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Cao WL, Yu CP, Zhang LL. Serum proteins differentially expressed in gestational diabetes mellitus assessed using isobaric tag for relative and absolute quantitation proteomics. World J Clin Cases 2024; 12:1395-1405. [PMID: 38576811 PMCID: PMC10989458 DOI: 10.12998/wjcc.v12.i8.1395] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 01/08/2024] [Accepted: 02/18/2024] [Indexed: 03/12/2024] Open
Abstract
BACKGROUND As a well-known fact to the public, gestational diabetes mellitus (GDM) could bring serious risks for both pregnant women and infants. During this important investigation into the linkage between GDM patients and their altered expression in the serum, proteomics techniques were deployed to detect the differentially expressed proteins (DEPs) of in the serum of GDM patients to further explore its pathogenesis, and find out possible biomarkers to forecast GDM occurrence. AIM To investigation serum proteins differentially expressed in GDM were assessed using isobaric tag for relative and absolute quantitation (iTRAQ) proteomics and bioinformatics analyses. METHODS Subjects were divided into GDM and normal control groups according to the IADPSG diagnostic criteria. Serum samples were randomly selected from four cases in each group at 24-28 wk of gestation, and the blood samples were identified by applying iTRAQ technology combined with liquid chromatography-tandem mass spectrometry. Key proteins and signaling pathways associated with GDM were identified by bioinformatics analysis, and the expression of key proteins in serum from 12 wk to 16 wk of gestation was further verified using enzyme-linked immunosorbent assay (ELISA). RESULTS Forty-seven proteins were significantly differentially expressed by analyzing the serum samples between the GDM gravidas as well as the healthy ones. Among them, 31 proteins were found to be upregulated notably and the rest 16 proteins were downregulated remarkably. Bioinformatic data report revealed abnormal expression of proteins associated with lipid metabolism, coagulation cascade activation, complement system and inflammatory response in the GDM group. ELISA results showed that the contents of RBP4, as well as ANGPTL8, increased in the serum of GDM gravidas compared with the healthy ones, and this change was found to initiate from 12 wk to 16 wk of gestation. CONCLUSION GDM symptoms may involve abnormalities in lipid metabolism, coagulation cascade activation, complement system and inflammatory response. RBP4 and ANGPTL8 are expected to be early predictors of GDM.
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Affiliation(s)
- Wei-Li Cao
- Department of Women’s Health Care, Maternal and Child Health Hospital of Hubei Province, Wuhan 430070, Hubei Province, China
| | - Cui-Ping Yu
- Obstetrical Department, The First People’s Hospital of Jiangxia District Wuhan City (Union Jiangnan Hospital Huazhong University of Science and Technology), Wuhan 430200, Hubei Province, China
| | - Ling-Li Zhang
- Department of Gynecology, Maternal and Child Health Hospital of Hubei Province, Wuhan 430070, Hubei Province, China
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Serum inter-alpha-trypsin inhibitor heavy chain 4 in patients with inflammatory bowel disease: correlation with disease risk, inflammation, activity, and its variation after treatment. Ir J Med Sci 2021; 191:2105-2111. [PMID: 34843071 DOI: 10.1007/s11845-021-02837-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 10/22/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) plays vital roles in inflammatory and auto-immune diseases, but its correlations with disease risk and clinical features in inflammatory bowel disease (IBD) need further investigation. The present study intended to explore the correlation of ITIH4 with disease activity and inflammation, as well as its change after treatment in IBD patients. METHODS Totally, 40 active Crohn's disease (A-CD) patients, 40 clinical-remission CD (R-CD) patients, 40 active ulcerative colitis (A-UC) patients, 40 clinical-remission UC (R-UC) patients, and 40 health controls (HCs) were enrolled. ITIH4 in serum was assessed by ELISA. RESULTS ITIH4 was lower in A-CD, R-CD, A-UC, and R-UC patients than in HCs (P < 0.001). Notably, ITIH4 reduced in A-CD patients than in R-CD patients (P = 0.017), and in A-UC patients compared with R-UC patients (P = 0.010). Besides, in A-CD patients, ITIH4 negatively correlated with tumor necrosis factor-alpha (TNF-α), interleukin (IL)-17A, IL-1β, C-reactive protein (CRP), and clinical disease activity index score (all P < 0.05). In A-UC patients, ITIH4 negatively correlated with TNF-α, IL-17A, IL-1β, IL-6, CRP, and Mayo score (all P < 0.05). However, in R-CD and R-UC patients, these correlations were less obvious than in A-CD and A-UC patients. ITIH4 was increased after treatment (all P < 0.05), and its expression at W12 after treatment was higher in response patients compared with no response patients in A-CD (P = 0.022) and A-UC groups (P = 0.038). CONCLUSION ITIH4 correlates with IBD susceptibility, active risk, inflammation level, and its elevation after treatment relates to clinical response in IBD patients.
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Shen L, Liao L, Chen C, Guo Y, Song D, Wang Y, Chen Y, Zhang K, Ying M, Li S, Liu Q, Ni J. Proteomics Analysis of Blood Serums from Alzheimer's Disease Patients Using iTRAQ Labeling Technology. J Alzheimers Dis 2018; 56:361-378. [PMID: 27911324 DOI: 10.3233/jad-160913] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Alzheimer' disease (AD) is the most common form of dementia affecting up to 6% of the population over the age of 65. In order to discover differentially expressed proteins that might serve as potential biomarkers, the serums from AD patients and healthy controls were compared and analyzed using the proteomics approach of isobaric tagging for relative and absolute quantitation (iTRAQ). For the first time, AD biomarkers in serums are investigated in the Han Chinese population using iTRAQ labeled proteomics strategy. Twenty-two differentially expressed proteins were identified and out of which nine proteins were further validated with more sample test. Another three proteins that have been reported in the literature to be potentially associated with AD were also investigated for alteration in expression level. Functions of those proteins were mainly related to the following processes: amyloid-β (Aβ) metabolism, cholesterol transport, complement and coagulation cascades, immune response, inflammation, hemostasis, hyaluronan metabolism, and oxidative stress. These results support current views on the molecular mechanism of AD. For the first time, differential expression of zinc-alpha-2-glycoprotein (AZGP1), fibulin-1 (FBLN1), platelet basic protein (PPBP), thrombospondin-1 (THBS1), S100 calcium-binding protein A8 (S100A8), and S100 calcium-binding protein A9 (S100A9) were detected in the serums of AD patients compared with healthy controls. These proteins might play a role in AD pathophysiology and serve as potential biomarkers for AD diagnosis. Specifically, our results strengthened the crucial role of Aβ metabolism and blood coagulation in AD pathogenesis and proteins related to these two processes may be used as peripheral blood biomarkers for AD.
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Affiliation(s)
- Liming Shen
- College of Life Science and Oceanography, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, P.R. China
| | - Liping Liao
- College of Life Science and Oceanography, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, P.R. China
| | - Cheng Chen
- College of Life Science and Oceanography, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, P.R. China
| | - Yi Guo
- Department of Neurology, Shenzhen People's Hospital, P.R. China
| | - Dalin Song
- Department of Geriatrics, Qingdao Municipal Hospital, Qingdao, P.R. China
| | - Yong Wang
- College of Life Science and Oceanography, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, P.R. China
| | - Youjiao Chen
- College of Life Science and Oceanography, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, P.R. China
| | - Kaoyuan Zhang
- College of Life Science and Oceanography, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, P.R. China
| | - Ming Ying
- College of Life Science and Oceanography, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, P.R. China
| | - Shuiming Li
- College of Life Science and Oceanography, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, P.R. China
| | - Qiong Liu
- College of Life Science and Oceanography, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, P.R. China
| | - Jiazuan Ni
- College of Life Science and Oceanography, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, P.R. China
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Zhao D, Shen L, Wei Y, Xie J, Chen S, Liang Y, Chen Y, Wu H. Identification of candidate biomarkers for the prediction of gestational diabetes mellitus in the early stages of pregnancy using iTRAQ quantitative proteomics. Proteomics Clin Appl 2017; 11. [PMID: 28220636 DOI: 10.1002/prca.201600152] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 02/08/2017] [Accepted: 02/17/2017] [Indexed: 12/16/2022]
Affiliation(s)
- Danqing Zhao
- Department of General Surgery; the Second Affiliated Hospital of Soochow University; Suzhou P. R. China
- Department of Obstetrics and Gynecology; Affiliated Hospital of Guizhou Medical University; Guiyang P. R. China
| | - Liming Shen
- College of Life Science and Oceanography; Shenzhen University; Shenzhen P. R. China
| | - Yan Wei
- School of Public Health; Guizhou Medical University; Guiyang P. R. China
| | - Jiaming Xie
- Department of General Surgery; the Second Affiliated Hospital of Soochow University; Suzhou P. R. China
| | - Shuqiang Chen
- Department of Obstetrics and Gynecology; Affiliated Hospital of Guizhou Medical University; Guiyang P. R. China
| | - Yi Liang
- Department of Obstetrics and Gynecology; Affiliated Hospital of Guizhou Medical University; Guiyang P. R. China
| | - Youjiao Chen
- College of Life Science and Oceanography; Shenzhen University; Shenzhen P. R. China
| | - Haorong Wu
- Department of General Surgery; the Second Affiliated Hospital of Soochow University; Suzhou P. R. China
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Soler L, García N, Unzueta A, Piñeiro M, Álava M, Lampreave F. Purification and determination of C-reactive protein and inter-α-trypsin inhibitor heavy chain 4 in dogs after major surgery through generation of specific antibodies. Vet Immunol Immunopathol 2016; 179:26-31. [DOI: 10.1016/j.vetimm.2016.07.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Revised: 07/12/2016] [Accepted: 07/20/2016] [Indexed: 12/12/2022]
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Muckova P, Wendler S, Rubel D, Büchler R, Alert M, Gross O, Rhode H. Preclinical Alterations in the Serum of COL(IV)A3–/– Mice as Early Biomarkers of Alport Syndrome. J Proteome Res 2015; 14:5202-14. [DOI: 10.1021/acs.jproteome.5b00814] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Petra Muckova
- Institute
of Biochemistry I, University Hospital Jena, Nonnenplan 2-4, 07740 Jena, Germany
- Clinic
of Neurology, University Hospital Jena, Erlanger Allee 101, 07740 Jena, Germany
| | - Sindy Wendler
- Institute
of Biochemistry I, University Hospital Jena, Nonnenplan 2-4, 07740 Jena, Germany
| | - Diana Rubel
- Department
of Nephrology and Rheumatology, University Medicine Göttingen, Robert-Koch Str. 40, 37075 Göttingen, Germany
| | - Rita Büchler
- Institute
of Biochemistry I, University Hospital Jena, Nonnenplan 2-4, 07740 Jena, Germany
| | - Mandy Alert
- Institute
of Biochemistry I, University Hospital Jena, Nonnenplan 2-4, 07740 Jena, Germany
| | - Oliver Gross
- Department
of Nephrology and Rheumatology, University Medicine Göttingen, Robert-Koch Str. 40, 37075 Göttingen, Germany
| | - Heidrun Rhode
- Institute
of Biochemistry I, University Hospital Jena, Nonnenplan 2-4, 07740 Jena, Germany
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ITIH family genes confer risk to schizophrenia and major depressive disorder in the Han Chinese population. Prog Neuropsychopharmacol Biol Psychiatry 2014; 51:34-8. [PMID: 24389398 DOI: 10.1016/j.pnpbp.2013.12.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2013] [Revised: 12/07/2013] [Accepted: 12/09/2013] [Indexed: 11/23/2022]
Abstract
As a major extracellular matrix component, ITIHs played an important role in inflammation and carcinogenesis. Several genome-wide association studies have reported that some positive signals which were derived from the tight linkage disequilibrium region on chromosome 3p21 were associated with both schizophrenia and bipolar disorders in the Caucasian population. To further investigate whether this genomic region is also a susceptibility locus of schizophrenia and major depressive disorder in the Han Chinese population, we conducted this study by recruiting 1235 schizophrenia patients, 1045 major depressive disorder patients and 1235 healthy control subjects in the Han Chinese samples for a case-control study. We genotyped seven SNPs within this region using TaqMan® technology. We found that rs2710322 was significantly associated with schizophrenia (adjusted P(allele) = 0.0018, adjusted P(genotype) = 0.006, OR [95% CI] = 1.278 [1.117-1.462]) while rs1042779 was weakly associated with schizophrenia (adjusted P(allele) = 0.048, OR [95% CI] = 1.164 [1.040-1.303]) and major depressive disorder (adjusted P(allele) = 0.042, OR [95% CI] = 1.178 [1.047-1.326]); it was also our finding that rs3821831 was positively associated with major depressive disorder (adjusted P(allele) = 0.003, adjusted P(genotype) = 0.006, OR [95% CI] = 1.426 [1.156-1.760]). Furthermore, no haplotype was found to be associated with schizophrenia and major depressive disorder. Via the association analysis which combines the schizophrenia and major depressive disorder cases, we also notice that rs1042779 and rs3821831 were significantly associated with combined cases (rs1042779: adjusted P(allele) = 0.012, adjusted P(genotype) = 0.018, OR [95% CI] = 1.171 [1.060-1.292]; rs3821831:adjusted P(genotype) = 0.012, OR [95% CI] = 1.193 [1.010-1.410]). Our results revealed that the shared genetic risk factors of both schizophrenia and major depressive disorder exist in ITIH family genes in the Han Chinese population.
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García-Gil FA, Fuentes-Broto L, Albendea CD, Serrano MT, Roselló-Catafau J, Lampreave F, López-Pingarrón L, Escartín J, Soria J, Garcia JJ, Fernández-Cruz L. Evaluation of Institut Georges Lopez-1 preservation solution in pig pancreas transplantation: a pilot study. Transplantation 2014; 97:901-907. [PMID: 24646772 DOI: 10.1097/tp.0000000000000050] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND Institut Georges Lopez-1 preservation solution (IGL-1) is an emerging extracellular-type electrolyte solution, low in viscosity, containing polyethylene glycol 35 as a colloid. Although IGL-1 has shown beneficial outcomes in kidney and liver preservation, this pilot study is the first to evaluate the efficacy of IGL-1 in pancreas transplantation (PT) compared with the University of Wisconsin solution (UW). METHODS Sixteen Landrace pigs underwent allogeneic PT with 16 hr of cold ischemia. Grafts were preserved with IGL-1 (n=8) or UW (n=8). No immunosuppression was administered. We analyzed graft function, the acute-phase response, and oxidative stress in the pancreatic graft monitoring membrane fluidity and lipid peroxidation. RESULTS All eight grafts with IGL-1, but only six with UW, were functioning. Graft failures with UW resulted from graft thrombosis. There were no differences between the two solutions in the number of normoglycemic days (IGL-1: 11.5 ± 6.2 versus UW: 8.5 ± 4.4 days, P=0.1357), nor in lipid peroxidation during 16-hr cold ischemia (P=0.672), or reperfusion (P=0.185), but IGL-1 prevented changes in membrane fluidity after reperfusion when compared with UW (P=0.026). CONCLUSION IGL-1 offered the same degree of safety and effectiveness as UW in our model of pig PT with 16 hr of cold ischemia.
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Affiliation(s)
- Francisco A García-Gil
- 1 Department of Surgery, University of Zaragoza, Zaragoza, Spain. 2 Department of Pharmacology and Physiology, University of Zaragoza, Zaragoza, Spain. 3 Gastroenterology and Hepatology Department, HCU Lozano Blesa, Zaragoza, Spain. 4 Experimental Hepatic Ischemia-Reperfusion Unit, Institute of Biomedical Research, Spanish National Research Council, Barcelona, Spain. 5 Department of Biochemistry and Molecular Cell Biology, University of Zaragoza, Zaragoza, Spain. 6 Department of Human Anatomy and Histology, University of Zaragoza, Zaragoza, Spain. 7 Department of Pathology, HCU Lozano Blesa, Zaragoza, Spain. 8 Department of Surgery, ICMDM, Hospital Clinic, University of Barcelona, Barcelona, Spain. 9 Address correspondence to: Prof. Francisco A. García-Gil, M.D., Ph.D., Department of Surgery, University of Zaragoza, Domingo Miral, s/n, 50009, Zaragoza, Spain
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García-Gil FA, Albendea CD, Escartín J, Lampreave F, Fuentes-Broto L, Roselló-Catafau J, López-Pingarrón L, Reiter RJ, Alvarez-Alegret R, García JJ. Melatonin prolongs graft survival of pancreas allotransplants in pigs. J Pineal Res 2011; 51:445-453. [PMID: 21718360 DOI: 10.1111/j.1600-079x.2011.00908.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Oxidative stress is involved in ischemia-reperfusion injury and allograft rejection after transplantation. We studied two well-known antioxidants, melatonin and ascorbic acid (AA), in relation to the survival of a pancreas transplantation model without immunosuppression. Forty-eight Landrace pigs were divided into three groups (n = 16 each; eight donors and eight recipients) that received melatonin, AA, or no antioxidant therapy (controls). Melatonin and AA were administered (10 mg/kg body weight) intravenously to donors and recipients during surgery and on postoperative days 1-7. The molecules were also added (5 mm) to a University of Wisconsin preservation solution during organ cold storage. Melatonin significantly delayed acute rejection and prolonged allograft survival (25.1 ± 7.7 days) compared with the controls (8.1 ± 0.8 days, P = 0.013) and the AA group (9.4 ± 1.6 days, P = 0.049). Melatonin reduced indicators of oxidative stress, malondialdehyde, and 4-hydroxyalkenals, in pancreatic samples collected during procurement, cold ischemia, and reperfusion. Melatonin also reduced serum pig-major acute-phase protein/inter-α-trypsin inhibitor heavy chain 4 (pMAP/ITIH(4)) in the early post-transplantation period. AA only partially reduced oxidative damage 30 min postreperfusion and failed to prevent pMAP/ITIH(4) elevations. These findings suggested that melatonin may be a useful therapeutic tool for organ transplantation.
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