Proteome Science[JOURNAL]
Sun
200 papers
Upregulation of S100A8 in peripheral blood mononuclear cells from patients with depression treated with SSRIs: a pilot study.
Gamboa-Sánchez C, Becerril-Villanueva E, Alvarez-Herrera S … +11 more , Leyva-Mascareño G, González-López SL, Estudillo E, Fernández-Molina AE, Elizalde-Contreras JM, Ruiz-May E, Segura-Cabrera A, Jiménez-Genchi J, Pavón L, Zamudio SR, Pérez-Sánchez G
Proteome Sci · 2023 Dec · PMID 38049858 · Full text
BACKGROUND: Major depressive disorder (MDD) affects more than 350 million people worldwide, and there is currently no laboratory test to diagnose it. This pilot study aimed to identify potential biomarkers in peripheral...
BACKGROUND: Major depressive disorder (MDD) affects more than 350 million people worldwide, and there is currently no laboratory test to diagnose it. This pilot study aimed to identify potential biomarkers in peripheral blood mononuclear cells (PBMCs) from MDD patients. METHODS: We used tandem mass tagging coupled to synchronous precursor selection (mass spectrometry) to obtain the differential proteomic profile from a pool of PBMCs from MDD patients and healthy subjects, and quantitative PCR to assess gene expression of differentially expressed proteins (DEPs) of our interest. RESULTS: We identified 247 proteins, of which 133 had a fold change ≥ 2.0 compared to healthy volunteers. Using pathway enrichment analysis, we found that some processes, such as platelet degranulation, coagulation, and the inflammatory response, are perturbed in MDD patients. The gene-disease association analysis showed that molecular alterations in PBMCs from MDD patients are associated with cerebral ischemia, vascular disease, thrombosis, acute coronary syndrome, and myocardial ischemia, in addition to other conditions such as inflammation and diabetic retinopathy. CONCLUSIONS: We confirmed by qRT-PCR that S100A8 is upregulated in PBMCs from MDD patients and thus could be an emerging biomarker of this disorder. This report lays the groundwork for future studies in a broader and more diverse population and contributes to a deeper characterization of MDD.
Systematic proteomics profiling of lysine crotonylation of the lung at Pseudoglandular and Canalicular phases in human fetus.
Wang W, Shi W, Wang Y … +7 more , Yang Y, Li P, Zeng Z, Hu W, Chen Y, Tang D, Dai Y
Proteome Sci · 2023 Dec · PMID 38041078 · Full text
Lung tissue is an important organ of the fetus, and genomic research on its development has improved our understanding of the biology of this tissue. However, the proteomic research of developing fetal lung tissue is sti...
Lung tissue is an important organ of the fetus, and genomic research on its development has improved our understanding of the biology of this tissue. However, the proteomic research of developing fetal lung tissue is still very scarce. We conducted comprehensive analysis of two developmental stages of fetal lung tissue of proteomics. It showed the developmental characteristics of lung tissue, such as the down-regulation of metabolism-related protein expression, the up-regulation of cell cycle-related proteins, and the regulation in proteins and pathways related to lung development. In addition, we also discovered some key core proteins related to lung development, and provided some key crotonylation modification sites that regulation during lung tissue development. Our comprehensive analysis of lung proteomics can provide a more comprehensive understanding of the developmental status of lung tissue, and provide a certain reference for future research and epigenetics of lung tissue.
TMT quantitative proteomics reveals key proteins relevant to microRNA-1-mediated regulation in osteoarthritis.
Jiang P, Liang D, Wang H … +8 more , Zhou R, Che X, Cong L, Li P, Wang C, Li W, Wei X, Li P
Proteome Sci · 2023 Nov · PMID 37993861 · Full text
Osteoarthritis (OA) is the second-commonest arthritis, but pathogenic and regulatory mechanisms underlying OA remain incompletely understood. Here, we aimed to identify the mechanisms associated with microRNA-1 (miR-1) t...
Osteoarthritis (OA) is the second-commonest arthritis, but pathogenic and regulatory mechanisms underlying OA remain incompletely understood. Here, we aimed to identify the mechanisms associated with microRNA-1 (miR-1) treatment of OA in rodent OA models using a proteomic approach. First, N = 18 Sprague Dawley (SD) rats underwent sham surgery (n = 6) or ACL transection (n = 12), followed at an interval of one week by randomization of the ACL transection group to intra-articular administration of either 50 µL placebo (control group) or miR-1 agomir, a mimic of endogenous miR-1 (experimental group). After allowing for eight weeks of remodeling, articular cartilage tissue was harvested and immunohistochemically stained for the presence of MMP-13. Second, N = 30 Col2a1-cre-ERT2 /GFPf1/fl -RFP-miR-1 transgenic mice were randomized to intra-articular administration of either placebo (control group, N = 15) or tamoxifen, an inducer of miR-1 expression (experimental group, N = 15), before undergoing surgical disruption of the medial meniscus (DMM) after an interval of five days. After allowing for eight weeks of remodeling, articular cartilage tissue was harvested and underwent differential proteomic analysis. Specifically, tandem mass tagging (TMT) quantitative proteomic analysis was employed to identify inter-group differentially-expressed proteins (DEP), and selected DEPs were validated using real-time quantitative polymerase chain reaction (RT-qPCR) technology. Immunohistochemically-detected MMP-13 expression was significantly lower in the experimental rat group, and proteomic analyses of mouse tissue homogenate demonstrated that of 3526 identified proteins, 345 were differentially expressed (relative up- and down-regulation) in the experimental group. Proteins Fn1, P4ha1, P4ha2, Acan, F2, Col3a1, Fga, Rps29, Rpl34, and Fgg were the *top ten most-connected proteins, implying that miR-1 may regulate an expression network involving these proteins. Of these ten proteins, three were selected for further validation by RT-qPCR: the transcript of Fn1, known to be associated with OA, exhibited relative upregulation in the experimental group, whereas the transcripts of P4ha1 and Acan exhibited relative downregulation. These proteins may thus represent key miR-1 targets during OA-regulatory mechanisms, and may provide additional insights regarding therapeutic mechanisms of miR-1 in context of OA.
Quantitative proteomics analysis reveals the key proteins related to semen quality in Niangya yaks.
Wang Y, Liu Y, Cao T … +3 more , Shi C, Ren Z, Zhao Y
Proteome Sci · 2023 Oct · PMID 37875878 · Full text
BACKGROUND: Proteins related to sperm motility and sperm morphology have an important impact on sperm function such as metabolism, motility and fertilisation etc. An understanding of the key proteins related to semen qua...
BACKGROUND: Proteins related to sperm motility and sperm morphology have an important impact on sperm function such as metabolism, motility and fertilisation etc. An understanding of the key proteins related to semen quality in Niangya yaks would help to provide support for breeding. However, the key proteins that affect semen quality in Niangya yaks remain unclear. METHODS: Herein, we applied tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC‒MS/MS) to analyze the expression levels of sperm proteins in groups of high- and low-quality semen from Niangya yaks. And fifteen differentially expressed proteins (DEPs) were randomly selected for expression level validation by parallel reaction monitoring (PRM). RESULTS: Of the 2,092 quantified proteins, 280 were identified as DEPs in the high-quality group versus the low-quality group. Gene Ontology (GO) analysis revealed that in terms of biological pathways, the DEPs were mainly involved in metabolic processes, cell transformation processes, and single organism metabolic processes. In terms of cell composition, the DEPs were mainly located in the cell membrane, organelle, molecular complex. In terms of molecular functions, the most abundant functions of the DEPs were catalytic activity, binding activity, transport activity, and enzyme regulation activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the DEPs were mainly involved in the cytokine and cytokine receptor interaction, notch signaling pathway, lysine biosynthesis, renal function-related protein and proteasome pathway. From protein-protein interaction (PPI) analysis of DEPs involved in important pathways, 6 related proteins affecting the semen quality of Niangya yaks were identified. And the results of the PRM and TMT analysis were consistent. CONCLUSIONS: The differential sperm proteomic analysis of high- and low-quality semen from Niangya yaks, revealed 6 proteins (PSMC5, PSMD8, PSMB3, HSP90AA1, UGP2 and HSPB1), were mainly concentrated in energy production and metabolism, might play important roles in semen quality, which could serve as candidates for the selection and breeding of Niangya yaks.
Label-free quantitative proteomic analysis of serum exosomes in mice with thoracic aortic aneurysm.
Xu J, Liu J, Qu Y … +5 more , Jiang L, Liang R, Li B, Li L, Jiang Y
Proteome Sci · 2023 Oct · PMID 37875866 · Full text
OBJECTIVE: Thoracic aortic aneurysm (TAA) is a cardiovascular disease with high morbidity and mortality. However, the causes and mechanisms of TAA are not fully understood. Serum exosomes from mice with TAA were used to...
OBJECTIVE: Thoracic aortic aneurysm (TAA) is a cardiovascular disease with high morbidity and mortality. However, the causes and mechanisms of TAA are not fully understood. Serum exosomes from mice with TAA were used to explore the markers associated with this disease. METHODS: C57BL/6 mice were divided into three groups and given ordinary drinking water, ordinary drinking water plus a saline osmotic pump, or drinking water containing β-aminopropionitrile (BAPN) (1 g/kg/d) plus an angiotensin II (Ang II) (1 μg/kg/min) osmotic pump. Haematoxylin and eosin staining of thoracic aortic tissues was performed. The basic characteristics of exosomes were analysed. Differentially expressed proteins (DEPs) were identified by LC‒MS/MS. Protein‒protein networks and enrichment analysis were used to explore possible molecular mechanisms. RESULTS: The present study elucidated the protein expression profile of serum exosomes in mice with TAA induced by BAPN combined with Ang II. In this work, the expression of a total of 196 proteins was significantly dysregulated in serum exosomes of mice with TAA, with 122 proteins significantly upregulated and 74 proteins markedly downregulated. Notably, Haptoglobin (Hp) and Serum amyloid p-component (Sap) identified based on the PPI network were significantly upregulated and have been strongly linked to cardiovascular disease. Interestingly, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the upregulated and downregulated proteins were involved in the complement and coagulation cascade pathways. CONCLUSIONS: This study showed that the identified DEPs have potential as biomarkers for the diagnosis of TAA and provided a more comprehensive understanding of the pathophysiological mechanisms of TAA.
Integrated proteome and malonylome analyses reveal the potential meaning of TLN1 and ACTB in end-stage renal disease.
Tan R, Li D, Hu N … +9 more , Qiu J, Zeng Z, Cai W, Zhong Y, Zhang X, Pai P, Wang K, Tang D, Dai Y
Proteome Sci · 2023 Oct · PMID 37833721 · Full text
BACKGROUND: End-stage renal disease (ESRD) is a condition that is characterized by the loss of kidney function. ESRD patients suffer from various endothelial dysfunctions, inflammation, and immune system defects. Lysine...
BACKGROUND: End-stage renal disease (ESRD) is a condition that is characterized by the loss of kidney function. ESRD patients suffer from various endothelial dysfunctions, inflammation, and immune system defects. Lysine malonylation (Kmal) is a recently discovered post-translational modification (PTM). Although Kmal has the ability to regulate a wide range of biological processes in various organisms, its specific role in ESRD is limited. METHODS: In this study, the affinity enrichment and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques have been used to create the first global proteome and malonyl proteome (malonylome) profiles of peripheral blood mononuclear cells (PBMCs) from twenty patients with ESRD and eighty-one controls. RESULTS: On analysis, 793 differentially expressed proteins (DEPs) and 12 differentially malonylated proteins (DMPs) with 16 Kmal sites were identified. The Rap1 signaling pathway and platelet activation pathway were found to be important in the development of chronic kidney disease (CKD), as were DMPs TLN1 and ACTB, as well as one malonylated site. One conserved Kmal motif was also discovered. CONCLUSIONS: These findings provided the first report on the Kmal profile in ESRD, which could be useful in understanding the potential role of lysine malonylation modification in the development of ESRD.
Effects of µ-Conotoxin GIIIB on the cellular activity of mouse skeletal musculoblast: combined transcriptome and proteome analysis.
Wu HX, He PM, Jia R
Proteome Sci · 2023 Oct · PMID 37828502 · Full text
µ-Conotoxin GIIIB (µ-CTX GIIIB) is a polypeptide containing three disulfide bridges, produced by the sea snail Conus geographus. This study was aimed to explored the cytotoxic effects of µ-CTX GIIIB on mouse skeletal mus...
µ-Conotoxin GIIIB (µ-CTX GIIIB) is a polypeptide containing three disulfide bridges, produced by the sea snail Conus geographus. This study was aimed to explored the cytotoxic effects of µ-CTX GIIIB on mouse skeletal musculoblast (Sol8). Sol8 cells were exposed to ouabain and veratridine to establish the cell injury model, and then treated with µ-CTX GIIIB. CCK-8 was adopted to evaluate the cytotoxicity of µ-CTX GIIIB. Then, proteomics and transcriptome were conducted, and the explore the differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) affected by µ-CTX GIIIB were found. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to investigate the affected signaling pathways. µ-CTX GIIIB increased the cell survival rate of injured Sol8 cells. We found and identified 1,663 DEGs and 444 DEPs influenced by µ-CTX GIIIB. 106 pairs of correlated DEGs and DEPs were selected by combining transcriptome and proteome data. The results of KEGG and GO analysis showed that µ-CTX GIIB affected the cell cycle, apoptosis, DNA damage and repair, lipid metabolism and other biological processes of Sol8 cells. µ-CTX GIIIB could affected cell cycle regulation, DNA damage repair, and activation of tumor factors, with potential carcinogenic effects. Our results provide an important basis for the study of in vitro toxicity, the mechanism of toxicity and injury prevention by µ-CTX GIIIB.
Proteomic analysis of neonatal mouse hearts shows PKA functions as a cardiomyocyte replication regulator.
Hu L, Liang M, Jiang Q … +3 more , Jie Y, Chen L, Zhang F
Proteome Sci · 2023 Oct · PMID 37821903 · Full text
The ability of the adult mammalian heart to regenerate can save the cardiac muscle from a loss of function caused by injury. Cardiomyocyte regeneration is a key aspect of research for the treatment of cardiovascular dise...
The ability of the adult mammalian heart to regenerate can save the cardiac muscle from a loss of function caused by injury. Cardiomyocyte regeneration is a key aspect of research for the treatment of cardiovascular diseases. The mouse heart shows temporary regeneration in the first week after birth; thus, the newborn mouse heart is an ideal model to study heart muscle regeneration. In this study, proteomic analysis was used to investigate the differences in protein expression in the hearts of neonatal mice at days 1 (P1 group), 4 (P4 group), and 7 (P7 group). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed changes in several groups of proteins, including the protein kinase A (PKA) signaling pathway. Moreover, it was found that PKA inhibitors and agonists regulated cardiomyocyte replication in neonatal mouse hearts. These findings suggest that PKA may be a target for the regulation of the cardiomyocyte cell cycle.
Proteomic analysis of ceftazidime and meropenem-exposed Pseudomonas aeruginosa ATCC 9027.
Ngo HL, Huynh TQ, Tran NBV … +8 more , Nguyen NHB, Tong TH, Trinh TTL, Nguyen VD, Das PP, Lim TK, Lin Q, Nguyen TTH
Proteome Sci · 2023 Sep · PMID 37770917 · Full text
BACKGROUND: Pseudomonas aeruginosa is well known for its intrinsic ability to resist a wide range of antibiotics, thus complicates treatment. Thus, understanding the response of the pathogen to antibiotics is important f...
BACKGROUND: Pseudomonas aeruginosa is well known for its intrinsic ability to resist a wide range of antibiotics, thus complicates treatment. Thus, understanding the response of the pathogen to antibiotics is important for developing new therapies. In this study, proteomic response of P. aeruginosa to the commonly used anti-pseudomonas antibiotics, ceftazidime (Caz) and meropenem (Mem) was investigated. METHODS: P. aeruginosa ATCC 9027, an antibiotic-susceptible strain, was exposed to sub-MIC values of antibiotics either Caz or Mem for 14 days to obtain E1 strains and then cultured in antibiotic-free environments for 10 days to obtain E2 strains. Proteomes of the initial and E1, E2 strains were identified and comparatively analyzed using isobaric tags for relative and absolute quantitation (iTRAQ) in cooperation with nano LC-MS/MS. Noted up and down-regulated proteins were confirmed with quantitative reverse transcriptase PCR (qRT-PCR). RESULTS: Overall, 1039 and 1041 proteins were identified in Caz and Mem-exposed strains, respectively. Upon antibiotic exposure, there were 7-10% up-regulated (Caz: 71, Mem: 85) and down-regulated (Caz: 106, Mem: 69) proteins (1.5-fold change cut-off). For both Caz and Mem, the DEPs were primarily the ones involved in metabolic process, membrane, virulence, protein synthesis, and antibiotic resistance in which proteins involved in antibiotics resistance tended to be up-regulated while proteins involved in protein synthesis and metabolic process were down-regulated. Noted proteins included beta-lactamase AmpC which was up-regulated and OprD which was down-regulated in both the antibiotic-exposed strains. Besides, biofilm formation related proteins TssC1 and Hcp1 in Caz- exposed strains and the membrane/ periplasmic proteins Azu and PagL in Mem-exposed strains were found significantly down-regulated. qRT-PCR results confirmed the expression change of AmpC, Hcp1 and OprD proteins. CONCLUSION: Exposure of Pseudomonas aeruginosa to sub-MIC values of Caz and Mem resulted in around 10% change in its proteome. Not only proteins with confirmed roles in antibiotic resistance mechanisms changed their expression but also virulence- associated proteins. Both Caz and Mem response involved up-regulation of AmpC and down-regulation of OprD. While TssC1 and Hcp1 were responsible for Caz response, Azu and PagL were more likely involved in Mem response.
Insight into the underlying molecular mechanism of dilated cardiomyopathy through integrative analysis of data mining, iTRAQ-PRM proteomics and bioinformatics.
Xiong H, Zheng Z, Zhao C … +7 more , Zhao M, Wang Q, Zhang P, Li Y, Zhu Y, Zhu S, Li J
Proteome Sci · 2023 Sep · PMID 37740197 · Full text
BACKGROUND: DCM is a common cardiomyopathy worldwide, which is characterized by ventricular dilatation and systolic dysfunction. DCM is one of the most widespread diseases contributing to sudden death and heart failure....
BACKGROUND: DCM is a common cardiomyopathy worldwide, which is characterized by ventricular dilatation and systolic dysfunction. DCM is one of the most widespread diseases contributing to sudden death and heart failure. However, our understanding of its molecular mechanisms is limited because of its etiology and underlying mechanisms. Hence, this study explored the underlying molecular mechanism of dilated cardiomyopathy through integrative analysis of data mining, iTRAQ-PRM proteomics and bioinformatics METHODS: DCM target genes were downloaded from the public databases. Next, DCM was induced in 20 rats by 8 weeks doxorubicin treatment (2.5 mg/kg/week). We applied isobaric tags for a relative and absolute quantification (iTRAQ) coupled with proteomics approach to identify differentially expressed proteins (DEPs) in myocardial tissue. After association analysis of the DEPs and the key target genes, subsequent analyses, including functional annotation, pathway enrichment, validation, were performed. RESULTS: Nine hundred thirty-five genes were identified as key target genes from public databases. Meanwhile, a total of 782 DEPs, including 348 up-regulated and 434 down-regulated proteins, were identified in our animal experiment. The functional annotation of these DEPs revealed complicated molecular mechanisms including TCA cycle, Oxidative phosphorylation, Cardiac muscle contraction. Moreover, the DEPs were analyzed for association with the key target genes screened in the public dataset. We further determined the importance of these three pathways. CONCLUSION: Our results demonstrate that TCA cycle, Oxidative phosphorylation, Cardiac muscle contraction played important roles in the detailed molecular mechanisms of DCM.
Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells.
Gao X, Qian J, Zhang Y … +3 more , Wang H, Cui J, Yang Y
Proteome Sci · 2023 Sep · PMID 37740172 · Full text
BACKGROUND: Our previous work shows that increased matrix stiffness not only alters malignant characteristics of hepatocellular carcinoma (HCC) cells, but also attenuates metformin efficacy in treating HCC cells. Here, w...
BACKGROUND: Our previous work shows that increased matrix stiffness not only alters malignant characteristics of hepatocellular carcinoma (HCC) cells, but also attenuates metformin efficacy in treating HCC cells. Here, we identified differential membrane proteins related to matrix stiffness-mediated metformin resistance for better understand therapeutic resistance of metformin in HCC. METHODS: Differential membrane proteins in HCC cells grown on different stiffness substrates before and after metformin intervention were screened and identified using isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with the liquid chromatography-tandem mass spectrometry (LC-MS/MS), then bioinformatic analysis were applied to determine candidate membrane protein and their possible signaling pathway. RESULTS: A total of 5159 proteins were identified and 354 differential membrane proteins and membrane associated proteins, which might be associated with matrix stiffness-mediated metformin resistance were discovered. Then 94 candidate membrane proteins including 21 up-regulated protein molecules and 73 down-regulated protein molecules were further obtained. Some of them such as Annexin A2 (ANXA2), Filamin-A (FLNA), Moesin (MSN), Myosin-9 (MYH9), Elongation factor 2 (eEF2), and Tax1 binding Protein 3 (TAX1BP3) were selected for further validation. Their expressions were all downregulated in HCC cells grown on different stiffness substrates after metformin intervention. More importantly, the degree of decrease was obviously weakened on the higher stiffness substrate compared with that on the lower stiffness substrate, indicating that these candidate membrane proteins might contribute to matrix stiffness-mediated metformin resistance in HCC. CONCLUSIONS: There was an obvious change in membrane proteins in matrix stiffness-mediated metformin resistance in HCC cells. Six candidate membrane proteins may reflect the response of HCC cells under high stiffness stimulation to metformin intervention, which deserve to be investigated in the future.
PRM-based quantitative proteomics analysis of altered HSP abundance in villi and decidua of patients with early missed abortion.
Chen XF, Chen XQ, Luo HL … +3 more , Xia LN, Huang SH, Chen Q
Proteome Sci · 2023 Aug · PMID 37587463 · Full text
OBJECTIVE: In this study, we aimed to identify differentially expressed heat shock protein (HSP) profiles in the villi and decidua from patients with early missed abortion (EMA). METHODS: By using high-throughput and hig...
OBJECTIVE: In this study, we aimed to identify differentially expressed heat shock protein (HSP) profiles in the villi and decidua from patients with early missed abortion (EMA). METHODS: By using high-throughput and high-precision parallel reaction monitoring (PRM)-based targeted proteomics techniques, this study examined the abundance of HSPs in the villi and decidua of 10 patients with EMA and 10 controls. Moreover, the abundance of 3 HSPs in the villi of another 22 patients with EMA and 22 controls was verified with Western blotting and immunohistochemistry (IHC). RESULTS: There were potential differences in the abundance of 16 HSPs and 42 polypeptides in human villi and decidua compared with those of the control group. Among them, HSP90AB1, HSPD1 and HSPA13 were downregulated in abundance in villi of patients with EMA, with a statistically significant difference, which was consistent with the verification results of Western blots and IHC. CONCLUSION: Using a PRM-based targeted proteomics technique, this study is the first to screen and quantitatively analyze the expression profile of HSPs in the villi and decidua of patients with EMA. The significant downregulation of HSP90AB1, HSPD1 and HSPA13 was found to have a potentially intimate association with the occurrence of EMA. The findings in our study may provide novel potential research targets related to HSPs for the pathogenesis, prevention and treatment of EMA.
Serum proteomic identification and validation of two novel atherosclerotic aortic aneurysm biomarkers, profilin 1 and complement factor D.
Murakami Y, Nishigori M, Yagi H … +11 more , Osaki T, Wakabayashi M, Shirai M, Son C, Iba Y, Minatoya K, Kusano K, Tomita T, Ishibashi-Ueda H, Matsuda H, Minamino N
Proteome Sci · 2023 Aug · PMID 37543598 · Full text
BACKGROUND: Effective diagnostic biomarkers for aortic aneurysm (AA) that are detectable in blood tests are required because early detection and rupture risk assessment of AA can provide insights into medical therapy and...
BACKGROUND: Effective diagnostic biomarkers for aortic aneurysm (AA) that are detectable in blood tests are required because early detection and rupture risk assessment of AA can provide insights into medical therapy and preventive treatments. However, known biomarkers for AA lack specificity and reliability for clinical diagnosis. METHODS: We performed proteome analysis of serum samples from patients with atherosclerotic thoracic AA (TAA) and healthy control (HC) subjects to identify diagnostic biomarkers for AA. Serum samples were separated into low-density lipoprotein, high-density lipoprotein, and protein fractions, and the major proteins were depleted. From the proteins identified in the three fractions, we narrowed down biomarker candidates to proteins uniformly altered in all fractions between patients with TAA and HC subjects and evaluated their capability to discriminate patients with TAA and those with abdominal AA (AAA) from HC subjects using receiver operating characteristic (ROC) analysis. For the clinical validation, serum concentrations of biomarker candidates were measured in patients with TAA and AAA registered in the biobank of the same institute, and their capability for the diagnosis was evaluated. RESULTS: Profilin 1 (PFN1) and complement factor D (CFD) showed the most contrasting profiles in all three fractions between patients with TAA and HC subjects and were selected as biomarker candidates. The PFN1 concentration decreased, whereas the CFD concentration increased in the sera of patients with TAA and AAA when compared with those of HC subjects. The ROC analysis showed that these proteins could discriminate patients with TAA and AAA from HC subjects. In the validation study, these candidates showed significant concentration differences between patients with TAA or AAA and controls. PFN1 and CFD showed sufficient area under the curve (AUC) in the ROC analysis, and their combination further increased the AUC. The serum concentrations of PFN1 and CFD also showed significant differences between patients with aortic dissection and controls in the validation study. CONCLUSION: PFN1 and CFD are potential diagnostic biomarkers for TAA and AAA and measurable in blood samples; their diagnostic performance can be augmented by their combination. These biomarkers may facilitate the development of diagnostic systems to identify patients with AA.
Altered levels of transthyretin in human cerebral microdialysate after subarachnoid haemorrhage using proteomics; a descriptive pilot study.
Ginstman F, Ghafouri B, Zsigmond P
Proteome Sci · 2023 Jul · PMID 37420193 · Full text
BACKGROUND: Subarachnoid haemorrhage (SAH) is one of the most severe forms of stroke in which delayed cerebral ischemia is one of the major complications. Neurointensive care aims at preventing and treating such complica...
BACKGROUND: Subarachnoid haemorrhage (SAH) is one of the most severe forms of stroke in which delayed cerebral ischemia is one of the major complications. Neurointensive care aims at preventing and treating such complications and identification of biomarkers of early signs of ischemia might therefore be helpful. METHODS: We aimed at describing proteome profile in cerebral microdialysate in four patients with aneurysmal SAH using two dimensional gel electrophoresis in combination with mass spectrometry in search for new biomarkers for delayed cerebral ischemia and to investigate if there were temporal fluctuations in those biomarkers over time after aneurysmal bleed. RESULTS: The results showed transthyretin in nine different proteoforms (1001, 1102, 2101, 3101, 4101, 4102, 5001, 5101, 6101) in cerebral microdialysate samples from four patients having sustained SAH. Several proteoforms show highly differing levels and pooled analysis of all samples showed varying optical density related to time from aneurysmal bleed, indicating a temporal evolution. CONCLUSIONS: Transthyretin proteoforms have not earlier been shown in cerebral microdialysate after SAH and we describe differing levels based on proteoform as well as time from subarachnoid bleed. Transthyretin is well known to be synthetized in choroid plexus, whilst intraparenchymal synthesis remains controversial. The results need to be confirmed in larger studies in order to further describe transthyretin.
Data-independent acquisition-based mass spectrometry(DIA-MS) for quantitative analysis of patients with chronic hepatitis B.
Wang B, Zhang Q, Wu L … +8 more , Deng C, Luo M, Xie Y, Wu G, Chen W, Sheng Y, Zhu P, Qin G
Proteome Sci · 2023 Jun · PMID 37280603 · Full text
Chronic hepatitis B is a significant public health problem and complex pathologic process, and unraveling the underlying mechanisms and pathophysiology is of great significance. Data independent acquisition mass spectrom...
Chronic hepatitis B is a significant public health problem and complex pathologic process, and unraveling the underlying mechanisms and pathophysiology is of great significance. Data independent acquisition mass spectrometry (DIA-MS) is a label-free quantitative proteomics method that has been successfully applied to the study of a wide range of diseases. The aim of this study was to apply DIA-MS for proteomic analysis of patients with chronic hepatitis B. We performed comprehensive proteomics analysis of protein expression in serum samples from HBV patients and healthy controls by using DIA-MS. Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and protein network analysis were performed on differentially expressed proteins and were further combined with literature analysis. We successfully identified a total of 3786 serum proteins with a high quantitative performance from serum samples in this study. We identified 310 differentially expressed proteins (DEPs) (fold change > 1.5 and P value < 0.05 as the criteria for a significant difference) between HBV and healthy samples. A total of 242 upregulated proteins and 68 downregulated proteins were among the DEPs. Some protein expression levels were significantly elevated or decreased in patients with chronic hepatitis B, indicating a relation to chronic liver disease, which should be further investigated.
Purification and proteomic analysis of potent fibrinolytic enzymes extracted from Lumbricus rubellus.
Stephani L, Rahayu P, Retnoningrum D … +3 more , Suhartono MT, Rachmawati H, Tjandrawinata RR
Proteome Sci · 2023 May · PMID 37158880 · Full text
BACKGROUND: Lumbrokinase derived from earthworms, Lumbricus rubellus is known to have fibrinolytic enzymes that have potential as therapeutic drugs due to its ability to dissolve fibrin. The current study is aimed to pur...
BACKGROUND: Lumbrokinase derived from earthworms, Lumbricus rubellus is known to have fibrinolytic enzymes that have potential as therapeutic drugs due to its ability to dissolve fibrin. The current study is aimed to purify the Lumbrokinase from L. rubellus and identify its protein component. METHODS: Water extract of local earthworm Lumbricus rubellus revealed several proteins. Therefore, to identify its protein component, purification through HiPrep DEAE fast flow and proteomic analysis were conducted prior to identifications. A combination of two-dimension gel electrophoresis (2DE) and electrospray ionization mass spectrometry analysis was used to identify the purified fractions. RESULTS: The purified fractions contain five protein bands, namely F25-1, F25-2, F85-1, F85-2, and F85-3, which displayed strong fibrinogenolytic activity. F25 fractions showed fibrinogenolytic activity of 974.85 U/mg, while F85 fractions showed higher activity of 1,484.11 U/mg. Fractions F85-1, F85-2, and F85-3 showed molecular weights of 42.6 kDa, 27.03 kDa, and 14 kDa, respectively and were identified as Lumbrokinase iso-enzymes. CONCLUSION: This preliminary study indicates that the F25 and F85 fractions are similar to published fibrinolytic protease-1 and lumbrokinase, respectively, in terms of their amino acid sequence.
Proteomics identifies differentially expressed proteins in glioblastoma U87 cells treated with hederagenin.
Zhang Y, Han Y, Shang Y … +2 more , Wang X, Sun J
Proteome Sci · 2023 Apr · PMID 37120556 · Full text
OBJECTIVE: We investigated differentially expressed proteins (DEPs) in human glioblastoma U87 cells after treatment with hederagenin as a therapeutic screening mechanism and provided a theoretical basis for hederagenin i...
OBJECTIVE: We investigated differentially expressed proteins (DEPs) in human glioblastoma U87 cells after treatment with hederagenin as a therapeutic screening mechanism and provided a theoretical basis for hederagenin in treating glioblastoma. METHODS: The Cell Counting Kit 8 assay was used to analyze the inhibitory effect of hederagenin on the proliferation of U87 cells. Protein was identified by tandem mass tags and LC-MS/MS analysis techniques. Annotation of DEPs, Gene Ontology enrichment and function, and Kyoto Encyclopedia of Genes and Genomes pathways and domains were all examined by bioinformatics. According to the TMT results, hub protein was selected from DEPs for WB verification. RESULTS: Protein quantitative analysis found 6522 proteins in total. Compared with the control group, 43 DEPs (P < 0.05) were involved in the highly enriched signaling pathway in the hederagenin group, among which 20 proteins were upregulated, and 23 proteins were downregulated. These different proteins are mainly involved in the longness regulating pathway-WORM, the hedgehog signaling pathway, Staphylococcus aureus infection, complement, coagulation cascades, and mineral absorption. KIF7 and ATAD2B expression were significantly down-regulated and PHEX and TIMM9 expression were significantly upregulated, according to WB analysis, supporting the TMT findings. CONCLUSION: Hederagenin inhibition of GBM U87 cells may be related to KIF7, which is mainly involved in the hedgehog signaling pathway. Our findings lay a foundation for additional study of the therapeutic mechanism of hederagenin.
Proteomics profiling for the global and acetylated proteins of papillary thyroid cancers.
Wei W, Wu Y, Chen DD … +4 more , Song Y, Xu G, Shi Q, Dong XP
Proteome Sci · 2023 Apr · PMID 37101287 · Full text
BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy cancer among the malignancies of thyroid. Despite of wide usages of proteomics in PTC, the profile of acetylated proteins in PTC remai...
BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy cancer among the malignancies of thyroid. Despite of wide usages of proteomics in PTC, the profile of acetylated proteins in PTC remains unsettled, which is helpful for understanding the carcinogenesis mechanism and identifying useful biomarkers for PTC. METHODS: The surgically removed specimens of cancer tissues (Ca-T) and adjacent normal tissues (Ca-N) from 10 female patients pathological diagnosed as PTC (TNM stage III) were enrolled in the study. After preparing the pooled extracts of the whole proteins and the acetylated proteins from 10 cases, TMT labeling and LC/MS/MS methods were applied to the assays of global proteomics and acetylated proteomics separately. Bioinformatics analysis, including KEGG, gene ontology (GO) and hierarchical clustering were performed. Some differentially expressed proteins (DEPs) and differentially expressed acetylated proteins (DEAPs) were validated by individual Western blots. RESULTS: Controlled with the normal tissues adjacent to the lesions, 147 out of 1923 identified proteins in tumor tissues were considered as DEPs in global proteomics, including 78 up-regulated and 69 down-regulated ones, while 57 out of 311 identified acetylated proteins in tumor tissues were DEAPs in acetylated proteomics, including 32 up-regulated and 25 down-regulated, respectively. The top 3 up- and down-regulated DEPs were fibronectin 1, KRT1B protein and chitinase-3-like protein 1, as well as keratin, type I cytoskeletal 16, A-gamma globin Osilo variant and Huntingtin interacting protein-1. The top 3 up- and down-regulated DEAPs were ribosomal protein L18a-like protein, alpha-1-acid glycoprotein 2 and eukaryotic peptide chain release factor GTP-binding subunit ERF3A, as well as trefoil factor 3, thyroglobulin and histone H2B. Functional GO annotation and KEGG pathway analysis based on the DEPs and DEAPs showed completely different changing pictures. Contrary to the top 10 up- and -down regulated DEPs, most of which were addressed in PTC and other types of carcinomas, changes of the majority DEAPs were not mentioned in the literatures. CONCLUSIONS: Taken the profiling of the global and acetylated proteomics together will provide more broad view of protein alterations on the carcinogenesis and new direction for selecting biomarker for diagnosis of PTC.
Effects of Atractylodes lancea extracts on intestinal flora and serum metabolites in mice with intestinal dysbacteriosis.
Zhang B, Bu L, Tian H … +9 more , You Z, Zhao M, Tian J, Zhang Y, Wang Q, Tan C, Cao Y, Feng D, Xi Z
Proteome Sci · 2023 Apr · PMID 37061727 · Full text
OBJECTIVE: This study aims to explore the effect of an extract of Atractylodes lancea (A. lancea) on antibiotics-induced intestinal tract disorder and the probable therapeutic mechanisms employed by this extract to ameli...
OBJECTIVE: This study aims to explore the effect of an extract of Atractylodes lancea (A. lancea) on antibiotics-induced intestinal tract disorder and the probable therapeutic mechanisms employed by this extract to ameliorate these disorders. METHODS: Three days after acclimatization, nine male and nine female specific-pathogen-free (SPF) mice were randomly assigned into three groups: Group C (normal saline), Group M (antibiotic: cefradine + gentamicin), and Group T (antibiotic + A. lancea extract). Each mouse in Groups M and T received intragastric (i.g.) gavage antibiotics containing cefradine and gentamicin sulfate (0.02 ml/g/D) for 7 days. A. lancea extract (0.02 ml/g/D) was administered by i.g. gavage to Group T mice for 7 days following the cessation of antibiotic therapy. Group M received an equivalent volume of normal saline for 7 days, while Group C received an equivalent volume of normal saline for 14 days. Afterwards, we collected mouse feces to assess changes in intestinal microbiota by 16S ribosomal ribonucleic acid (rRNA) sequencing and metabolomics. In addition, serum samples were gathered and analyzed using liquid chromatography-mass spectrometry (LS-MS). Finally, we performed a correlation analysis between intestinal microbiota and metabolites. RESULTS: After treatment with antibiotic, the richness and diversity of the flora, numbers of wall-breaking bacteria and Bacteroidetes, and the numbers of beneficial bacteria decreased, while the numbers of harmful bacteria increased. After i.g. administration of A. lancea extract, the imbalance of microbial flora began to recover. Antibiotics primarily influence the metabolism of lipids, steroids, peptides, organic acids, and carbohydrates, with lipid compounds ranking first. Arachidonic acid (AA), arginine, and proline have relatively strong effects on the metabolisms of antibiotic-stressed mice. Our findings revealed that A. lancea extract might restore the metabolism of AA and L-methionine. The content of differential metabolites detected in the serum of Group T mice was comparable to that in the serum of Group C mice, but significantly different from that of Group M mice. Compared to putative biomarkers in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, it was found that altered metabolites, such as amino acids, glycerol, and phospholipids, were primarily associated with the metabolism. CONCLUSIONS: The effective mechanisms of A. lancea extract in regulating the disorder of intestinal flora in mice are related to the mechanisms of A. lancea. It could relate to lipid metabolism, bile acid metabolism, and amino acid metabolism. These results will provide a basis for further explaining the mechanism by which A. lancea regulats intestinal flora.
Proteomics analysis of methionine enkephalin upregulated macrophages against infection by the influenza-A virus.
Fu W, Xie Z, Bai M … +3 more , Zhang Z, Zhao Y, Tian J
Proteome Sci · 2023 Apr · PMID 37041527 · Full text
Macrophages have a vital role in phagocytosis and antiviral effect against invading influenza viruses. Previously, we found that methionine enkephalin (MENK) inhibited influenza virus infection by upregulating the "antiv...
Macrophages have a vital role in phagocytosis and antiviral effect against invading influenza viruses. Previously, we found that methionine enkephalin (MENK) inhibited influenza virus infection by upregulating the "antiviral state" of macrophages. To investigate the immunoregulatory mechanism of action of MENK on macrophages, we employed proteomic analysis to identify differentially expressed proteins (DEPs) between macrophages infected with the influenza-A virus and cells infected with the influenza-A virus after pretreatment with MENK. A total of 215 DEPs were identified: 164 proteins had upregulated expression and 51 proteins had downregulated expression. Proteomics analysis showed that DEPs were highly enriched in "cytokine-cytokine receptor interaction", "phagosome", and "complement and coagulation cascades pathway". Proteomics analysis revealed that MENK could be an immune modulator or prophylactic for the prevention and treatment of influenza. MENK promoted the polarization of M1 macrophages, activated inflammatory responses, and enhanced phagocytosis and killing function by upregulating opsonizing receptors.
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