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Wu J, Yang Z, Ding J, Hao S, Chen H, Jin K, Zhang C, Zheng X. Proteome-wide Mendelian randomization identifies causal plasma proteins in prostate cancer development. Hum Genomics 2025; 19:17. [PMID: 39994764 PMCID: PMC11853923 DOI: 10.1186/s40246-025-00724-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Accepted: 02/05/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND The etiology of prostate cancer remained elusive, whether plasma protein levels are associated with prostate cancer is still unknown. METHODS We have performed Mendelian randomization analyses to calculate the causal effects of plasma proteins on the risk of prostate cancer in the PRACTICAL consortium dataset using cis-protein quantitative trait loci (cis-pQTL) variants as instrumental variables for plasma proteins, and cis-expression quantitative trait locus (cis-eQTL) for the circulating gene expression. We also replicated the findings in the FinnGen consortium. RESULTS Genetically proxied levels of 4 plasma proteins (CREB3L4, HDGF, SERPINA3, GNPNAT1) were identified as positively correlated with an increased risk of prostate cancer, while an increase in genetically proxied levels of 5 plasma proteins (TNFRSF6B, GSK3A, EIF4B, CLIC1, SMAD2) were significantly associated with a decreased risk of prostate cancer in the PRACTICAL consortium. Among the identified proteins, the causal effects of six proteins including CREB3L4, HDGF, SERPINA3, TNFRSF6B, EIF4B, and SMAD2 remained significant in the replication analyses in the FinnGen consortium and when combined with meta-analyses (SMAD2: OR 0.710, 95% CI 0.578-0.873, p-value = 0.001; CREB3L4: OR 1.260, 95% CI 1.164-1.364, p-value < 0.0001; HDGF: OR 1.072, 95% CI 1.021-1.125, p-value = 0.005; SERPINA3: OR 1.138, 95% CI 1.091-1.187, p-value < 0.0001; TNFRSF6B: OR 0.656, 95% CI 0.496-0.869, p-value = 0.003; EIF4B: OR 0.701, 95% CI 0.618-0.796, p-value < 0.0001). SMAD2 and CREB3L4 gene expressions proxied with cis-expression quantitative trait loci are also significantly associated with the risk of prostate cancer in both consortiums and when combined with meta-analyses (SMAD2: OR 0.787, 95% CI 0.719-0.861, p-value = 1.00 × 10-4; CREB3L4: OR 1.219, 95% CI 1.033-1.438, p-value = 0.019). CONCLUSIONS Our consistent results highlighted the important roles of plasma SMAD2 and CREB3L4 in the risk of prostate cancer. Further investigations on these proteins may reveal their potential in the prevention and treatment of prostate cancer.
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Affiliation(s)
- Jian Wu
- Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China
| | - Zitong Yang
- Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China
- Department of Urology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, Zhejiang, China
| | - Jiafeng Ding
- Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China
- Department of Urology, Lishui Hospital of Zhejiang University, Lishui, 323000, Zhejiang, China
| | - Sida Hao
- Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China
| | - Hong Chen
- Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China
| | - Ke Jin
- Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China
| | - Cheng Zhang
- Department of Urology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, Zhejiang, China.
| | - Xiangyi Zheng
- Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China.
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Li G, Wang M. Simultaneous clustering and estimation of networks in multiple graphical models. Biostatistics 2024; 26:kxae015. [PMID: 38841872 PMCID: PMC11826093 DOI: 10.1093/biostatistics/kxae015] [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: 07/19/2023] [Revised: 02/17/2024] [Accepted: 05/10/2024] [Indexed: 06/07/2024] Open
Abstract
Gaussian graphical models are widely used to study the dependence structure among variables. When samples are obtained from multiple conditions or populations, joint analysis of multiple graphical models are desired due to their capacity to borrow strength across populations. Nonetheless, existing methods often overlook the varying levels of similarity between populations, leading to unsatisfactory results. Moreover, in many applications, learning the population-level clustering structure itself is of particular interest. In this article, we develop a novel method, called Simultaneous Clustering and Estimation of Networks via Tensor decomposition (SCENT), that simultaneously clusters and estimates graphical models from multiple populations. Precision matrices from different populations are uniquely organized as a three-way tensor array, and a low-rank sparse model is proposed for joint population clustering and network estimation. We develop a penalized likelihood method and an augmented Lagrangian algorithm for model fitting. We also establish the clustering accuracy and norm consistency of the estimated precision matrices. We demonstrate the efficacy of the proposed method with comprehensive simulation studies. The application to the Genotype-Tissue Expression multi-tissue gene expression data provides important insights into tissue clustering and gene coexpression patterns in multiple brain tissues.
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Affiliation(s)
- Gen Li
- Department of Biostatistics, University of Michigan, 1415 Washington Heights, Ann Arbor, MI,48109, United States
| | - Miaoyan Wang
- Department of Statistics, University of Wisconsin, 1300 University Ave, Madison, WI 53706, United States
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Meng Y, Meng Y, Li L, Li Y, He J, Shan Y. The role of DNA methylation in placental development and its implications for preeclampsia. Front Cell Dev Biol 2024; 12:1494072. [PMID: 39691449 PMCID: PMC11649665 DOI: 10.3389/fcell.2024.1494072] [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: 09/10/2024] [Accepted: 11/20/2024] [Indexed: 12/19/2024] Open
Abstract
Preeclampsia (PE) is a prevalent and multifaceted pregnancy disorder, characterized by high blood pressure, edema, proteinuria, and systemic organ dysfunction. It remains one of the leading causes of pregnancy complications, yet its exact origins and pathophysiological mechanisms are not fully understood. Currently, the only definitive treatment is delivery, often requiring preterm termination of pregnancy, which increases neonatal and maternal morbidity and mortality rates, particularly in severe cases. This highlights the urgent need for further research to elucidate its underlying mechanisms and develop targeted interventions. PE is thought to result from a combination of factors, including inflammatory cytokines, trophoblast dysfunction, and environmental influences, which may trigger epigenetic changes, particularly DNA methylation. The placenta, a vital organ for fetal and maternal exchange, plays a central role in the onset of PE. Increasing evidence suggests a strong association between DNA methylation, placental function, and the development of PE. This review focuses on the impact of DNA methylation on placental development and its contribution to PE pathophysiology. It aims to clarify the epigenetic processes essential for normal placental development and explore potential epigenetic biomarkers and therapeutic targets for PE. Such insights could lead to the development of novel preventive and therapeutic strategies for this condition.
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Affiliation(s)
- Yizi Meng
- Department of Obstetrics, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun, China
| | - Yimei Meng
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Linli Li
- Department of Obstetrics, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun, China
| | - Yuan Li
- Department of General Gynecology I, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun, China
| | - Jin He
- Department of Obstetrics, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun, China
| | - Yanhong Shan
- Department of Obstetrics, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun, China
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Deng F, Lei J, Qiu J, Zhao C, Wang X, Li M, Sun M, Zhang M, Gao Q. DNA methylation landscape in pregnancy-induced hypertension: progress and challenges. Reprod Biol Endocrinol 2024; 22:77. [PMID: 38978060 PMCID: PMC11229300 DOI: 10.1186/s12958-024-01248-0] [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: 03/10/2024] [Accepted: 06/24/2024] [Indexed: 07/10/2024] Open
Abstract
Gestational hypertension (PIH), especially pre-eclampsia (PE), is a common complication of pregnancy. This condition poses significant risks to the health of both the mother and the fetus. Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may play a role in initiating the earliest pathophysiology of PIH. This article describes the relationship between DNA methylation and placental trophoblast function, genes associated with the placental microenvironment, the placental vascular system, and maternal blood and vascular function, abnormalities of umbilical cord blood and vascular function in the onset and progression of PIH, as well as changes in DNA methylation in the progeny of PIH, in terms of maternal, fetal, and offspring. We also explore the latest research on DNA methylation-based early detection, diagnosis and potential therapeutic strategies for PIH. This will enable the field of DNA methylation research to continue to enhance our understanding of the epigenetic regulation of PIH genes and identify potential therapeutic targets.
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Affiliation(s)
- Fengying Deng
- Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, P. R. China
| | - Jiahui Lei
- Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, P. R. China
| | - Junlan Qiu
- Department of Oncology and Hematology, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, Jiangsu, 215153, P.R. China
| | - Chenxuan Zhao
- Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, P. R. China
| | - Xietong Wang
- Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China
| | - Min Li
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, P. R. China
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, P. R. China
| | - Miao Sun
- Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China.
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, P. R. China.
| | - Meihua Zhang
- Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China.
| | - Qinqin Gao
- Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China.
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, P. R. China.
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Tsikouras P, Antsaklis P, Nikolettos K, Kotanidou S, Kritsotaki N, Bothou A, Andreou S, Nalmpanti T, Chalkia K, Spanakis V, Iatrakis G, Nikolettos N. Diagnosis, Prevention, and Management of Fetal Growth Restriction (FGR). J Pers Med 2024; 14:698. [PMID: 39063953 PMCID: PMC11278205 DOI: 10.3390/jpm14070698] [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: 06/06/2024] [Revised: 06/22/2024] [Accepted: 06/25/2024] [Indexed: 07/28/2024] Open
Abstract
Fetal growth restriction (FGR), or intrauterine growth restriction (IUGR), is still the second most common cause of perinatal mortality. The factors that contribute to fetal growth restriction can be categorized into three distinct groups: placental, fetal, and maternal. The prenatal application of various diagnostic methods can, in many cases, detect the deterioration of the fetal condition in time because the nature of the above disorder is thoroughly investigated by applying a combination of biophysical and biochemical methods, which determine the state of the embryo-placenta unit and assess the possible increased risk of perinatal failure outcome and potential for many later health problems. When considering the potential for therapeutic intervention, the key question is whether it can be utilized during pregnancy. Currently, there are no known treatment interventions that effectively enhance placental function and promote fetal weight development. Nevertheless, in cases with fetuses diagnosed with fetal growth restriction, immediate termination of pregnancy may have advantages not only in terms of minimizing perinatal mortality but primarily in terms of reducing long-term morbidity during childhood and maturity.
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Affiliation(s)
- Panagiotis Tsikouras
- Department of Obstetrics and Gynecology, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (K.N.); (S.K.); (N.K.); (S.A.); (T.N.); (K.C.); (V.S.); (N.N.)
| | - Panos Antsaklis
- Department of Obstetrics and Gynecology Medical School, University Hospital Alexandra, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Konstantinos Nikolettos
- Department of Obstetrics and Gynecology, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (K.N.); (S.K.); (N.K.); (S.A.); (T.N.); (K.C.); (V.S.); (N.N.)
| | - Sonia Kotanidou
- Department of Obstetrics and Gynecology, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (K.N.); (S.K.); (N.K.); (S.A.); (T.N.); (K.C.); (V.S.); (N.N.)
| | - Nektaria Kritsotaki
- Department of Obstetrics and Gynecology, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (K.N.); (S.K.); (N.K.); (S.A.); (T.N.); (K.C.); (V.S.); (N.N.)
| | - Anastasia Bothou
- Department of Midwifery, School of Health Sciences, University of West Attica (UNIWA), 12243 Athens, Greece; (A.B.); (G.I.)
| | - Sotiris Andreou
- Department of Obstetrics and Gynecology, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (K.N.); (S.K.); (N.K.); (S.A.); (T.N.); (K.C.); (V.S.); (N.N.)
| | - Theopi Nalmpanti
- Department of Obstetrics and Gynecology, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (K.N.); (S.K.); (N.K.); (S.A.); (T.N.); (K.C.); (V.S.); (N.N.)
| | - Kyriaki Chalkia
- Department of Obstetrics and Gynecology, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (K.N.); (S.K.); (N.K.); (S.A.); (T.N.); (K.C.); (V.S.); (N.N.)
| | - Vlasis Spanakis
- Department of Obstetrics and Gynecology, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (K.N.); (S.K.); (N.K.); (S.A.); (T.N.); (K.C.); (V.S.); (N.N.)
| | - George Iatrakis
- Department of Midwifery, School of Health Sciences, University of West Attica (UNIWA), 12243 Athens, Greece; (A.B.); (G.I.)
- Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens and Rea Maternity Hospital, 12462 Athens, Greece
| | - Nikolaos Nikolettos
- Department of Obstetrics and Gynecology, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (K.N.); (S.K.); (N.K.); (S.A.); (T.N.); (K.C.); (V.S.); (N.N.)
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6
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Zheng S, Feng S, Song N, Chen G, Jia Y, Zhang G, Liu M, Li X, Ning Y, Wang D, Jia H. The role of the immune system in depersonalisation disorder. World J Biol Psychiatry 2024; 25:291-303. [PMID: 38679810 DOI: 10.1080/15622975.2024.2346096] [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: 12/11/2023] [Accepted: 04/18/2024] [Indexed: 05/01/2024]
Abstract
OBJECTIVES Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the levels of tumour necrosis factor-α and interleukin associated with the dissociative symptoms. In this study, we aimed to explore the role of the immune system in the pathology of DPD. METHODS We screened the protein expression in serum samples of 30 DPD patients and 32 healthy controls. Using a mass spectrometry-based proteomic approach, we identified differential proteins that were verified in another group of 25 DPD patients and 30 healthy controls using immune assays. Finally, we performed a correlation analysis between the expression of differential proteins and clinical symptoms of patients with DPD. RESULTS We identified several dysregulated proteins in patients with DPD compared to HCs, including decreased levels of C-reactive protein (CRP), complement C1q subcomponent subunit B, apolipoprotein A-IV, and increased levels of alpha-1-antichymotrypsin (SERPINA3). Moreover, the expression of CRP was positively correlated with visuospatial memory and the ability to inhibit cognitive interference of DPD. The expression of SERPINA3 was positively correlated with the ability to inhibit cognitive interference and negatively correlated with the perceptual alterations of DPD. CONCLUSIONS The dysregulation of the immune system may be the underlying biological mechanism in DPD. And the expressions of CRP and SERPINA3 can be the potential predictors for the cognitive performance of DPD.
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Affiliation(s)
- Sisi Zheng
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Sitong Feng
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Nan Song
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Guangyao Chen
- Traditional Chinese Medicine Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
| | - Yuan Jia
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Guofu Zhang
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Min Liu
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Xue Li
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Yanzhe Ning
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Dan Wang
- Inner Mongolia Autonomous Region Mental Health Center, Hohhot, Neimenggu, China
| | - Hongxiao Jia
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
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Rahnavard A, Chatterjee R, Wen H, Gaylord C, Mugusi S, Klatt KC, Smith ER. Molecular epidemiology of pregnancy using omics data: advances, success stories, and challenges. J Transl Med 2024; 22:106. [PMID: 38279125 PMCID: PMC10821542 DOI: 10.1186/s12967-024-04876-7] [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: 02/09/2023] [Accepted: 12/26/2023] [Indexed: 01/28/2024] Open
Abstract
Multi-omics approaches have been successfully applied to investigate pregnancy and health outcomes at a molecular and genetic level in several studies. As omics technologies advance, research areas are open to study further. Here we discuss overall trends and examples of successfully using omics technologies and techniques (e.g., genomics, proteomics, metabolomics, and metagenomics) to investigate the molecular epidemiology of pregnancy. In addition, we outline omics applications and study characteristics of pregnancy for understanding fundamental biology, causal health, and physiological relationships, risk and prediction modeling, diagnostics, and correlations.
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Affiliation(s)
- Ali Rahnavard
- Computational Biology Institute, Milken Institute School of Public Health, The George Washington University, Washington, DC, 20052, USA.
- Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC, 20052, USA.
| | - Ranojoy Chatterjee
- Computational Biology Institute, Milken Institute School of Public Health, The George Washington University, Washington, DC, 20052, USA
- Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC, 20052, USA
| | - Hui Wen
- Computational Biology Institute, Milken Institute School of Public Health, The George Washington University, Washington, DC, 20052, USA
- Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC, 20052, USA
| | - Clark Gaylord
- Computational Biology Institute, Milken Institute School of Public Health, The George Washington University, Washington, DC, 20052, USA
- Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC, 20052, USA
| | - Sabina Mugusi
- Department of Clinical Pharmacology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Kevin C Klatt
- Nutritional Sciences & Toxicology, University of California, Berkeley, CA, 94720, USA
| | - Emily R Smith
- Department of Global Health, The Milken Institute School of Public Health, The George Washington University, Washington, DC, 20052, USA.
- Department of Exercise and Nutrition Sciences, The Milken Institute School of Public Health, The George Washington University, Washington, DC, 20052, USA.
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Fang W, Song Q, Lv T, Lv J, Cai Z, Wang Z, Song X, Ji X, Huang J. Serpina3n/serpina3 alleviates cyclophosphamide-induced interstitial cystitis by activating the Wnt/β-catenin signal. Int Urol Nephrol 2023; 55:3065-3075. [PMID: 37594700 PMCID: PMC10611603 DOI: 10.1007/s11255-023-03726-7] [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: 02/14/2023] [Accepted: 07/25/2023] [Indexed: 08/19/2023]
Abstract
BACKGROUND/OBJECTIVE Serpina3n/Serpina3 has been identified to be implicated in inflammatory diseases, but its role in interstitial cystitis/bladder pain syndrome (IC/BPS) remains unknown. Here, we aimed to reveal serpina3n/serpina3 role in IC/BPS in vivo and in vitro. METHODS The IC/BPS model in mice was induced by intraperitoneal injection of 150 mg/kg of cyclophosphamide (CYP). HE and toluidine blue staining were used for histology assessment. Serpina3n/serpina3 expression in the bladder tissues from IC/BPS patients and mouse models were determined by qPCR, immunohistochemistry and western blotting. XAV-939 treatment was applied to inhibit β-catenin activation. Serpina3 role in modulating the growth and apoptosis of HBlEpCs, a human primary bladder epithelial cell line, was assessed by CCK-8 and flow cytometry assays. RESULTS Serpina3n/serpina3 expression was decreased in both human and mice bladder tissues with IC/BPS. Upregulation of serpina3n significantly alleviated CYP-induced bladder injury, with decreased mast cells and pro-inflammatory factor levels, including IL-1β, IL-6, and TNF-α, while increased IL-10 level. In addition, serpina3 overexpression inhibited the apoptosis of HBlEpCs, and increased cell growth. In mechanism, we found that serpina3 overexpression promoted the activation of wnt/β-catenin signaling. And, the inhibition of wnt/β-catenin signaling with XAV-939 abolished serpina3n/serpina3 role in protecting bladder tissues from CYP-induced cystitis, as well as inhibiting HBlEpC apoptosis. CONCLUSION Serpina3n/serpina3 expression was decreased in IC/BPS. Overexpression of serpina3n could alleviate CYP-induced IC/BPS by activating the Wnt/β-catenin signal. This study may provide a new therapeutic strategy for IC/BPS.
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Affiliation(s)
- Weilin Fang
- Department of Urology and Andrology, Shanghai Pudong New Area Gongli Hospital, No. 219, Miaopu Road, Pudong New District, Shanghai, 200135, China
| | - Qixiang Song
- Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201112, China
| | - Tingting Lv
- Department of Urology and Andrology, Shanghai Pudong New Area Gongli Hospital, No. 219, Miaopu Road, Pudong New District, Shanghai, 200135, China
| | - Jianwei Lv
- Department of Urology and Andrology, Shanghai Pudong New Area Gongli Hospital, No. 219, Miaopu Road, Pudong New District, Shanghai, 200135, China.
| | - Zhikang Cai
- Department of Urology and Andrology, Shanghai Pudong New Area Gongli Hospital, No. 219, Miaopu Road, Pudong New District, Shanghai, 200135, China
| | - Zhong Wang
- Department of Urology and Andrology, Shanghai Pudong New Area Gongli Hospital, No. 219, Miaopu Road, Pudong New District, Shanghai, 200135, China
| | - Xin Song
- Department of Urology and Andrology, Shanghai Pudong New Area Gongli Hospital, No. 219, Miaopu Road, Pudong New District, Shanghai, 200135, China
| | - Xiang Ji
- Department of Urology and Andrology, Shanghai Pudong New Area Gongli Hospital, No. 219, Miaopu Road, Pudong New District, Shanghai, 200135, China
| | - Jin Huang
- Department of Urology and Andrology, Shanghai Pudong New Area Gongli Hospital, No. 219, Miaopu Road, Pudong New District, Shanghai, 200135, China
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Mirzakhani H, Handy DE, Lu Z, Oppenheimer B, Litonjua AA, Loscalzo J, Weiss ST. Integration of circulating microRNAs and transcriptome signatures identifies early-pregnancy biomarkers of preeclampsia. Clin Transl Med 2023; 13:e1446. [PMID: 37905457 PMCID: PMC10616748 DOI: 10.1002/ctm2.1446] [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: 07/24/2023] [Revised: 09/21/2023] [Accepted: 10/01/2023] [Indexed: 11/02/2023] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) have been implicated in the pathobiology of preeclampsia, a common hypertensive disorder of pregnancy. In a nested matched case-control cohort within the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we previously identified peripheral blood mRNA signatures related to preeclampsia and vitamin D status (≤30 ng/mL) during gestation from 10 to 18 weeks, using differential expression analysis. METHODS Using quantitative PCR arrays, we conducted profiling of circulating miRNAs at 10-18 weeks of gestation in the same VDAART cohort to identify differentially expressed (DE) miRNAs associated with preeclampsia and vitamin D status. For the validation of the expression of circulating miRNA signatures in the placenta, the HTR-8/SVneo trophoblast cell line was used. Targets of circulating miRNA signatures in the preeclampsia mRNA signatures were identified by consensus ranking of miRNA-target prediction scores from four sources. The connected component of target signatures was identified by mapping to the protein-protein interaction (PPI) network and hub targets were determined. As experimental validation, we examined the gene and protein expression of IGF1R, one of the key hub genes, as a target of the DE miRNA, miR-182-5p, in response to a miR-182-5p mimic in HTR-8/SVneo cells. RESULTS Pregnant women with preeclampsia had 16 circulating DE miRNAs relative to normal pregnancy controls that were also DE under vitamin D insufficiency (9/16 = 56% upregulated, FDR < .05). Thirteen miRNAs (13/16 = 81.3%) were detected in HTR-8/SVneo cells. Overall, 16 DE miRNAs had 122 targets, of which 87 were unique. Network analysis demonstrated that the 32 targets of DE miRNA signatures created a connected subnetwork in the preeclampsia module with CXCL8, CXCL10, CD274, MMP9 and IGF1R having the highest connectivity and centrality degree. In an in vitro validation experiment, the introduction of an hsa-miR-182-5p mimic resulted in significant reduction of its target IGF1R gene and protein expression within HTR-8/SVneo cells. CONCLUSIONS The integration of the circulating DE miRNA and mRNA signatures associated preeclampsia added additional insights into the subclinical molecular signature of preeclampsia. Our systems and network biology approach revealed several biological pathways, including IGF-1, that may play a role in the early pathophysiology of preeclampsia. These pathways and signatures also denote potential biomarkers for the early stages of preeclampsia and suggest possible preventive measures.
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Affiliation(s)
- Hooman Mirzakhani
- Channing Division of Network MedicineDepartment of MedicineHarvard Medical SchoolBrigham and Women's HospitalBostonMassachusettsUSA
| | - Diane E. Handy
- Division of Cardiovascular MedicineDepartment of MedicineBrigham and Women's HospitalHarvard Medical SchoolBostonMassachusettsUSA
| | - Zheng Lu
- Channing Division of Network MedicineDepartment of MedicineHarvard Medical SchoolBrigham and Women's HospitalBostonMassachusettsUSA
| | - Ben Oppenheimer
- Channing Division of Network MedicineDepartment of MedicineHarvard Medical SchoolBrigham and Women's HospitalBostonMassachusettsUSA
| | - Augusto A. Litonjua
- Division of Pediatric Pulmonary MedicineDepartment of PediatricsGolisano Children's Hospital at StrongUniversity of Rochester Medical CenterRochesterNew YorkUSA
| | - Joseph Loscalzo
- Division of Cardiovascular MedicineDepartment of MedicineBrigham and Women's HospitalHarvard Medical SchoolBostonMassachusettsUSA
| | - Scott T. Weiss
- Channing Division of Network MedicineDepartment of MedicineHarvard Medical SchoolBrigham and Women's HospitalBostonMassachusettsUSA
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10
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Zhou L, Peng F, Li J, Gong H. Exploring novel biomarkers in dilated cardiomyopathy‑induced heart failure by integrated analysis and in vitro experiments. Exp Ther Med 2023; 26:325. [PMID: 37346398 PMCID: PMC10280324 DOI: 10.3892/etm.2023.12024] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 04/12/2023] [Indexed: 06/23/2023] Open
Abstract
Despite the availability of several effective and promising treatment methods, heart failure (HF) remains a significant public health concern that requires advanced therapeutic strategies and techniques. Dilated cardiomyopathy (DCM) is a crucial factor that contributes to the development and deterioration of HF. The aim of the present study was to identify novel biomarkers and biological pathways to enhance the diagnosis and treatment of patients with DCM-induced HF using weighted gene co-expression network analysis (WGCNA). A total of 24 co-expressed gene modules connected with DCM-induced HF were obtained by WGCNA. Among these, the blue module had the highest correlation with DCM-induced HF (r=0.91; P<0.001) and was enriched in the AGE-RAGE signaling pathway in diabetic complications, the p53 and MAPK signaling pathway, adrenergic signaling in cardiomyocytes, the Janus kinase-STAT signaling pathway and cGMP/PKG signaling. Eight key genes, including secreted protein acidic and rich in cysteine-related modular calcium-binding protein 2 (SMOC2), serpin family A member 3 (SERPINA3), myosin heavy chain 6 (MYH6), S100 calcium binding protein A9 (S100A9), tubulin α (TUBA)3E, TUBA3D, lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1) and phospholipase C ε1 (PLCE1), were selected as the therapeutic targets of DCM-induced HF based on WGCNA and differentially expressed gene analysis. Immune cell infiltration analysis revealed that the proportion of naive B cells and CD4-activated memory T cells was markedly upregulated in DCM-induced HF tissues compared with tissues from healthy controls. Furthermore, reverse transcription-quantitative PCR in AC16 human cardiomyocyte cells treated with doxorubicin showed that among the eight key genes, only SERPINA3, MYH6, S100A9, LYVE1 and PLCE1 exhibited expression levels identical to those revealed by bioinformatics analysis, suggesting that these genes may be involved in the development of DCM-induced HF.
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Affiliation(s)
- Lei Zhou
- Department of Cardiology, Jinshan Hospital of Fudan University, Shanghai 201508, P.R. China
- Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
| | - Fei Peng
- Department of Cardiology, Jinshan Hospital of Fudan University, Shanghai 201508, P.R. China
| | - Juexing Li
- Department of Cardiology, Jinshan Hospital of Fudan University, Shanghai 201508, P.R. China
- Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
| | - Hui Gong
- Department of Cardiology, Jinshan Hospital of Fudan University, Shanghai 201508, P.R. China
- Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
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11
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Li Y, Guo L. The versatile role of Serpina3c in physiological and pathological processes: a review of recent studies. Front Endocrinol (Lausanne) 2023; 14:1189007. [PMID: 37288300 PMCID: PMC10242157 DOI: 10.3389/fendo.2023.1189007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Accepted: 05/10/2023] [Indexed: 06/09/2023] Open
Abstract
Murine Serpina3c belongs to the family of serine protease inhibitors (Serpins), clade "A" and its human homologue is SerpinA3. Serpina3c is involved in some physiological processes, including insulin secretion and adipogenesis. In the pathophysiological process, the deletion of Serpina3c leads to more severe metabolic disorders, such as aggravated non-alcoholic fatty liver disease (NAFLD), insulin resistance and obesity. In addition, Serpina3c can improve atherosclerosis and regulate cardiac remodeling after myocardial infarction. Many of these processes are directly or indirectly mediated by its inhibition of serine protease activity. Although its function has not been fully revealed, recent studies have shown its potential research value. Here, we aimed to summarize recent studies to provide a clearer view of the biological roles and the underlying mechanisms of Serpina3c.
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Affiliation(s)
| | - Liang Guo
- School of Exercise and Health and Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, China
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12
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Dai L, Gao F, Wang Q, Lv X, Cheng Z, Wu Y, Chai X, Zetterberg H, Blennow K, Levey AI, Shi J, Shen Y. Molecules of senescent glial cells differentiate Alzheimer's disease from ageing. J Neurol Neurosurg Psychiatry 2023:jnnp-2022-330743. [PMID: 37012067 DOI: 10.1136/jnnp-2022-330743] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 02/28/2023] [Indexed: 04/05/2023]
Abstract
BACKGROUND Ageing is a major risk factor for Alzheimer's disease (AD), which is accompanied by cellular senescence and thousands of transcriptional changes in the brain. OBJECTIVES To identify the biomarkers in the cerebrospinal fluid (CSF) that could help differentiate healthy ageing from neurodegenerative processes. METHODS Cellular senescence and ageing-related biomarkers were assessed in primary astrocytes and postmortem brains by immunoblotting and immunohistochemistry. The biomarkers were measured in CSF samples from the China Ageing and Neurodegenerative Disorder Initiative cohort using Elisa and the multiplex Luminex platform. RESULTS The cyclin-dependent kinase inhibitors p16/p21-positive senescent cells in human postmortem brains were predominantly astrocytes and oligodendrocyte lineage cells, which accumulated in AD brains. CCL2, YKL-40, HGF, MIF, S100B, TSP2, LCN2 and serpinA3 are biomarkers closely related to human glial senescence. Moreover, we discovered that most of these molecules, which were upregulated in senescent glial cells, were significantly elevated in the AD brain. Notably, CSF YKL-40 (β=0.5412, p<0.0001) levels were markedly elevated with age in healthy older individuals, whereas HGF (β=0.2732, p=0.0001), MIF (β=0.33714, p=0.0017) and TSP2 (β=0.1996, p=0.0297) levels were more susceptible to age in older individuals with AD pathology. We revealed that YKL-40, TSP2 and serpinA3 were useful biomarkers for discriminating patients with AD from CN individuals and non-AD patients. DISCUSSION Our findings demonstrated the different patterns of CSF biomarkers related to senescent glial cells between normal ageing and AD, implicating these biomarkers could identify the road node in healthy path off to neurodegeneration and improve the accuracy of clinical AD diagnosis, which would help promote healthy ageing.
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Affiliation(s)
- Linbin Dai
- Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- Neurodegenerative Disorder Research Center, School of Life Sciences, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, People's Republic of China
| | - Feng Gao
- Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Qiong Wang
- Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Xinyi Lv
- Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Zhaozhao Cheng
- Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Yan Wu
- Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Xianliang Chai
- Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Henrik Zetterberg
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
- Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
- Department of Neurodegenerative Disease,UCL Institute of Neurology, Queen Square, London, UK
- UK Dementia Research Institute at UCL, London, UK
- Hong Kong Center for Neurodegenerative Diseases, Hong Kong, People's Republic of China
| | - Kaj Blennow
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
- Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
| | - Allan I Levey
- Department of Neurology, Goizueta Alzheimer's Disease Research Center, Emory University, Atlanta, Georgia, USA
| | - Jiong Shi
- Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Yong Shen
- Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- Neurodegenerative Disorder Research Center, School of Life Sciences, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, People's Republic of China
- Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology, Hefei, Anhui, China
- Centre for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
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13
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Zhang H, Zhang GY, Su WC, Chen YT, Liu YF, Wei D, Zhang YX, Tang QY, Liu YX, Wang SZ, Li WC, Wesselius A, Zeegers MP, Zhang ZY, Gu YH, Tao WA, Yu EYW. High Throughput Isolation and Data Independent Acquisition Mass Spectrometry (DIA-MS) of Urinary Extracellular Vesicles to Improve Prostate Cancer Diagnosis. Molecules 2022; 27:8155. [PMID: 36500247 PMCID: PMC9737666 DOI: 10.3390/molecules27238155] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 11/17/2022] [Accepted: 11/19/2022] [Indexed: 11/25/2022] Open
Abstract
Proteomic profiling of extracellular vesicles (EVs) represents a promising approach for early detection and therapeutic monitoring of diseases such as cancer. The focus of this study was to apply robust EV isolation and subsequent data-independent acquisition mass spectrometry (DIA-MS) for urinary EV proteomics of prostate cancer and prostate inflammation patients. Urinary EVs were isolated by functionalized magnetic beads through chemical affinity on an automatic station, and EV proteins were analyzed by integrating three library-base analyses (Direct-DIA, GPF-DIA, and Fractionated DDA-base DIA) to improve the coverage and quantitation. We assessed the levels of urinary EV-associated proteins based on 40 samples consisting of 20 cases and 20 controls, where 18 EV proteins were identified to be differentiated in prostate cancer outcome, of which three (i.e., SERPINA3, LRG1, and SCGB3A1) were shown to be consistently upregulated. We also observed 6 out of the 18 (33%) EV proteins that had been developed as drug targets, while some of them showed protein-protein interactions. Moreover, the potential mechanistic pathways of 18 significantly different EV proteins were enriched in metabolic, immune, and inflammatory activities. These results showed consistency in an independent cohort with 20 participants. Using a random forest algorithm for classification assessment, including the identified EV proteins, we found that SERPINA3, LRG1, or SCGB3A1 add predictable value in addition to age, prostate size, body mass index (BMI), and prostate-specific antigen (PSA). In summary, the current study demonstrates a translational workflow to identify EV proteins as molecular markers to improve the clinical diagnosis of prostate cancer.
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Affiliation(s)
- Hao Zhang
- State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, Nanjing 210096, China
- EVLiXiR Biotech, Nanjing 210032, China
| | - Gui-Yuan Zhang
- State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, Nanjing 210096, China
- EVLiXiR Biotech, Nanjing 210032, China
| | - Wei-Chao Su
- Department of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China
- Department of Mental Health Research, Xiamen Xianyue Hospital, Xiamen 361012, China
| | - Ya-Ting Chen
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, Nanjing 210009, China
| | - Yu-Feng Liu
- State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, Nanjing 210096, China
- EVLiXiR Biotech, Nanjing 210032, China
- Bell Mountain Molecular MedTech Institute, Nanjing 210032, China
| | - Dong Wei
- State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, Nanjing 210096, China
- Bell Mountain Molecular MedTech Institute, Nanjing 210032, China
| | - Yan-Xi Zhang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, Nanjing 210009, China
| | - Qiu-Yi Tang
- Medical School of Southeast University, Nanjing 210009, China
| | - Yu-Xiang Liu
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, Nanjing 210009, China
| | - Shi-Zhi Wang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
| | - Wen-Chao Li
- Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing 210009, China
| | - Anke Wesselius
- Department of Epidemiology, CAPHRI Care and Public Health Research Institute, Maastricht University, 6229ER Maastricht, The Netherlands
- School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229ER Maastricht, The Netherlands
| | - Maurice P Zeegers
- Department of Epidemiology, CAPHRI Care and Public Health Research Institute, Maastricht University, 6229ER Maastricht, The Netherlands
- School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229ER Maastricht, The Netherlands
| | - Zi-Yu Zhang
- Department of Pathology, Jiangxi Maternal & Child Health Hospital, Nanchang 330006, China
| | - Yan-Hong Gu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
| | - W Andy Tao
- Departments of Chemistry and Biochemistry, Purdue University, West Lafayette, IN 47907, USA
| | - Evan Yi-Wen Yu
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, Nanjing 210009, China
- Department of Epidemiology, CAPHRI Care and Public Health Research Institute, Maastricht University, 6229ER Maastricht, The Netherlands
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14
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Balzanelli MG, Distratis P, Lazzaro R, Pham VH, Tran TC, Dipalma G, Bianco A, Serlenga EM, Aityan SK, Pierangeli V, Nguyen KCD, Inchingolo F, Tomassone D, Isacco CG. Analysis of Gene Single Nucleotide Polymorphisms in COVID-19 Disease Highlighting the Susceptibility and the Severity towards the Infection. Diagnostics (Basel) 2022; 12:diagnostics12112824. [PMID: 36428884 PMCID: PMC9689844 DOI: 10.3390/diagnostics12112824] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/07/2022] [Accepted: 11/10/2022] [Indexed: 11/18/2022] Open
Abstract
Many factors may influence the risk of being infected by SARS-CoV-2, the coronavirus responsible for coronavirus disease 2019 (COVID-19). Exposure to the virus cannot explain the variety of an individual's responses to the virus and the high differences of effect that the virus may cause to some. While a person's preexisting condition and their immune defenses have been confirmed to play a major role in the disease progression, there is still much to learn about hosts' genetic makeup towards COVID-19 susceptibility and risk. The host genetic makeup may have direct influence on the grade of predisposition and outcomes of COVID-19. In this study, we aimed to investigate the presence of relevant genetic single nucleotide polymorphisms (SNPs), the peripheral blood level of IL6, vitamin D and arterial blood gas (ABG) markers (pH, oxygen-SpO2 and carbon dioxide-SpCO2) on two groups, COVID-19 (n = 41, study), and the healthy (n = 43, control). We analyzed cytokine and interleukin genes in charge of both pro-inflammatory and immune-modulating responses and those genes that are considered involved in the COVID-19 progression and complications. Thus, we selected major genes, such as IL1β, IL1RN (IL-1 β and α receptor) IL6, IL6R (IL-6 receptor), IL10, IFNγ (interferon gamma), TNFα (tumor necrosis factor alpha), ACE2 (angiotensin converting enzyme), SERPINA3 (Alpha-1-Antiproteinase, Antitrypsin member of Serpin 3 family), VDR (vitamin D receptor Tak1, Bsm1 and Fok1), and CRP (c-reactive protein). Though more research is needed, these findings may give a better representation of virus pleiotropic activity and its relation to the immune system.
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Affiliation(s)
- Mario Giosuè Balzanelli
- SET-118, Department of Pre-Hospital and Emergency-San Giuseppe Moscati Hospital, 74100 Taranto, Italy
| | - Pietro Distratis
- SET-118, Department of Pre-Hospital and Emergency-San Giuseppe Moscati Hospital, 74100 Taranto, Italy
| | - Rita Lazzaro
- SET-118, Department of Pre-Hospital and Emergency-San Giuseppe Moscati Hospital, 74100 Taranto, Italy
| | - Van Hung Pham
- Department of Microbiology and Virology, Phan Chau Trinh University of Medicine, Danang City 50000, Vietnam
| | - Toai Cong Tran
- Department of Histology, Embryology and Genetics, Pham Ngoc Thach University of Medicine, Ho Chi Minh City 70000, Vietnam
| | - Gianna Dipalma
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70126 Bari, Italy
| | - Angelica Bianco
- Experimental Zooprophylactic Institute of Puglia and Basilicata, 71121 Foggia, Italy
| | - Emilio Maria Serlenga
- Hematology Department, Blood Transfusion Unit, SS Annunnziata Hospital, 74100 Taranto, Italy
| | | | | | - Kieu Cao Diem Nguyen
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70126 Bari, Italy
| | - Francesco Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70126 Bari, Italy
| | - Diego Tomassone
- Foundation of Physics Research Center, 87053 Celico, Italy
- Correspondence:
| | - Ciro Gargiulo Isacco
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70126 Bari, Italy
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15
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Salmeri N, Carbone IF, Cavoretto PI, Farina A, Morano D. Epigenetics Beyond Fetal Growth Restriction: A Comprehensive Overview. Mol Diagn Ther 2022; 26:607-626. [PMID: 36028645 DOI: 10.1007/s40291-022-00611-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2022] [Indexed: 12/30/2022]
Abstract
Fetal growth restriction is a pathological condition occurring when the fetus does not reach the genetically determined growth potential. The etiology of fetal growth restriction is expected to be multifactorial and include fetal, maternal, and placental factors, the latter being the most frequent cause of isolated fetal growth restriction. Severe fetal growth restriction has been related to both an increased risk of perinatal morbidity and mortality, and also a greater susceptibility to developing diseases (especially cardio-metabolic and neurological disorders) later in life. In the last decade, emerging evidence has supported the hypothesis of the Developmental Origin of Health and Disease, which states that individual developmental 'programming' takes place via a delicate fine tuning of fetal genetic and epigenetic marks in response to a large variety of 'stressor' exposures during pregnancy. As the placenta is the maternal-fetal interface, it has a crucial role in fetal programming, such that any perturbation altering placental function interferes with both in-utero fetal growth and also with the adult life phenotype. Several epigenetic mechanisms have been highlighted in modulating the dynamic placental epigenome, including alterations in DNA methylation status, post-translational modification of histones, and non-coding RNAs. This review aims to provide a comprehensive and critical overview of the available literature on the epigenetic background of fetal growth restriction. A targeted research strategy was performed using PubMed, MEDLINE, Embase, and The Cochrane Library up to January 2022. A detailed and fully referenced synthesis of available literature following the Scale for the Assessment of Narrative Review Articles guidelines is provided. A variety of epigenetic marks predominantly interfering with placental development, function, and metabolism were found to be potentially associated with fetal growth restriction. Available evidence on the role of environmental exposures in shaping the placental epigenome and the fetal phenotype were also critically discussed. Because of the highly dynamic crosstalk between epigenetic mechanisms and the extra level of complexity in interpreting the final placental transcriptome, a full comprehension of these phenomenon is still lacking and advances in multi-omics approaches are urgently needed. Elucidating the role of epigenetics in the developmental origins of health and disease represents a new challenge for the coming years, with the goal of providing early interventions and prevention strategies and, hopefully, new treatment opportunities.
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Affiliation(s)
- Noemi Salmeri
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy
| | - Ilma Floriana Carbone
- Unit of Obstetrics, Department of Woman, Child and Neonate, Mangiagalli Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Paolo Ivo Cavoretto
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy
| | - Antonio Farina
- Division of Obstetrics and Prenatal Medicine, Department of Medicine and Surgery (DIMEC), IRCCS Sant'Orsola-Malpighi Hospital, University of Bologna, 40138, Bologna, Italy.
| | - Danila Morano
- Department of Morphology, Surgery and Experimental Medicine, Section of Obstetrics and Gynecology, Azienda Ospedaliero-Universitaria S. Anna, University of Ferrara, Cona, Ferrara, Italy
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16
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Boyang C, Yuexing L, Yiping Y, Haiyang Y, Xufei Z, Liancheng G, Yunzhi C. Construction and analysis of heart failure diagnosis model based on random forest and artificial neural network. Medicine (Baltimore) 2022; 101:e31097. [PMID: 36254001 PMCID: PMC9575800 DOI: 10.1097/md.0000000000031097] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Heart failure is a global health problem and the number of sufferers is increasing as the population grows and ages. Existing diagnostic techniques for heart failure have various limitations in the clinical setting and there is a need to develop a new diagnostic model to complement the existing diagnostic methods. In recent years, with the development and improvement of gene sequencing technology, more genes associated with heart failure have been identified. We screened for differentially expressed genes in heart failure using available gene expression data from the Gene Expression Omnibus database and identified 6 important genes by a random forest classifier (ASPN, MXRA5, LUM, GLUL, CNN1, and SERPINA3). And we have successfully constructed a new heart failure diagnostic model using an artificial neural network and validated its diagnostic efficacy in a public dataset. We calculated heart failure-related differentially expressed genes and obtained 24 candidate genes by random forest classification, and selected the top 6 genes as important genes for subsequent analysis. The prediction weights of the genes of interest were determined by the neural network model and the model scores were evaluated in 2 independent sample datasets (GSE16499 and GSE57338 datasets). Since the weights of RNA-seq predictions for constructing neural network models were theoretically more suitable for disease classification of RNA-seq data, the GSE57338 dataset had the best performance in the validation results. The diagnostic model derived from our study can be of clinical value in determining the likelihood of HF occurring through cardiac biopsy. In the meantime, we need to further investigate the accuracy of the diagnostic model based on the results of our study.
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Affiliation(s)
- Chen Boyang
- School of Preclinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Li Yuexing
- School of Preclinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Yan Yiping
- School of Preclinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Yu Haiyang
- School of Preclinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Zhang Xufei
- School of Preclinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Guan Liancheng
- Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Chen Yunzhi
- School of Preclinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
- * Correspondence: Chen Yunzhi, School of Preclinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China (e-mail: )
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17
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Wang Y, Wang L, Yu X, Gong W. MiR-30a-3p Targeting FLT1 Modulates Trophoblast Cell Proliferation in the Pathogenesis of Preeclampsia. Horm Metab Res 2022; 54:633-640. [PMID: 35981547 DOI: 10.1055/a-1880-1126] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Preeclampsia (PE) may pose significant adverse effects on pregnant women. Dysregulation of angiogenesis, trophoblast invasion, and proliferation are known to be associated with PE development and progression. Fms related tyrosine kinase 1 (FLT1), an anti-angiogenic factor, is consistently upregulated in PE patients. Recent papers highlight that aberrant miR-30a-3p expression contributes to PE development. More effects are needed to assess the biological function of placental miR-30a-3p in PE. The soluble FLT1 (sFLT1) and FLT1 levels were tested by ELISA assay and Western blotting assay. mRNA levels were measured by RT-qPCR assay. Colony formation and MTT assays were applied to assess the effect of miR-30a-3p on trophoblast cell proliferation. The serum sFLT1 and placental FLT1 levels were substantially high in patients with PE. Using miRNA microarray assay, we identified miR-30a-3p upregulation in PE patients' placenta tissues. We further confirmed that miR-30a-3p binds to the 3'-UTR of FLT1 gene and positively regulate its expression. Forcing miR-30a-3p expression inhibited trophoblast cell proliferation and vice versa. In conclusion, persistent high levels of FLT1 and miR-30a-3p may pose adverse effects on angiogenesis and trophoblast proliferation in placenta of PE patients. Therefore, targeting FLT1 and miR-30a-3p may serve as ideal strategies for managing patients with PE.
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Affiliation(s)
- Yuping Wang
- Department of Obstetrics and Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Lanlan Wang
- Department of Obstetrics and Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Xiaoyan Yu
- Department of Obstetrics and Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Wenwen Gong
- Department of Obstetrics and Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
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18
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Soman A, Asha Nair S. Unfolding the cascade of SERPINA3: Inflammation to cancer. Biochim Biophys Acta Rev Cancer 2022; 1877:188760. [PMID: 35843512 DOI: 10.1016/j.bbcan.2022.188760] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 06/23/2022] [Accepted: 07/08/2022] [Indexed: 10/17/2022]
Abstract
SERine Protease INhibitor clade A member 3 (SERPINA3), a member of the SERine-Protease INhibitor (SERPIN) superfamily, principally works as a protease inhibitor in maintaining cellular homeostasis. It is a matricellular acute-phase glycoprotein that appears to be the sole nuclear-binding secretory serpin. Several studies have emerged in recent years demonstrating its link to cancer and disease biology. SERPINA3 seems to have cancer- and compartment-specific biological functions, acting either as a tumour promoter or suppressor in different cancers. However, the localization, mechanism of action and the effectors of SERPINA3 in physiological and pathological scenarios remain obscure. Our review aims to consolidate the current evidence of SERPINA3 in various cancers, highlighting its association with the cancer hallmarks and ratifying its status as an emerging cancer biomarker. The elucidation of SERPINA3-mediated cancer progression and its targeting might shed light on the realm of cancer therapeutics.
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Affiliation(s)
- Anjana Soman
- Cancer Research Program 4, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India; Research Centre, University of Kerala, Thiruvananthapuram, India
| | - S Asha Nair
- Cancer Research Program 4, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
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Sánchez Díaz E, Martínez-Sánchez L, Roldan Tabares M, Jaramillo Jaramillo L. MicroARN: la biología molecular como herramienta de predicción en preeclampsia. CLINICA E INVESTIGACION EN GINECOLOGIA Y OBSTETRICIA 2022. [DOI: 10.1016/j.gine.2021.100740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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20
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A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells. Int J Mol Sci 2022; 23:ijms23062972. [PMID: 35328392 PMCID: PMC8954921 DOI: 10.3390/ijms23062972] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/20/2022] [Accepted: 03/03/2022] [Indexed: 02/06/2023] Open
Abstract
The prevailing general view of acute-phase proteins (APPs) is that they are produced by the liver in response to the stress of the body as part of a systemic acute-phase response. We demonstrated a coordinated, local production of these proteins upon cell stress by the stressed cells. The local, stress-induced APP production has been demonstrated in different tissues (kidney, breast cancer) and with different stressors (hypoxia, fibrosis and electromagnetic heat). Thus, this local acute-phase response (APR) seems to be a universal mechanism. APP production is an ancient defense mechanism observed in nematodes and fruit flies as well. Local APP production at the tissue level is also supported by sporadic literature data for single proteins; however, the complex, coordinated, local appearance of this stress response has been first demonstrated only recently. Although a number of literature data are available for the local production of single acute-phase proteins, their interpretation as a local, coordinated stress response is new. A better understanding of the role of APPs in cellular stress response may also be of diagnostic/prognostic and therapeutic significance.
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21
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Nowakowska BA, Pankiewicz K, Nowacka U, Niemiec M, Kozłowski S, Issat T. Genetic Background of Fetal Growth Restriction. Int J Mol Sci 2021; 23:ijms23010036. [PMID: 35008459 PMCID: PMC8744929 DOI: 10.3390/ijms23010036] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/17/2021] [Accepted: 12/19/2021] [Indexed: 12/14/2022] Open
Abstract
Fetal growth restriction (FGR) is one of the most formidable challenges in present-day antenatal care. Pathological fetal growth is a well-known factor of not only in utero demise in the third trimester, but also postnatal morbidity and unfavorable developmental outcomes, including long-term sequalae such as metabolic diseases, diabetic mellitus or hypertension. In this review, the authors present the current state of knowledge about the genetic disturbances responsible for FGR diagnosis, divided into fetal, placental and maternal causes (including preeclampsia), as well as their impact on prenatal diagnostics, with particular attention on chromosomal microarray (CMA) and noninvasive prenatal testing technique (NIPT).
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Affiliation(s)
- Beata Anna Nowakowska
- Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland;
- Correspondence: (B.A.N.); (K.P.); Tel.: +48-22-3277131 (B.A.N.); +48-22-3277044 (K.P.)
| | - Katarzyna Pankiewicz
- Department of Obstetrics and Gynecology, Institute of Mother and Child in Warsaw, Kasprzaka 17a, 01-211 Warsaw, Poland; (U.N.); (S.K.); (T.I.)
- Correspondence: (B.A.N.); (K.P.); Tel.: +48-22-3277131 (B.A.N.); +48-22-3277044 (K.P.)
| | - Urszula Nowacka
- Department of Obstetrics and Gynecology, Institute of Mother and Child in Warsaw, Kasprzaka 17a, 01-211 Warsaw, Poland; (U.N.); (S.K.); (T.I.)
| | - Magdalena Niemiec
- Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland;
| | - Szymon Kozłowski
- Department of Obstetrics and Gynecology, Institute of Mother and Child in Warsaw, Kasprzaka 17a, 01-211 Warsaw, Poland; (U.N.); (S.K.); (T.I.)
| | - Tadeusz Issat
- Department of Obstetrics and Gynecology, Institute of Mother and Child in Warsaw, Kasprzaka 17a, 01-211 Warsaw, Poland; (U.N.); (S.K.); (T.I.)
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22
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Yuan Q, Wang S, Zhang G, He J, Liu Z, Wang M, Cai H, Wan J. Highly expressed of SERPINA3 indicated poor prognosis and involved in immune suppression in glioma. IMMUNITY INFLAMMATION AND DISEASE 2021; 9:1618-1630. [PMID: 34449972 PMCID: PMC8589354 DOI: 10.1002/iid3.515] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/29/2021] [Accepted: 08/13/2021] [Indexed: 12/19/2022]
Abstract
Introduction The prognosis of patients with glioma is dismal. It has been reported that Serpin peptidase inhibitor clade A member 3 (SERPINA3) is associated with the mobility and invasion of tumor cells. Our study was designed to explore the value of SERPINA3 messenger RNA (mRNA) expression in the biological process, prognosis, and immune significance in glioma. Methods We analyzed the biological functions of SERPINA3 through data from the Chinese Glioma Genome Atlas databases. Differentially expressed genes and enrichment analysis were performed and correlations between SERPINA3 expression and immune cell infiltration were analyzed. Further, we validated the expression and the survival prediction role of SERPINA3 by using tissue microarrays and RNAscope in situ hybridization in 321 gliomas. The correlations between the expression and clinical‐pathological parameters as well as other biomarkers were examined. Results Univariate and multivariate regression both indicated that the level of SERPINA3 transcript represented an independent prognostic factor. High levels of SERPINA3 correlated with poor survival in patients with glioma. Expression of SERPINA3 mRNA was observed positively correlated with MCM6, IGFBP2, and FKBP10. Enrichment analysis showed SERPINA3 mainly enriched in immune‐related terms and signaling pathways including MAPK, TNF, P53, PI3K‐Akt, nuclear factor‐κB. Immune infiltration analysis further declare the SERPINA3 expression negatively correlated with levels of Macrophages M1, native CD4+ T cell, monocytes, and Mast cell activated. And overexpression of SERPINA3 correlated with low CD4+ T cell infiltration in glioma tissues. Conclusions SERPINA3 may play a key role in the biological process of glioma cells especially in immune suppression activities. SERPINA3 may serve as an independent survival prediction factor in glioma patients.
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Affiliation(s)
- Qing Yuan
- Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Song‐Quan Wang
- Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Guang‐Tao Zhang
- Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jie He
- Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Zhi‐Dan Liu
- Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Ming‐Rong Wang
- State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Hong‐Qing Cai
- Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jing‐Hai Wan
- Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
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23
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Endocrine and molecular milieus of ovarian follicles are diversely affected by human chorionic gonadotropin and gonadotropin-releasing hormone in prepubertal and mature gilts. Sci Rep 2021; 11:13465. [PMID: 34188064 PMCID: PMC8242046 DOI: 10.1038/s41598-021-91434-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 05/18/2021] [Indexed: 12/25/2022] Open
Abstract
Different strategies are used to meet optimal reproductive performance or manage reproductive health. Although exogenous human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) agonists (A) are commonly used to trigger ovulation in estrous cycle synchronization, little is known about their effect on the ovarian follicle. Here, we explored whether hCG- and GnRH-A-induced native luteinizing hormone (LH) can affect the endocrine and molecular milieus of ovarian preovulatory follicles in pigs at different stages of sexual development. We collected ovaries 30 h after hCG/GnRH-A administration from altrenogest and pregnant mare serum gonadotropin (eCG)-primed prepubertal and sexually mature gilts. Several endocrine and molecular alternations were indicated, including broad hormonal trigger-induced changes in follicular fluid steroid hormones and prostaglandin levels. However, sexual maturity affected only estradiol levels. Trigger- and/or maturity-dependent changes in the abundance of hormone receptors (FSHR and LHCGR) and proteins associated with lipid metabolism and steroidogenesis (e.g., STAR, HSD3B1, and CYP11A1), prostaglandin synthesis (PTGS2 and PTGFS), extracellular matrix remodeling (MMP1 and TIMP1), protein folding (HSPs), molecular transport (TF), and cell function and survival (e.g., VIM) were observed. These data revealed different endocrine properties of exogenous and endogenous gonadotropins, with a potent progestational/androgenic role of hCG and estrogenic/pro-developmental function of LH.
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Wang D, Wen Y, Zhang Z, Yang S, Liu X, Cai C, An Q, Lyu S, He H, Xie J, Lei C, Chen H, Ru B, Wang E, Huang Y. DNA methylation status of SERPINA3 gene involved in mRNA expression in three cattle breeds. Anim Biotechnol 2021; 33:1289-1295. [PMID: 33847248 DOI: 10.1080/10495398.2021.1886944] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
DNA methylation could take part in the gene expression and acts an important role in muscle development. In this study, DNA methylation and expression in adipose and muscle tissues were examined at the same time to evaluate the extent of epigenetic modifications and gene expression on the differentially methylated region (DMR) in SERPINA3. Chain reaction of bisulfite sequencing polymerase (BSP) was used to compared difference among DNA methylation patterns. The result of quantitative real-time PCR (qPCR) analysis showed that there was an extensive expression of SERPINA3 gene in tissue and there was a significant difference existing in muscle and adipose between Jiaxian cattle and individual of other breeds with increasing hybridization (p < 0.05). The statistic analyses indicated that DNA methylation patterns had a significant influence to the level of mRNA in tissue of fat and muscle. This study may be an important reference for investigating development of muscle tissue in cattle, and may promote the process of cattle molecular breeding.
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Affiliation(s)
- Dahui Wang
- College of Agriculture and Forestry Engineering, Tongren Unviersity, Tongren, Guizhou, People's Republic of China
| | - Yifan Wen
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Zijing Zhang
- Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou, Henan, People's Republic of China
| | - Shizhen Yang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Xian Liu
- Henan Provincial Animal Husbandry General Station, Zhengzhou, Henan, People's Republic of China
| | - Cuicui Cai
- Guyuan Branch of Ningxia Academy of Agriculture and Forestry Sciences, Guyuan, Ningxia, People's Republic of China
| | - Qingming An
- College of Agriculture and Forestry Engineering, Tongren Unviersity, Tongren, Guizhou, People's Republic of China
| | - Shijie Lyu
- Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou, Henan, People's Republic of China
| | - Hua He
- College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Jianliang Xie
- Guyuan Branch of Ningxia Academy of Agriculture and Forestry Sciences, Guyuan, Ningxia, People's Republic of China
| | - ChuZhao Lei
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Hong Chen
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Baorui Ru
- Henan Provincial Animal Husbandry General Station, Zhengzhou, Henan, People's Republic of China
| | - Eryao Wang
- Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou, Henan, People's Republic of China
| | - Yongzhen Huang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
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Schvarcz CA, Danics L, Krenács T, Viana P, Béres R, Vancsik T, Nagy Á, Gyenesei A, Kun J, Fonović M, Vidmar R, Benyó Z, Kaucsár T, Hamar P. Modulated Electro-Hyperthermia Induces a Prominent Local Stress Response and Growth Inhibition in Mouse Breast Cancer Isografts. Cancers (Basel) 2021; 13:1744. [PMID: 33917524 PMCID: PMC8038813 DOI: 10.3390/cancers13071744] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/20/2021] [Accepted: 03/24/2021] [Indexed: 02/07/2023] Open
Abstract
Modulated electro-hyperthermia (mEHT) is a selective cancer treatment used in human oncology complementing other therapies. During mEHT, a focused electromagnetic field (EMF) is generated within the tumor inducing cell death by thermal and nonthermal effects. Here we investigated molecular changes elicited by mEHT using multiplex methods in an aggressive, therapy-resistant triple negative breast cancer (TNBC) model. 4T1/4T07 isografts inoculated orthotopically into female BALB/c mice were treated with mEHT three to five times. mEHT induced the upregulation of the stress-related Hsp70 and cleaved caspase-3 proteins, resulting in effective inhibition of tumor growth and proliferation. Several acute stress response proteins, including protease inhibitors, coagulation and heat shock factors, and complement family members, were among the most upregulated treatment-related genes/proteins as revealed by next-generation sequencing (NGS), Nanostring and mass spectrometry (MS). pathway analysis demonstrated that several of these proteins belong to the response to stimulus pathway. Cell culture treatments confirmed that the source of these proteins was the tumor cells. The heat-shock factor inhibitor KRIBB11 reduced mEHT-induced complement factor 4 (C4) mRNA increase. In conclusion, mEHT monotherapy induced tumor growth inhibition and a complex stress response. Inhibition of this stress response is likely to enhance the effectiveness of mEHT and other cancer treatments.
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Affiliation(s)
- Csaba András Schvarcz
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (C.A.S.); (L.D.); (P.V.); (R.B.); (T.V.); (Z.B.); (T.K.)
| | - Lea Danics
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (C.A.S.); (L.D.); (P.V.); (R.B.); (T.V.); (Z.B.); (T.K.)
| | - Tibor Krenács
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary;
| | - Pedro Viana
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (C.A.S.); (L.D.); (P.V.); (R.B.); (T.V.); (Z.B.); (T.K.)
| | - Rita Béres
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (C.A.S.); (L.D.); (P.V.); (R.B.); (T.V.); (Z.B.); (T.K.)
| | - Tamás Vancsik
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (C.A.S.); (L.D.); (P.V.); (R.B.); (T.V.); (Z.B.); (T.K.)
| | - Ákos Nagy
- Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary;
| | - Attila Gyenesei
- Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; (A.G.); (J.K.)
| | - József Kun
- Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; (A.G.); (J.K.)
- Department of Pharmacology and Pharmacotherapy, Medical School & Szentágothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of Pécs, H-7624 Pécs, Hungary
| | - Marko Fonović
- Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia; (M.F.); (R.V.)
| | - Robert Vidmar
- Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia; (M.F.); (R.V.)
| | - Zoltán Benyó
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (C.A.S.); (L.D.); (P.V.); (R.B.); (T.V.); (Z.B.); (T.K.)
| | - Tamás Kaucsár
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (C.A.S.); (L.D.); (P.V.); (R.B.); (T.V.); (Z.B.); (T.K.)
| | - Péter Hamar
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (C.A.S.); (L.D.); (P.V.); (R.B.); (T.V.); (Z.B.); (T.K.)
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Gong L, Zhao H, Cui Y, Li X. Transcriptome analysis of placentae reveals HELLP syndrome exhibits a greater extent of placental metabolic dysfunction than preeclampsia. Hypertens Pregnancy 2021; 40:134-143. [PMID: 33818250 DOI: 10.1080/10641955.2021.1908348] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Objective: The association between HELLP syndrome and preeclampsia has been investigated with conflicting conclusions. This study is to investigate the pathogenesis underlying these two diseases by analyzing placental transcriptome.Methods: The gene expression profile downloaded from Gene Expression Omnibus database was analyzed by R language.Results: A total of 573 differentially expressed genes in HELLP syndrome and 358 in preeclampsia were identified, among which 295 were unique to HELLP syndrome. Some metabolism-associated pathways were uniquely enriched in HELLP syndrome.Conclusions: HELLP syndrome exhibits a greater extent of placental metabolic dysfunction than preeclampsia, although these two diseases might share partial pathogenesis.
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Affiliation(s)
- Lili Gong
- Department of Obstetrics, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.,Department of Obstetrics, The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Huanqiang Zhao
- Department of Obstetrics, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.,Department of Obstetrics, The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Yutong Cui
- Department of Obstetrics, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.,Department of Obstetrics, The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Xiaotian Li
- Department of Obstetrics, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.,Department of Obstetrics, The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China.,Department of Obstetrics, The Shanghai Key Laboratory of Birth Defects, Shanghai, China.,Department of Obstetrics, Institutes of Biochemical Sciences, Fudan University, Shanghai, China
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Current knowledge on genetic variants shaping placental transcriptome and their link to gestational and postnatal health. Placenta 2021; 116:2-11. [PMID: 33663810 DOI: 10.1016/j.placenta.2021.02.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 01/15/2021] [Accepted: 02/16/2021] [Indexed: 12/12/2022]
Abstract
Despite the indispensable role of the placenta in the successful course of pregnancy, regulation of its dynamic transcriptome is still underexplored. The purpose of this literature review was to give an overview and draw attention to the contribution of genetic variation in shaping the human placental gene expression. Studies of placental transcriptome shaped by chromosomal variants are limited and may be confounded by cellular mosaicism and somatic genomic rearrangements. Even in relatively simple cases, such as aneuploidies, the placental transcriptome appears to differ from the assumed systematically increased transcript levels of the involved chromosomes. Single nucleotide variants modulating placental gene expression referred to as expression quantitative trait loci (eQTLs) have been analyzed only in ten candidate gene and three genome-wide association studies (GWAS). The latter identified 417 confident placental eGenes, supported by at least two independent studies. Functional profiling of eGenes highlighted biological pathways important in pregnancy, such as immune response or transmembrane transport activity. A fraction of placental eQTLs (1-3%) co-localize with GWAS loci for adult disorders (metabolic, immunological, neurological), suggesting a co-contributory role of the placenta in the developmental programming of health. Some placental eQTLs have been identified as risk factors for adverse pregnancy outcomes, such as rs4769613 (C > T), located near the FLT1 gene and confidently associated with preeclampsia. More studies are needed to map genetic variants shaping gene expression in different placental cell types across three trimesters in normal and complicated gestations and to clarify to what extent these heritable factors contribute to maternal and offspring disease risks.
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Nuh AM, You Y, Ma M. Information on dysregulation of microRNA in placenta linked to preeclampsia. Bioinformation 2021; 17:240-248. [PMID: 34393443 PMCID: PMC8340720 DOI: 10.6026/97320630017240] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/30/2021] [Accepted: 01/31/2021] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs are single-stranded, non-coding RNA molecules, regulate gene expression at the post-transcriptional level. They are expressed in the human body and have a significant impact on the different processes of pathological illness. A developing placenta undergoes a series of stages after successful fertilization, such as cell division, migration, adhesion, apoptosis, and angiogenesis. MicroRNAs dysregulation in placenta has been linked to pregnancy-related complications such as preeclampsia. Therefore, it is of interest to document known information (list of microRNA) on this issue in the development of biological tools for diagnosis, treatment and prevention of the disease.
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Affiliation(s)
- Abdifatah Mohamed Nuh
- Department of Obstetrics, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, 225000, China
- Yangzhou University Medical College, Yangzhou, Jiangsu Province, 225000, China
| | - Yan You
- Department of Obstetrics, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, 225000, China
- Yangzhou University Medical College, Yangzhou, Jiangsu Province, 225000, China
| | - Min Ma
- Department of Obstetrics, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, 225000, China
- Yangzhou University Medical College, Yangzhou, Jiangsu Province, 225000, China
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29
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Lin YH, Platt MP, Fu H, Gui Y, Wang Y, Gonzalez-Juarbe N, Zhou D, Yu Y. Global Proteome and Phosphoproteome Characterization of Sepsis-induced Kidney Injury. Mol Cell Proteomics 2020; 19:2030-2047. [PMID: 32963032 PMCID: PMC7710145 DOI: 10.1074/mcp.ra120.002235] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 09/14/2020] [Indexed: 12/11/2022] Open
Abstract
Sepsis-induced acute kidney injury (S-AKI) is the most common complication in hospitalized and critically ill patients, highlighted by a rapid decline of kidney function occurring a few hours or days after sepsis onset. Systemic inflammation elicited by microbial infections is believed to lead to kidney damage under immunocompromised conditions. However, although AKI has been recognized as a disease with long-term sequelae, partly because of the associated higher risk of chronic kidney disease (CKD), the understanding of kidney pathophysiology at the molecular level and the global view of dynamic regulations in situ after S-AKI, including the transition to CKD, remains limited. Existing studies of S-AKI mainly focus on deriving sepsis biomarkers from body fluids. In the present study, we constructed a mid-severity septic murine model using cecal ligation and puncture (CLP), and examined the temporal changes to the kidney proteome and phosphoproteome at day 2 and day 7 after CLP surgery, corresponding to S-AKI and the transition to CKD, respectively, by employing an ultrafast and economical filter-based sample processing method combined with the label-free quantitation approach. Collectively, we identified 2,119 proteins and 2950 phosphosites through multi-proteomics analyses. Among them, we identified an array of highly promising candidate marker proteins indicative of disease onset and progression accompanied by immunoblot validations, and further denoted the pathways that are specifically responsive to S-AKI and its transition to CKD, which include regulation of cell metabolism regulation, oxidative stress, and energy consumption in the diseased kidneys. Our data can serve as an enriched resource for the identification of mechanisms and biomarkers for sepsis-induced kidney diseases.
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Affiliation(s)
- Yi-Han Lin
- Infectious Diseases and Genomic Medicine Group, J. Craig Venter Institute, Rockville, Maryland
| | - Maryann P Platt
- Infectious Diseases and Genomic Medicine Group, J. Craig Venter Institute, Rockville, Maryland
| | - Haiyan Fu
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Yuan Gui
- Division of Nephrology, Department of Medicine, University of Connecticut School of medicine, Farmington, Connecticut
| | - Yanlin Wang
- Division of Nephrology, Department of Medicine, University of Connecticut School of medicine, Farmington, Connecticut
| | | | - Dong Zhou
- Division of Nephrology, Department of Medicine, University of Connecticut School of medicine, Farmington, Connecticut; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
| | - Yanbao Yu
- Infectious Diseases and Genomic Medicine Group, J. Craig Venter Institute, Rockville, Maryland.
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30
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Khan S, Longhurst H. Epigenetic alterations on C1-inhibitor expression may influence hereditary angioedema attack frequency and C4 levels: Comment on: Karagianni P, Goules AV, Tzioufas AG. Epigenetic alterations in Sjogren's syndrome patient saliva. Clin Exp Immunol 2020; 202:144-145. [PMID: 32940350 PMCID: PMC7597606 DOI: 10.1111/cei.13516] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 08/25/2020] [Accepted: 08/26/2020] [Indexed: 12/29/2022] Open
Abstract
Epigenetic studies reveal how our genes (nature) are influenced by environment (nurture) leading to wide variability in clinical presentations, especially in autoimmune diseases. Patients with C1-inhibitor deficiency, even within the same family, have diverse clinical presentations that may reflect epigenetic control of gene expression by hormones or inflammatory signals.
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Affiliation(s)
- S. Khan
- Department of Immunology and AllergyCastle Hill HospitalHull University Teaching Hospitals NHS TrustCottinghamUK
| | - H. Longhurst
- Department of Clinical ImmunologyAddenbrooke’s HospitalCambridge University Hospitals NHS Foundation TrustCambridgeUK
- University College London HospitalsLondonUK
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31
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Hołda MK, Stachowicz A, Suski M, Wojtysiak D, Sowińska N, Arent Z, Palka N, Podolec P, Kopeć G. Myocardial proteomic profile in pulmonary arterial hypertension. Sci Rep 2020; 10:14351. [PMID: 32873862 PMCID: PMC7462861 DOI: 10.1038/s41598-020-71264-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 07/31/2020] [Indexed: 01/04/2023] Open
Abstract
Pulmonary arterial hypertension (PAH) is a rare, fatal, and incurable disorder. Although advances in the understanding of the PAH pathobiology have been seen in recent years, molecular processes underlying heart remodelling over the course of PAH are still insufficiently understood. Therefore, the aim of this study was to investigate myocardial proteomic profile of rats at different stages of monocrotaline-induced PAH. Samples of left and right ventricle (LV and RV) free wall collected from 32 Wistar rats were subjected to proteomic analysis using an isobaric tag for relative quantitation method. Hemodynamic parameters indicated development of mild elevation of pulmonary artery pressure in the early PAH group (27.00 ± 4.93 mmHg) and severe elevation in the end-stage PAH group (50.50 ± 11.56 mmHg). In early PAH LV myocardium proteins that may be linked to an increase in inflammatory response, apoptosis, glycolytic process and decrease in myocardial structural proteins were differentially expressed compared to controls. During end-stage PAH an increase in proteins associated with apoptosis, fibrosis and cardiomyocyte Ca2+ currents as well as decrease in myocardial structural proteins were observed in LV. In RV during early PAH, especially proteins associated with myocardial structural components and fatty acid beta-oxidation pathway were upregulated. During end-stage PAH significant changes in RV proteins abundance related to the increased myocardial structural components, intensified fibrosis and glycolytic processes as well as decreased proteins related to cardiomyocyte Ca2+ currents were observed. At both PAH stages changes in RV proteins linked to apoptosis inhibition were observed. In conclusion, we identified changes of the levels of several proteins and thus of the metabolic pathways linked to the early and late remodelling of the left and right ventricle over the course of monocrotaline-induced PAH to delineate potential therapeutic targets for the treatment of this severe disease.
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Affiliation(s)
- Mateusz K Hołda
- HEART - Heart Embryology and Anatomy Research Team, Department of Anatomy, Jagiellonian University Medical College, Kopernika 12, 31-034, Kraków, Poland.
- Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, Kraków, Poland.
- Division of Cardiovascular Sciences, The University of Manchester, Manchester, UK.
| | - Aneta Stachowicz
- Department of Pharmacology, Jagiellonian University Medical College, Kraków, Poland
| | - Maciej Suski
- Department of Pharmacology, Jagiellonian University Medical College, Kraków, Poland
| | - Dorota Wojtysiak
- Department of Animal Genetics, Breeding and Ethology, University of Agriculture in Cracow, Kraków, Poland
| | - Natalia Sowińska
- Center of Experimental and Innovative Medicine, University Center of Veterinary Medicine JU-AU, University of Agriculture in Cracow, Kraków, Poland
| | - Zbigniew Arent
- Center of Experimental and Innovative Medicine, University Center of Veterinary Medicine JU-AU, University of Agriculture in Cracow, Kraków, Poland
| | - Natalia Palka
- Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, Kraków, Poland
| | - Piotr Podolec
- Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, Kraków, Poland
| | - Grzegorz Kopeć
- Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, Kraków, Poland
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Rajasekaran S, Tangavel C, Soundararajan DCR, Nayagam SM, Matchado MS, Muthurajan R, Anand KSSV, Rajendran S, Shetty AP, Kanna RM, Kuppamuthu D. Proteomic Signatures of Healthy Intervertebral Discs From Organ Donors: A Comparison With Previous Studies on Discs From Scoliosis, Animals, and Trauma. Neurospine 2020; 17:426-442. [PMID: 32615701 PMCID: PMC7338947 DOI: 10.14245/ns.2040056.028] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 03/02/2020] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE To catalog and characterize the proteome of normal human intervertebral disc (IVD). METHODS Nine magnetic resonance imaging (MRI) normal IVDs were harvested from 9 different brain dead yet alive voluntary organ donors and were subjected to electrospray ionization-liquid chromatography tandem mass spectrometry (ESI-LC-MS/MS) acquisition. RESULTS A total of 1,116 proteins were identified. Functional enrichment analysis tool DAVID ver. 6.8 categorized: extracellular proteins (38%), intracellular (31%), protein-containing complex (13%), organelle (9%), membrane proteins (6%), supramolecular complex (2%), and 1% in the cell junction. Molecular function revealed: binding activity (42%), catalytic activity (31%), regulatory activity (14%), and structural activity (7%). Molecular transducer, transporter, and transcription regulator activity together contributed to 6%. A comparison of the proteins obtained from this study to others in the literature showed a wide variation in content with only 3% of bovine, 5% of murine, 54% of human scoliotic discs, and 10.2% of discs adjacent to lumbar burst fractures common to our study of organ donors. Between proteins reported in scoliosis and lumbar fracture patients, only 13.51% were common, further signifying the contrast amongst the various MRI normal IVD samples. CONCLUSION The proteome of "healthy" human IVDs has been defined, and our results show that proteomic data on IVDs obtained from scoliosis, fracture patients, and cadavers lack normal physiological conditions and should not be used as biological controls despite normal MRI findings. This questions the validity of previous studies that have used such discs as controls for analyzing the pathomechanisms of disc degeneration.
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Affiliation(s)
| | | | | | | | | | - Raveendran Muthurajan
- Department of Plant Biotechnology, Tamil Nadu Agricultural University, Coimbatore, India
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Basak S, Srinivas V, Mallepogu A, Duttaroy AK. Curcumin stimulates angiogenesis through VEGF and expression of HLA‐G in first‐trimester human placental trophoblasts. Cell Biol Int 2020; 44:1237-1251. [DOI: 10.1002/cbin.11324] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Accepted: 02/16/2020] [Indexed: 12/26/2022]
Affiliation(s)
- Sanjay Basak
- Department of Nutrition, Faculty of MedicineUniversity of Oslo POB 1046, Blindern N‐0316 Oslo Norway
- ICMR‐National Institute of Nutrition Hyderabad Telangana 500007 India
| | | | - Aswani Mallepogu
- ICMR‐National Institute of Nutrition Hyderabad Telangana 500007 India
| | - Asim K. Duttaroy
- Department of Nutrition, Faculty of MedicineUniversity of Oslo POB 1046, Blindern N‐0316 Oslo Norway
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34
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Li Q, Zeng H, Zhao Y, Gong Y, Ma X. Proteomic Analysis of Cerebrospinal Fluid From Patients With Extranodal NK-/T-Cell Lymphoma of Nasal-Type With Ethmoidal Sinus Metastasis. Front Oncol 2020; 9:1489. [PMID: 31998645 PMCID: PMC6966716 DOI: 10.3389/fonc.2019.01489] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 12/11/2019] [Indexed: 02/05/2023] Open
Abstract
Objective: Extranodal natural killer /T-cell lymphoma (ENKTL) is an aggressive and unusual subtype of non-Hodgkin lymphoma (NHL) that it is related with the Epstein-Barr virus (EBV). CSF is considered as an ideal source of high-concenrtation disease-related proteins. We aimed at identifying the proteomic markers changes of CSF in ENKTL patients and used such changes to diagnose ENKTL. Materials and methods: In this study, CSF samples were acquired from hospitalization patients from the Cancer Center of West China Hospital, Chengdu, China. Comparative proteomic profiling are commonly used to do label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). And in this study the same method was used to characterize the variety of proteins in ENKTL patients and none-ENKTL people. Results: In the aggregate, 421 non-excrescent and functional proteins were identified among the samples. Of these proteins, 45 proteins quantified match the involved criteria. HRG, TIMP-1, SERPINA3, FGA, FGG, TF, FGB, APP, and AGT were significantly up-regulated. Discussion: We discovered that some proteins were significantly up-regulated. Also, these proteins themselves or with others proteins may be potential markers to diagnose ENKTL. The changes of proteomics may be a potential method to precisely identify the pathogenesis of the ENKTL.
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Affiliation(s)
- Qingfang Li
- State Key Laboratory of Biotherapy, Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Hao Zeng
- State Key Laboratory of Biotherapy, Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yunuo Zhao
- State Key Laboratory of Biotherapy, Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yanqiu Gong
- State Key Laboratory of Biotherapy, Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xuelei Ma
- State Key Laboratory of Biotherapy, Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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Perico N, Askenazi D, Cortinovis M, Remuzzi G. Maternal and environmental risk factors for neonatal AKI and its long-term consequences. Nat Rev Nephrol 2019; 14:688-703. [PMID: 30224767 DOI: 10.1038/s41581-018-0054-y] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Acute kidney injury (AKI) is a common and life-threatening complication in critically ill neonates. Gestational risk factors for AKI include premature birth, intrauterine growth restriction and low birthweight, which are associated with poor nephron development and are often the consequence of pre-gestational and gestational factors, such as poor nutritional status. Our understanding of how to best optimize renal development and prevent AKI is in its infancy; however, the identification of pre-gestational and gestational factors that increase the risk of adverse neonatal outcomes and the implementation of interventions, such as improving nutritional status early in pregnancy, have the potential to optimize fetal growth and reduce the risk of preterm birth, thereby improving kidney health. The overall risk of AKI among critically ill and premature neonates is exacerbated postnatally as these infants are often exposed to dehydration, septic shock and potentially nephrotoxic medications. Strategies to improve outcomes - for example, through careful evaluation of nephrotoxic drugs - may reduce the incidence of AKI and its consequences among this population. Management strategies and updated technology that will support neonates with AKI are greatly needed. Extremely premature infants and those who survive an episode of AKI should be screened for chronic kidney disease until early adulthood. Here, we provide an overview of our current understanding of neonatal AKI, focusing on its relationship to preterm birth and growth restriction. We describe factors that prevent optimal nephrogenesis during pregnancy and provide a framework for future explorations designed to maximize outcomes in this vulnerable population.
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Affiliation(s)
- Norberto Perico
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
| | - David Askenazi
- Pediatric and Infant Center for Acute Nephrology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Monica Cortinovis
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
| | - Giuseppe Remuzzi
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy. .,Unit of Nephrology and Dialysis, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy. .,L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
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Zhou ML, Chen FS, Mao H. Clinical significance and role of up-regulation of SERPINA3 expression in endometrial cancer. World J Clin Cases 2019; 7:1996-2002. [PMID: 31423431 PMCID: PMC6695533 DOI: 10.12998/wjcc.v7.i15.1996] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 06/19/2019] [Accepted: 07/03/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Serpin peptidase inhibitor, clade A member 3 (SERPINA3) belongs to the serpin family with an inhibitory activity against proteases. Its aberrant expression has been observed in a wide range of tumor cells. However, its clinical significance and biological function in endometrial cancer have been rarely studied. We designed a study to determine the levels of SERPINA3 and its significance in patients with endometrial cancer.
AIM To investigate the clinical significance and role of SERPINA3 expression in endometrial cancer cells.
METHODS Eighty endometrial tissue samples collected from patients with endometrial cancer were included in an observation group and 80 paraffin-embedded tissues samples collected from patients with normal endometrial tissues undergoing myomectomy were employed as a control group between January 2014 and December 2018. The expression of SERPINA3 mRNA was detected by quantitative polymerase chain reaction (PCR) for all endometrial tissues included in the study.
RESULTS The positive expression rate of SERPINA3 protein in endometrial cancer cells was 71.25% in the observation group, which was significantly higher than that in the control group (31.25%; P < 0.05). There was no correlation between SERPINA3 protein in endometrial cancer cells and the age range at which women experienced menopause (P > 0.05). However, it was associated with pathological grade, clinical stage, vascular invasion, and lymph node metastasis (P < 0.05). Pathological grade, clinical stage, vascular invasion, and lymph node metastasis were independent prognostic factors for endometrial cancer.
CONCLUSION The follow-up study of SERPINA3 can be used as a prognostic biomarker for endometrial cancer and as one of the targets for bio-targeted therapy for endometrial cancer.
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Affiliation(s)
- Mian-Li Zhou
- Department of Gynecology and Obstetrics, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Fang-Shan Chen
- Department of Gynecology and Obstetrics, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Hui Mao
- Department of Oncology, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou 646000, Sichuan Province, China
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37
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Hu S, Yin X, Zhang G, Meng F. Identification of DNA methylation signature to predict prognosis in gastric adenocarcinoma. J Cell Biochem 2019; 120:11708-11715. [PMID: 30775802 DOI: 10.1002/jcb.28450] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 12/02/2018] [Accepted: 12/06/2018] [Indexed: 01/24/2023]
Abstract
Gastric adenocarcinoma is an important death-related cancer. To find factors related to survival and prognosis, and thus improve recovery prospects, a powerful signature is needed. DNA methylation plays an important role in gastric adenocarcinoma processes and development, and here we report on the search for a significant DNA methylation gene to aid with the earlier diagnosis of gastric adenocarcinoma patients. A Cox proportional risk regression analysis and random survival forest algorithm were used to analyze gastric adenocarcinoma patients' DNA methylation data from The Cancer Genome Atlas, a public database. DNA methylation gene signature consisting of five genes (SERPINA3, AP000357.4, GZMA, AC004702.2, and GREB1L) were selected. As the most accurate predictor, the area under the curve in the training and test group were 0.72 and 0.61, respectively. The signature was able to sort patients into high- and low-risk groups with meaningful overall survival rates (median: 18.36 vs 72.23 months, log-rank test, P < 0.001) in the training group, which predictive ability was validated in a test data set (median: 25.56 vs 58.80 months, log-rank test, P < 0.016). A multivariate Cox regression analysis showed the significant DNA methylation was an independent prediction prognostic factor for gastric adenocarcinoma patients. Functional analysis suggests that these signature genes may be related to pathways and biological processes associated with tumorigenesis. The significant DNA methylation gene could be a novel prediction and prognostic biomarker that both aids in the treatment and predicts the overall survival likelihoods of gastric adenocarcinoma patients.
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Affiliation(s)
- Sifeng Hu
- Department of General Surgery, Zoucheng People's Hospital, Zoucheng, Shandong, People's Republic of China
| | - Xiankun Yin
- Department of General Surgery, Zoucheng People's Hospital, Zoucheng, Shandong, People's Republic of China
| | - Guangyong Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China
| | - Fanmei Meng
- Department of Surgery, Zoucheng People's Hospital, Zoucheng, Shandong, People's Republic of China
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38
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Apicella C, Ruano CSM, Méhats C, Miralles F, Vaiman D. The Role of Epigenetics in Placental Development and the Etiology of Preeclampsia. Int J Mol Sci 2019; 20:ijms20112837. [PMID: 31212604 PMCID: PMC6600551 DOI: 10.3390/ijms20112837] [Citation(s) in RCA: 119] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 06/03/2019] [Accepted: 06/03/2019] [Indexed: 12/12/2022] Open
Abstract
In this review, we comprehensively present the function of epigenetic regulations in normal placental development as well as in a prominent disease of placental origin, preeclampsia (PE). We describe current progress concerning the impact of DNA methylation, non-coding RNA (with a special emphasis on long non-coding RNA (lncRNA) and microRNA (miRNA)) and more marginally histone post-translational modifications, in the processes leading to normal and abnormal placental function. We also explore the potential use of epigenetic marks circulating in the maternal blood flow as putative biomarkers able to prognosticate the onset of PE, as well as classifying it according to its severity. The correlation between epigenetic marks and impacts on gene expression is systematically evaluated for the different epigenetic marks analyzed.
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Affiliation(s)
- Clara Apicella
- Institut Cochin, U1016 INSERM, UMR8104 CNRS, Université Paris Descartes, 24 rue du faubourg St Jacques, 75014 Paris, France.
| | - Camino S M Ruano
- Institut Cochin, U1016 INSERM, UMR8104 CNRS, Université Paris Descartes, 24 rue du faubourg St Jacques, 75014 Paris, France.
| | - Céline Méhats
- Institut Cochin, U1016 INSERM, UMR8104 CNRS, Université Paris Descartes, 24 rue du faubourg St Jacques, 75014 Paris, France.
| | - Francisco Miralles
- Institut Cochin, U1016 INSERM, UMR8104 CNRS, Université Paris Descartes, 24 rue du faubourg St Jacques, 75014 Paris, France.
| | - Daniel Vaiman
- Institut Cochin, U1016 INSERM, UMR8104 CNRS, Université Paris Descartes, 24 rue du faubourg St Jacques, 75014 Paris, France.
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Differential global and MTHFR gene specific methylation patterns in preeclampsia and recurrent miscarriages: A case-control study from North India. Gene 2019; 704:68-73. [PMID: 30986448 DOI: 10.1016/j.gene.2019.04.036] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 03/23/2019] [Accepted: 04/11/2019] [Indexed: 12/15/2022]
Abstract
AIM The purpose of the present study is to evaluate and understand the association of global and MTHFR gene specific methylation in preeclampsia and recurrent miscarriages in light of MTHFR C677T polymorphism. METHODS The subjects comprised of recurrent miscarriage cases, their gestation matched controls, preeclampsia cases and matched controls. A set of women at full term were also recruited. Fasting blood sample (~5 ml) was drawn from all the participants followed by DNA extraction, global DNA methylation and MTHFR gene specific methylation. MTHFR C677T polymorphism was analysed by PCR followed by RFLP. RESULTS HIGHER Global DNA methylation at maternal front (p = 0.04) and hypomethylation of MTHFR gene at fetal front (p = 0.001) might be a characteristic of preeclampsia. Recurrent miscarriage cases were having significantly (p = 0.002) hyper MTHFR gene specific methylation as compared to controls. Women carrying CT genotype were found to be having significantly (p = 0.001) higher global DNA methylation in PE cases and MTHFR gene specific methylation (p = 0.005) in RM cases. Intergenerational analysis revealed similar patterns of global DNA methylation and MTHFR gene specific methylation among both PE and RM cases at maternal and fetal fronts. CONCLUSION The study highlights the importance of global DNA methylation in Preeclampsia and MTHFR gene specific methylation in recurrent miscarriages. MTHFR C677T gene polymorphism in association with global and gene specific methylation seem to play a pivotal role in PE and RM respectively.
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Yang SZ, He H, Zhang ZJ, Niu H, Chen FY, Wen YF, Xu JW, Dang RH, Lan XY, Lei CZ, Chen H, Huang BZ, Huang YZ. Determination of genetic effects of SERPINA3 on important growth traits in beef cattle. Anim Biotechnol 2019; 31:164-173. [PMID: 30929567 DOI: 10.1080/10495398.2018.1560306] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Serine protease inhibitor protein 3 (serpin peptidase inhibitor, clade A, member 3, SERPINA3) is a member of the serpin superfamily, probably related to the yield and quality of muscle. This study focuses on the relationship between SERPINA3 gene polymorphism and growth traits in beef cattle. The study first uses sequencing pooled DNA samples (Pool-Seq), PCR-RFLP and Tetra-primer ARMS-PCR techniques to determine the genetic polymorphisms of SERPINA3 in 765 beef cattle. Then, the polymorphic loci were correlated with the growth characters of cattle. Five SNPs (SNP1:A-648G, SNP2:T6496A, SNP3:G2495A, SNP4:T2595A, SNP5:A2615G) were found, located in the promoter, introns 5 and SNP 3, 4, 5 were in exons 2, respectively. The observed He was from 0.44 to 0.5, Ne were approaching 2 (1.78 to 2.00). The maximum and minimum PIC (polymorphism information content) values were 0.37 and 0.34, respectively. The association analysis results showed that the SNPs had a significant height in the chest girth and body length. (p < 0.05 or p < 0.01). This will provide important information for the rapid breeding of Chinese yellow cattle and the establishment of a molecular genetic marker database.
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Affiliation(s)
- Shi-Zhen Yang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Hua He
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China.,College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Zi-Jing Zhang
- Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou, Henan, People's Republic of China
| | - Hui Niu
- College of Animal Science and Technology, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, People's Republic of China
| | - Fu-Ying Chen
- Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou, Henan, People's Republic of China
| | - Yi-Fan Wen
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Jia-Wei Xu
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Rui-Hua Dang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Xian-Yong Lan
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Chu-Zhao Lei
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Hong Chen
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Bi-Zhi Huang
- Yunnan Academy of Grassland Animal Science, Xiaoshao, Kunming, People's Republic of China
| | - Yong-Zhen Huang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
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Niu P, Wei Y, Gao Q, Zhang X, Hu Y, Qiu Y, Mu Y, Li K. Male Fertility Potential Molecular Mechanisms Revealed by iTRAQ-Based Quantitative Proteomic Analysis of the Epididymis from Wip1−/− Mice. ACTA ACUST UNITED AC 2019; 23:54-66. [DOI: 10.1089/omi.2018.0155] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Pengxia Niu
- Pig Genetic Engineering and Germplasm Innovation, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yinghui Wei
- Pig Genetic Engineering and Germplasm Innovation, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Qian Gao
- Pig Genetic Engineering and Germplasm Innovation, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Xue Zhang
- Pig Genetic Engineering and Germplasm Innovation, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yanqing Hu
- Pig Genetic Engineering and Germplasm Innovation, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yiqing Qiu
- Pig Genetic Engineering and Germplasm Innovation, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yulian Mu
- Pig Genetic Engineering and Germplasm Innovation, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Kui Li
- Pig Genetic Engineering and Germplasm Innovation, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
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Wen Z, Chen Y, Long Y, Yu J, Li M. Tumor necrosis factor-alpha suppresses the invasion of HTR-8/SVneo trophoblast cells through microRNA-145-5p-mediated downregulation of Cyr61. Life Sci 2018; 209:132-139. [PMID: 30081007 DOI: 10.1016/j.lfs.2018.08.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 07/26/2018] [Accepted: 08/02/2018] [Indexed: 12/13/2022]
Abstract
Deficiency in trophoblast invasion is causally linked to the pathogenesis of preeclampsia. Tumor necrosis factor-alpha (TNF-α) shows the ability to suppress the invasiveness of trophoblasts, while cysteine-rich 61 (Cyr61) exerts an opposite function in trophoblast invasion. This study was designed to check the hypothesis that cysteine-rich 61 (Cyr61) may be involved in the anti-invasive activity of TNF-α in trophoblasts. To this end, we examined the effect of TNF-α treatment on Cyr61 expression in HTR-8/SVneo trophoblast cells and investigated the mechanism for the regulation of Cyr61 by TNF-α. Gain-of-function experiments were performed to clarify the role of Cyr61 in TNF-α-dependent suppression of trophoblast invasion. It was found that TNF-α at 1 and 10 ng/mL reduced Cyr61 protein levels by 30 and 80%, respectively, in HTR-8/SVneo cells, but did not affect the mRNA expression of Cyr61. Mechanistically, microRNA (miR)-145-5p was stimulated by TNF-α and negatively regulated the expression of Cyr61 via interaction with its 3'-untranslated region. Functionally, overexpression of miR-145-5p significantly impaired the migration and invasion of HTR-8/SVneo cells. Depletion of miR-145-5p rescued HTR-8/SVneo cells from TNF-α-mediated invasion suppression, which coincided with prevention of Cyr61 downregulation by TNF-α. In addition, overexpression of Cyr61 partially restored the invasion of HTR8/SVneo cells co-transfected with miR-145-5p mimic or exposed to TNF-α. Taken together, miR-145-5p-mediated downregulation of Cyr61 is required for the anti-invasive effect of TNF-α on trophoblasts.
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Affiliation(s)
- Zhengfang Wen
- Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, China; Departments of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China
| | - Yue Chen
- Department of Obstetrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yu Long
- Department of Obstetrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jian Yu
- Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Nanning, China
| | - Mujun Li
- Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
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43
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The proteome of fetal fluids in mares with experimentally-induced placentitis. Placenta 2018; 64:71-78. [DOI: 10.1016/j.placenta.2018.03.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 02/24/2018] [Accepted: 03/19/2018] [Indexed: 11/21/2022]
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Abstract
Preeclampsia is a major, frequent and potentially severe condition of pregnancy, characterized by severe hypertension and proteinuria. In this review, we describe recent advances in understanding the pathology, and discuss the long-term impacts on maternal vascular health. Next, we describe the genetic, epigenetic and immunological basis of preeclampsia. We describe the links between preeclampsia and oxidative stress in placental (trophoblast) and endothelial cells. We mention cellular and animal models commonly used to decipher modified pathophysiological pathways in a preeclamptic pregnancy compared to a normal pregnancy. Finally, we discuss the therapeutic options, readily available or in development, to improve the monitoring of pregnancies, the health of patients and that of children born from preeclamptic pregnancies.
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Affiliation(s)
- Céline Méhats
- Inserm U1016, CNRS UMR8104, Institut Cochin, équipe FGTB, 24, rue du faubourg Saint-Jacques, 75014 Paris, France
| | - Francisco Miralles
- Inserm U1016, CNRS UMR8104, Institut Cochin, équipe FGTB, 24, rue du faubourg Saint-Jacques, 75014 Paris, France
| | - Daniel Vaiman
- Inserm U1016, CNRS UMR8104, Institut Cochin, équipe FGTB, 24, rue du faubourg Saint-Jacques, 75014 Paris, France
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Bounds KR, Chiasson VL, Pan LJ, Gupta S, Chatterjee P. MicroRNAs: New Players in the Pathobiology of Preeclampsia. Front Cardiovasc Med 2017; 4:60. [PMID: 28993808 PMCID: PMC5622156 DOI: 10.3389/fcvm.2017.00060] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 09/06/2017] [Indexed: 12/18/2022] Open
Abstract
Our understanding of how microRNAs (miRNAs) regulate gene networks and affect different molecular pathways leading to various human pathologies has significantly improved over the years. In contrary, the role of miRNAs in pregnancy-related hypertensive disorders such as preeclampsia (PE) is only beginning to emerge. Recent papers highlight that adverse pregnancy outcomes are associated with aberrant expression of several miRNAs. Presently, efforts are underway to determine the biologic function of these placental miRNAs which can shed light on their contribution to these pregnancy-related disease conditions. The discovery that miRNAs are stable in circulation coupled with the fact that the placenta is capable of releasing them to the circulation in exosomes generates a lot of enthusiasm to use them as biomarkers. In this review, we will summarize the recent findings of our understanding of miRNA regulation in relation to PE, a hypertensive disorder of pregnancy. Particular emphasis will be given to the role of key miRNA molecules such as miR-210 and miR-155 that are known to be consistently dysregulated in women with PE.
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Affiliation(s)
- Kelsey R Bounds
- Department of Internal Medicine, Baylor Scott & White Health, Texas A&M Health Science Center, Temple, TX, United States
| | - Valorie L Chiasson
- Department of Internal Medicine, Baylor Scott & White Health, Texas A&M Health Science Center, Temple, TX, United States
| | - Lu J Pan
- Department of Internal Medicine, Baylor Scott & White Health, Texas A&M Health Science Center, Temple, TX, United States
| | - Sudhiranjan Gupta
- Department of Medical Physiology, Baylor Scott & White Health, Texas A&M Health Science Center, Temple, TX, United States
| | - Piyali Chatterjee
- Department of Internal Medicine, Baylor Scott & White Health, Texas A&M Health Science Center, Temple, TX, United States
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Luo D, Chen W, Tian Y, Li J, Xu X, Chen C, Li F. Serpin peptidase inhibitor, clade A member 3 (SERPINA3), is overexpressed in glioma and associated with poor prognosis in glioma patients. Onco Targets Ther 2017; 10:2173-2181. [PMID: 28458560 PMCID: PMC5403010 DOI: 10.2147/ott.s133022] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Glioma is the most common and aggressive human primary tumor in the central nervous system. Despite present clinical advancements, median survival time remains poor in this malignant tumor. Serpin peptidase inhibitor, clade A member 3 (SERPINA3), is a member of the serpin superfamily of protease inhibitors. Its aberrant expression has been observed in various tumors. However, its clinical significance and biological function in glioma remain unclear, especially for the prognosis of glioma patients. In this study, we investigated SERPINA3 expression in glioma tissue samples and its significance in predicting the prognosis of glioma patients. SERPINA3 protein expression was studied by immunohistochemistry, while real-time polymerase chain reaction was used to study SERPINA3 mRNA expression. We found that SERPINA3 was upregulated in glioma tissue at both mRNA and protein levels, compared with noncancerous brain tissues. We also found that high SERPINA3 expression in glioma tissues correlated significantly with advanced World Health Organization grade. Univariate and multivariate analyses revealed that high SERPINA3 expression was an independent prognostic factor for poor overall survival of glioma patients. Moreover, our findings were further validated by online Oncomine database. Taken together, our results suggest that SERPINA3 plays an oncogenic role in glioma progression and provide an insight into the application of SERPINA3 as a novel predictor of clinical outcomes and a potential biomarker of glioma.
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Affiliation(s)
- Dingyuan Luo
- Department of Vascular and Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University.,Department of Neurosurgery, Guangzhou Women and Children's Medical Center.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Wei Chen
- Department of Neurosurgery, Guangzhou Women and Children's Medical Center
| | - Yun Tian
- Department of Neurosurgery, Guangzhou Women and Children's Medical Center
| | - Junliang Li
- Department of Neurosurgery, Guangzhou Women and Children's Medical Center
| | - Xinke Xu
- Department of Neurosurgery, Guangzhou Women and Children's Medical Center
| | - Cheng Chen
- Department of Neurosurgery, Guangzhou Women and Children's Medical Center
| | - Fangcheng Li
- Department of Neurosurgery, Guangzhou Women and Children's Medical Center
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Zhang Y, He J, Zhao J, Xu M, Lou D, Tso P, Li Z, Li X. Effect of ApoA4 on SERPINA3 mediated by nuclear receptors NR4A1 and NR1D1 in hepatocytes. Biochem Biophys Res Commun 2017; 487:327-332. [PMID: 28412351 DOI: 10.1016/j.bbrc.2017.04.058] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2017] [Accepted: 04/12/2017] [Indexed: 12/29/2022]
Abstract
ApoA4 exerts anti-inflammatory effects, but the mechanism remains unclear. SERPINA3 is a member of the serine proteinase inhibitor gene family, and has been shown to be involved in anti-inflammation and associated with a number of human diseases. In this study, we revealed that ApoA4 stimulates the gene expression of SERPINA3 in mouse hepatocytes both in vivo and in vitro, in a dose- and time-dependent manner. The transcriptional response of SERPINA3 to ApoA4 is regulated through the binding of ApoA4 with nuclear receptors NR4A1 and NR1D1 on the SERPINA3 promoter, which was verified with ChIP, Luciferase activity assay and RNA interference-mediated NR4A1 or NR1D1 gene knockdown. These data suggests that ApoA4 transcriptionally induced SERPINA3 expression via NR1D1 and NR4A1. Our findings may throw light on the function of ApoA4 in inflammatory responses and acute-phase reactions, as well as the development of SERPINA3 relative diseases.
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Affiliation(s)
- Yupeng Zhang
- National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China
| | - Jing He
- College of Medicine and Forensic Science, Xi'an Jiaotong University, Xi'an, China
| | - Jing Zhao
- College of Medicine and Forensic Science, Xi'an Jiaotong University, Xi'an, China
| | - Min Xu
- Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, USA
| | - Danwen Lou
- Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, USA
| | - Patrick Tso
- Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, USA
| | - Zongfang Li
- National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China
| | - Xiaoming Li
- National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.
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Perumal N, Manicam C, Steinicke M, Funke S, Pfeiffer N, Grus FH. Characterization of the human aqueous humour proteome: A comparison of the genders. PLoS One 2017; 12:e0172481. [PMID: 28273097 PMCID: PMC5342205 DOI: 10.1371/journal.pone.0172481] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Accepted: 02/06/2017] [Indexed: 01/20/2023] Open
Abstract
Aqueous humour (AH) is an important biologic fluid that maintains normal intraocular pressure and contains proteins that regulate the homeostasis of ocular tissues. Any alterations in the protein compositions are correlated to the pathogenesis of various ocular disorders. In recent years, gender-based medicine has emerged as an important research focus considering the prevalence of certain diseases, which are higher in a particular sex. Nevertheless, the inter-gender variations in the AH proteome are unknown. Therefore, this study endeavoured to characterize the AH proteome to assess the differences between genders. Thirty AH samples of patients who underwent cataract surgery were categorized according to their gender. Label-free quantitative discovery mass spectrometry-based proteomics strategy was employed to characterize the AH proteome. A total of 147 proteins were identified with a false discovery rate of less than 1% and only the top 10 major AH proteins make up almost 90% of the total identified proteins. A large number of proteins identified were correlated to defence, immune and inflammatory mechanisms, and response to wounding. Four proteins were found to be differentially abundant between the genders, comprising SERPINF1, SERPINA3, SERPING1 and PTGDS. The findings emerging from our study provide the first insight into the gender-based proteome differences in the AH and also highlight the importance in considering potential sex-dependent changes in the proteome of ocular pathologies in future studies employing the AH.
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Affiliation(s)
- Natarajan Perumal
- Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Caroline Manicam
- Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Matthias Steinicke
- Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Sebastian Funke
- Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Norbert Pfeiffer
- Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Franz H. Grus
- Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- * E-mail:
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50
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Vaiman D. Genes, epigenetics and miRNA regulation in the placenta. Placenta 2016; 52:127-133. [PMID: 28043658 DOI: 10.1016/j.placenta.2016.12.026] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Revised: 10/24/2016] [Accepted: 12/23/2016] [Indexed: 12/19/2022]
Abstract
This text reviews briefly the context in which epigenetics regulate gene expression in trophoblast development and function. It is an attempt to focus on a limited number of recent papers that, according to the author, shed new light on placental development, and constitute possible trails for improving knowledge and women follow-up in pathological pregnancies.
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Affiliation(s)
- Daniel Vaiman
- Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris-Descartes, 24, rue du Faubourg St-Jacques, 75014, Paris, France.
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