department of Anesthesiology, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Zhao-Lian Bian
- Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
- Department of Gastroenterology and Hepatology, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
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10
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The Regulatory Role of MicroRNA in Hepatitis-B Virus-Associated Hepatocellular Carcinoma (HBV-HCC) Pathogenesis. Cells 2019; 8:cells8121504. [PMID: 31771261 PMCID: PMC6953055 DOI: 10.3390/cells8121504] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 11/11/2019] [Accepted: 11/12/2019] [Indexed: 02/06/2023] Open
Abstract
The incidence and mortality of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) is an intractable public health problem in developing countries that is compounded by limited early detection and therapeutic options. Despite the early promise of utilizing the regulatory role of miRNA in liver cancer, this field remains largely in the work-in-progress phase. This exploratory review paper adopts a broad focus in order to collate evidence of the regulatory role of miRNA in each stage of the HBV-HCC continuum. This includes the regulatory role of miRNA in early HBV infection, chronic inflammation, fibrosis/cirrhosis, and the onset of HCC. The paper specifically investigates HBV dysregulated miRNA that influence the expression of the host/HBV genome in HBV-HCC pathogenesis and fully acknowledges that this does not cover the full spectrum of dysregulated miRNA. The sheer number of dysregulated miRNA in each phase support a hypothesis that future therapeutic interventions will need to consider incorporating multiple miRNA panels.
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11
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Mahmoudian-Sani MR, Asgharzade S, Alghasi A, Saeedi-Boroujeni A, Adnani Sadati SJ, Moradi MT. MicroRNA-122 in patients with hepatitis B and hepatitis B virus-associated hepatocellular carcinoma. J Gastrointest Oncol 2019; 10:789-796. [PMID: 31392060 DOI: 10.21037/jgo.2019.02.14] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) infection is known as a serious problem in the domain of public health and approximately 350 million people across the world are affected with this infectious disease. As well, microRNAs are recognized as a type of small non-coding RNAs that can be widely used as a diagnostic biomarker and prognosis method of special diseases. In this respect, microRNA-122 or miR-122 can play a significant role in the pathogenesis of several hepatic diseases. Given the importance of microRNA-122 in the liver as well as its pathology, this study focused on the potential functions of microRNA-122 in pathogenesis, diagnosis, and treatment of HBV infection. In this regard, the findings of previous studies had indicated that expression of microRNA-122 in patients with HBV infection could be significantly deregulated. The results of this study were consistent with the idea that diagnosis and treatment of this infectious disease using microRNA-122 could be an efficient method.
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Affiliation(s)
- Mohammad Reza Mahmoudian-Sani
- Research Center of Thalassemia and Hemoglobinopathy, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Samira Asgharzade
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Arash Alghasi
- Research Center of Thalassemia and Hemoglobinopathy, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Seyed Jafar Adnani Sadati
- Department of Microbiology & Immunology, Faculty of Medicine, Qom University of Medical Sciences, Qom, Iran
| | - Mohammad Taghi Moradi
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
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12
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Świtlik WZ, Bielecka-Kowalska A, Karbownik MS, Kordek R, Jabłkowski M, Szemraj J. Forms of diagnostic material as sources of miRNA biomarkers in hepatocellular carcinoma: a preliminary study. Biomark Med 2019; 13:523-534. [PMID: 30854869 DOI: 10.2217/bmm-2018-0485] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Aim: To assess the diagnostic value of selected miRNAs from various material collected from hepatocellular carcinoma (HCC) patients. Patients & methods: Tissue, serum, urine and fecal samples from HCC patients and healthy individuals were screened for associated miRNAs using microarray analysis; the selected miRNAs were then validated by real time-quantitative PCR on 65 patients. Results: Serum miR-122, a combination of serum miR-155 with miR-885-5p, a combination of urinary miR-532-3p with miR-765, and fecal miR-320a displayed 100% efficiency in discriminating patients from controls. A combination of urinary miR-532-3p and miR-765 allowed patients with neoplastic grade G3 to be distinguished from those with G1 and G2. Conclusion: Additionally to serum, urine and feces also appeared to be valuable source of potential HCC noninvasive miRNA biomarkers.
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Affiliation(s)
- Weronika Zofia Świtlik
- Department of Medical Biochemistry, Medical University of Lodz, Mazowiecka Street 6/8 92-215 Lodz, Poland.,Department of Biochemistry, Faculty of Agriculture & Biology, Warsaw University of Life Sciences - SGGW, Nowoursynowska Street 159, 02-776 Warsaw, Poland
| | | | - Michał Seweryn Karbownik
- Department of Pharmacology & Toxicology, Medical University of Lodz, Zeligowskiego Street 7/9, 90-752 Lodz, Poland
| | - Radzisław Kordek
- Department of Pathology Chair of Oncology, Medical University of Lodz, Pomorska Street 251, 92-213 Lodz, Poland
| | - Maciej Jabłkowski
- Department of Infectious & Liver Diseases, Medical University of Lodz, Kniaziewicza Street 1/5, 91-347 Lodz, Poland
| | - Janusz Szemraj
- Department of Medical Biochemistry, Medical University of Lodz, Mazowiecka Street 6/8 92-215 Lodz, Poland.,BioNanoPark Laboratories, Lodz Regional Park of Science & Technologies, Dubois Street 114/116, 93-465, Lodz, Poland
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13
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Musaddaq G, Shahzad N, Ashraf MA, Arshad MI. Circulating liver-specific microRNAs as noninvasive diagnostic biomarkers of hepatic diseases in human. Biomarkers 2019; 24:103-109. [PMID: 30252499 DOI: 10.1080/1354750x.2018.1528631] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2018] [Accepted: 09/22/2018] [Indexed: 02/08/2023]
Abstract
CONTEXT Hepatitis is an endemic disease worldwide leading to chronic and debilitating cancers. The viral agents and hepatotoxic substances lead to damage of hepatocytes and release of damage associated molecules in circulation. The lack of timely and rapid diagnosis of hepatitis results in chronic disease. OBJECTIVE The present review aimed to describe regulation, release and functions of microRNAs (miR) during human liver pathology and insights into their promising use as noninvasive biomarkers of hepatitis. METHODS Comprehensive data were collected from PubMed, ScienceDirect and the Web of Science databases utilizing the keywords "biomarkers", "microRNAs" and "hepatic diseases". RESULTS The miRs are readily released in the body fluids and blood during HBV/HCV associated hepatitis as well as metabolic, alcoholic, drug induced and autoimmune hepatitis. The liver-specific microRNAs including miR-122, miR-130, miR-183, miR-196, miR-209 and miR-96 are potential indicators of liver injury (mainly via apoptosis, necrosis and necroptosis) or hepatitis with their varied expression during acute/fulminant, chronic, liver fibrosis/cirrhosis and hepato-cellular carcinoma. CONCLUSIONS The liver-specific miRs can be used as rapid and noninvasive biomarkers of hepatitis to discern different stages of hepatitis. Blocking or stimulating pathways associated with miR regulation in liver could unveil novel therapeutic strategies in the management of liver diseases. Clinical significance Liver specific microRNAs interact with cellular proteins and signaling molecules to regulate the expression of various genes controlling biological processes. The circulatory level of liver specific microRNAs is indicator of severity of HBV and HCV infections as well as prognostic and therapeutic candidates. The expression of liver specific microRNAs is strongly associated with infectious, drug-induced, hepatotoxic, nonalcoholic steatohepatitis and nonalcoholic fatty liver diseases.
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Affiliation(s)
- Ghulam Musaddaq
- a Institute of Microbiology, University of Agriculture , Faisalabad , Pakistan
| | - Naveed Shahzad
- b School of Biological Sciences (SBS), University of the Punjab , Lahore , Pakistan
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14
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The Effect of Modified Sini Decoction on Survival Rates of Patients with Hepatitis B Virus Related Acute-on-Chronic Liver Failure. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:2501847. [PMID: 30915144 PMCID: PMC6409021 DOI: 10.1155/2019/2501847] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 01/14/2019] [Accepted: 02/03/2019] [Indexed: 12/18/2022]
Abstract
Aim of the Study. To verify the effect of modified sini decoction on patients with hepatitis B virus related acute-on-chronic liver failure. Materials and Methods. A retrospective cohort study was conducted. Patients who had been treated with modified sini decoction and standard comprehensive internal medicine were assigned to an observation group, and patients who had been treated with standard comprehensive internal medicine were selected as a control group. The total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), prothrombin activity (PTA), CTP, and MELD scores were analyzed at weeks 4, 8, and 12 after treatment, respectively. Meanwhile, the 12-week survival rate was analyzed. Results. The levels of TBIL and ALT were remarkably decreased, while the levels of ALB and PTA were remarkably increased in both groups at weeks 4, 8, and 12 after treatment, respectively, but the effects in the observation group were greater (P < 0.05). The CTP and MELD scores at 8-week and 12-week were lower in the observation group than in the control group (P < 0.05). At 12 weeks, the mean survival times of the observation group and the control group were 66.7 and 45.5 d, respectively. Significant improvement of 12-week survival rate [39/62 (62.9%) versus 18/50 (36.0%), P = 0.001] was observed in the observation group after treatment. Conclusions. Modified sini decoction could protect the liver function and improve the survival rates of patients with hepatitis B virus related acute-on-chronic liver failure.
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15
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Chen EQ, Shimakami T, Fan YC, Angeli P. Acute-on-Chronic Liver Failure: From Basic Research to Clinical Applications. Can J Gastroenterol Hepatol 2018; 2018:5029789. [PMID: 30402449 PMCID: PMC6196885 DOI: 10.1155/2018/5029789] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 09/18/2018] [Indexed: 02/06/2023] Open
Affiliation(s)
- En-Qiang Chen
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Tetsuro Shimakami
- Department of Gastroenterology, Kanazawa University Graduate School of Health Medicine, Kanazawa, Japan
| | - Yu-Chen Fan
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Paolo Angeli
- Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy
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16
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Serum levels of miRNA in patients with hepatitis B virus-associated acute-on-chronic liver failure. Hepatobiliary Pancreat Dis Int 2018; 17:126-132. [PMID: 29602672 DOI: 10.1016/j.hbpd.2018.03.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 01/05/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum miRNAs in the evaluation of HBV-ACLF and to develop a model to predict the outcomes for ACLF. METHODS Serum was collected from 41 chronic hepatitis B and 55 HBV-ACLF patients in addition to 30 chronic asymptomatic HBV carriers as controls. The miRNAs expressions were measured by real-time quantitative PCR (q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed miRNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive model. RESULTS Real-time q-PCR indicated that serum miR-146a-5p, miR-122-3p and miR-328-3p levels were significantly upregulated in ACLF patients compared to chronic hepatitis B and chronic asymptomatic HBV carriers patients. In addition, multivariate regression analyses indicated that Na+, INR, gastrointestinal bleeding and miR-122-3p are all independent factors that are reliable and sensitive to the prognosis of HBV-ACLF. Therefore, we developed a new model for the prediction of HBV-ACLF disease state: Y = 0.402 × Na+ - 1.72 × INR - 4.963 × gastrointestinal bleeding (Yes = 0; No = 1)-0.278 × (miR-122-3p) + 50.449. The predictive accuracy of the model was 95.3% and the area under the receiver operating characteristic curve (AUROC) was 0.847. CONCLUSIONS Expression levels of these miRNAs (miR-146a-5p, miR-122-3p and miR-328-3p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.
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17
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Hepatic stellate cells as key target in liver fibrosis. Adv Drug Deliv Rev 2017; 121:27-42. [PMID: 28506744 DOI: 10.1016/j.addr.2017.05.007] [Citation(s) in RCA: 1019] [Impact Index Per Article: 127.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 03/21/2017] [Accepted: 05/09/2017] [Indexed: 02/06/2023]
Abstract
Progressive liver fibrosis, induced by chronic viral and metabolic disorders, leads to more than one million deaths annually via development of cirrhosis, although no antifibrotic therapy has been approved to date. Transdifferentiation (or "activation") of hepatic stellate cells is the major cellular source of matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis. Paracrine signals from injured epithelial cells, fibrotic tissue microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis, and hepatitis viral products can directly or indirectly induce stellate cell activation. Dysregulated intracellular signaling, epigenetic changes, and cellular stress response represent candidate targets to deactivate stellate cells by inducing reversion to inactivated state, cellular senescence, apoptosis, and/or clearance by immune cells. Cell type- and target-specific pharmacological intervention to therapeutically induce the deactivation will enable more effective and less toxic precision antifibrotic therapies.
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18
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Amer W, Toth C, Vassella E, Meinrath J, Koitzsch U, Arens A, Huang J, Eischeid H, Adam A, Buettner R, Scheel A, Schaefer SC, Odenthal M. Evolution analysis of heterogeneous non-small cell lung carcinoma by ultra-deep sequencing of the mitochondrial genome. Sci Rep 2017; 7:11069. [PMID: 28894165 PMCID: PMC5593826 DOI: 10.1038/s41598-017-11345-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Accepted: 08/23/2017] [Indexed: 12/20/2022] Open
Abstract
Accurate assessment of tumour heterogeneity is an important issue that influences prognosis and therapeutic decision in molecular pathology. Due to the shortage of protective histones and a limited DNA repair capacity, the mitochondrial (mt)-genome undergoes high variability during tumour development. Therefore, screening of mt-genome represents a useful molecular tool for assessing precise cell lineages and tracking tumour history. Here, we describe a highly specific and robust multiplex PCR-based ultra-deep sequencing technology for analysis of the whole mt-genome (wmt-seq) on low quality-DNA from formalin-fixed paraffin-embedded tissues. As a proof of concept, we applied the wmt-seq technology to characterize the clonal relationship of non-small cell lung cancer (NSCLC) specimens with multiple lesions (N = 43) that show either different histological subtypes (group I) or pulmonary adenosquamous carcinoma as striking examples of a mixed-histology tumour (group II). The application of wmt-seq demonstrated that most samples bear common mt-mutations in each lesion of an individual patient, indicating a single cell progeny and clonal relationship. Hereby we show the monoclonal origin of histologically heterogeneous NSCLC and demonstrate the evolutionary relation of NSCLC cases carrying heteroplasmic mt-variants.
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Affiliation(s)
- Wafa Amer
- Institute of Pathology, University Hospital of Cologne, Cologne, Germany
| | - Csaba Toth
- Institute of Pathology, University Hospital of Cologne, Cologne, Germany
| | - Erik Vassella
- Institute of Pathology, University Hospital of Bern, Bern, Switzerland
| | - Jeannine Meinrath
- Institute of Pathology, University Hospital of Cologne, Cologne, Germany
| | - Ulrike Koitzsch
- Institute of Pathology, University Hospital of Cologne, Cologne, Germany
| | | | - Jia Huang
- Institute of Pathology, University Hospital of Cologne, Cologne, Germany
| | - Hannah Eischeid
- Institute of Pathology, University Hospital of Cologne, Cologne, Germany
| | - Alexander Adam
- Institute of Pathology, University Hospital of Cologne, Cologne, Germany
| | - Reinhard Buettner
- Institute of Pathology, University Hospital of Cologne, Cologne, Germany.,Center of Integrative Oncology, University Clinic of Cologne and Bonn, Cologne, Germany.,Lung Cancer Group Cologne, University Hospital of Cologne, Cologne, Germany.,Center of Molecular Medicine of Cologne, University of Cologne, Cologne, Germany
| | - Andreas Scheel
- Institute of Pathology, University Hospital of Cologne, Cologne, Germany.,Center of Integrative Oncology, University Clinic of Cologne and Bonn, Cologne, Germany.,Lung Cancer Group Cologne, University Hospital of Cologne, Cologne, Germany
| | - Stephan C Schaefer
- Institute of Pathology, University Hospital of Cologne, Cologne, Germany.,Center of Integrative Oncology, University Clinic of Cologne and Bonn, Cologne, Germany.,Lung Cancer Group Cologne, University Hospital of Cologne, Cologne, Germany
| | - Margarete Odenthal
- Institute of Pathology, University Hospital of Cologne, Cologne, Germany. .,Center of Integrative Oncology, University Clinic of Cologne and Bonn, Cologne, Germany. .,Center of Molecular Medicine of Cologne, University of Cologne, Cologne, Germany.
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19
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Chang W. Non-coding RNAs and Berberine: A new mechanism of its anti-diabetic activities. Eur J Pharmacol 2017; 795:8-12. [DOI: 10.1016/j.ejphar.2016.11.055] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Revised: 11/29/2016] [Accepted: 11/30/2016] [Indexed: 12/20/2022]
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