Publications by authors named "Shuiming Li"

43 Publications

Global effects of RAB3GAP1 dysexpression on the proteome of mouse cortical neurons.

Amino Acids 2021 Sep 7;53(9):1339-1350. Epub 2021 Aug 7.

Institute of Neuroscience, Basic Medical College, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.

Mounting studies have demonstrated that RAB3GAP1 expression is modified in brain diseases with multiple neurobiological functions and processes and acts as a potentially significant target. However, the cellular and molecular events arising from RAB3GAP1 dysexpression are still incompletely understood. In this work, underexpression and overexpression of RAB3GAP1 were first induced into cultured mouse cortical neurons by transfection with lentivirus plasmids. Then we globally explored the effects of RAB3GAP1 dysexpression on the proteome of the neurons through the use of isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative proteomics with bioinformatics. A total of 364 proteins in the RAB3GAP1-underexpression group and 314 proteins in the RAB3GAP1-overexpression group were identified to be differentially expressed. Subsequent bioinformatics analysis indicated that the proteome functional expression profiles induced by RAB3GAP1 underexpression and overexpression were different, suggesting the potential differences in biological processes and cellular effects. Subsequent intergroup cross-comparison revealed some candidate target proteins regulated directly by RAB3GAP1. Further parallel reaction monitoring (PRM) analysis illustrated that Sub1, Ssrp1, and Top1 proteins might serve as new potentially important linkers in the RAB3GAP1-mediated autophagy pathway in the cortical neurons. Collectively, the current proteomics data furnished new valuable insights to better understand the regulatory molecular mechanism of neuronal RAB3GAP1.
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http://dx.doi.org/10.1007/s00726-021-03058-9DOI Listing
September 2021

Identification of potential allergens in larva, pupa, moth, silk, slough and feces of domestic silkworm (Bombyx mori).

Food Chem 2021 Nov 28;362:130231. Epub 2021 May 28.

School of Public Health, Health Science Center, Shenzhen University, Shenzhen 518060, Guangdong Province, PR China. Electronic address:

The silkworm (Bombyx mori) is an important economic insect that can be used as food in many countries in Asia. However, silkworms and their metabolites are an important source of allergens, which can induce severe allergic reactions. So far, there are no systematic studies on the potential allergens in silkworm and its metabolites. These studies have important guiding significance for the prevention, diagnosis, and treatment of silkworm allergy. The aim of this study was to identify the potential allergens from larva, pupa, moth, silk, slough and feces of silkworm and analyze the sequence homology of silkworm allergens with other allergens identified in the Allergenonline database. We have found 45 potential allergens in silkworm. The results of the homology comparison suggested that silkworm allergens likely cross-react with those of Dermatophagoides farinae, Aedes aegypti, Tyrophagus putrescentiae, Triticum aestivum and Malassezia furfur.
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http://dx.doi.org/10.1016/j.foodchem.2021.130231DOI Listing
November 2021

Macrophage-stimulating activity of European eel (Anguilla anguilla) peptides in RAW264.7 cells mediated via NF-κB and MAPK signaling pathways.

Food Funct 2020 Dec 7;11(12):10968-10978. Epub 2020 Dec 7.

Shenzhen Key Laboratory of Marine Bioresources and Ecology, Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, PR China.

European eel (Anguilla anguilla) is considered to be a vital commercial fish species. In this study, the effect and molecular mechanism of bioactive peptides from European eel on macrophage-stimulating activity in RAW264.7 cells were investigated. Eel peptide (EP) markedly induced NO and iNOS production and promoted TNF-α and IL-6 secretion in a concentration-dependent manner. Moreover, EP dose-dependently activated NF-κB and MAPK signaling pathways in RAW264.7 cells. In addition, EP was purified using a Sephadex A-25 column and a Bio-Gel P-6 column, and the fraction (Fr-1-1) showing the strongest NO-inducing activity was obtained. Then, the molecular weights of the components in Fr-1-1 were analyzed by LC-MS/MS and found to range from 700 to 1900 Da for the majority of components, which suggested that Fr-1-1 mainly consisted of peptides containing 8-20 amino acid residues. Overall, our results indicated that EP from Anguilla anguilla activated macrophages and could be used as a potential nutraceutical or pharmaceutical.
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http://dx.doi.org/10.1039/d0fo02497jDOI Listing
December 2020

Proteomic Analysis of Serum Differentially Expressed Proteins Between Allergic Bronchopulmonary Aspergillosis and Asthma.

Mycopathologia 2021 Mar 12;186(1):1-13. Epub 2020 Nov 12.

Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.

Background: Allergic bronchopulmonary aspergillosis (ABPA) constantly develops in asthmatics, which has not been fully investigated.

Objectives: This study aimed to investigate serum differentially expressed proteins (DEPs) between ABPA and asthma using the new approach isobaric tags by relative and absolute quantitation (iTRAQ).

Methods: Each 16 serum samples from ABPA or asthmatic subjects were pooled and screened using iTRAQ. After bioinformatic analysis, five candidate DEPs were validated in the enlarged serum samples from additional 21 ABPA, 31 asthmatic and 20 healthy subjects using ELISA. A receiver operating characteristic (ROC) curve was used to estimate the diagnostic power of carnosine dipeptidase 1 (CNDP1).

Results: A total of 29 DEPs were screened out between ABPA and asthmatic groups. Over half of them were enriched in proteolysis and regulation of protein metabolic process. Further verification showed serum levels of immunoglobulin heavy constant gamma 1, α-1-acid glycoprotein 1, corticosteroid-binding globulin and vitronectin were neither differentially altered between ABPA and asthma nor consistent with the proteomic analysis. Only serum CNDP1 was significantly decreased in ABPA patients, compared with asthmatics and healthy controls (P < 0.01 and P < 0.05). The ROC analysis determined 10.73 ng/mL as the cutoff value of CNDP1, which could distinguish ABPA among asthmatics (AUC 0.770, 95%CI 0.632-0.875, P < 0.001).

Conclusions: This study firstly identified serological DEPs between ABPA and asthma using the new technique iTRAQ. Serum CNDP1 might assist the differential diagnosis of ABPA from asthma and serve as a new pathogenetic factor in fungal colonization and sensitization.
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http://dx.doi.org/10.1007/s11046-020-00506-0DOI Listing
March 2021

Selective Covalent Targeting of Anti-apoptotic BFL-1 by a Sulfonium-Tethered Peptide.

Chembiochem 2021 01 1;22(2):340-344. Epub 2020 Oct 1.

State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Room 301, Building E, Xili University, Shenzhen, P. R. China.

Anti-apoptotic B cell lymphoma 2 (BCL-2) family proteins are proven targets for human cancers. Targeting the BH3-binding pockets of these anti-apoptotic proteins could reactivate apoptosis in BCL-2-depedent cancers. BFL-1 is a BCL-2 family protein overexpressed in various chemoresistant cancers. A unique cysteine at the binding interface of the BH3 and BFL-1 was previously proven to be an intriguing targeting site to irreversibly inhibit BFL-1 functions with stabilized cyclic peptide bearing a covalent warhead. Recently, we developed a sulfonium-tethered peptide cyclization strategy to construct peptide ligands that could selectively and efficiently react with the cysteine(s) of target proteins near the interacting interface. Using this method, we constructed a BFL-1 peptide inhibitor, B4-MC, that could selectively conjugate with BFL-1 both in vitro and in cell. B4-MC showed good cellular uptake, colocalized with BFL-1 on mitochondria, and showed obvious growth inhibition of BFL-1 over-expressed cancer cell lines.
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http://dx.doi.org/10.1002/cbic.202000473DOI Listing
January 2021

Covalent conjugation with (-)-epigallo-catechin 3-gallate and chlorogenic acid changes allergenicity and functional properties of Ara h1 from peanut.

Food Chem 2020 Nov 18;331:127355. Epub 2020 Jun 18.

School of Public Health, Health Science Center, Shenzhen University, Shenzhen, Guangdong Province 518060, PR China. Electronic address:

Ara h1 is a major allergen from peanut. We investigated the effect of covalent conjugation of Ara h1 and dietary polyphenols on allergenicity and functional properties of Ara h1. Enzyme-linked immunosorbent assay revealed that the covalent conjugation of dietary polyphenols significantly reduced the IgE binding capacity of Ara h1. Covalent binding of dietary polyphenols with Ara h1 reduced histamine release by 40% in basophils. The decreased IgE binding capacity of Ara h1 could be ascribed to changes in protein conformation. The IgE epitope of Ara h1 might be blocked by polyphenols at the binding site. Analysis of pepsin digestion of Ara h1-polyphenol conjugates indicated that the covalent binding increased pepsin digestibility and reduced IgE binding capacity. Furthermore, covalent conjugation of Ara h1 with polyphenols decreased denaturation temperature and increased antioxidant activity. Ara h1 conjugated with polyphenols may be a promising approach for reducing the allergenicity of Ara h1.
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http://dx.doi.org/10.1016/j.foodchem.2020.127355DOI Listing
November 2020

Intramolecular methionine alkylation constructs sulfonium tethered peptides for protein conjugation.

Chem Commun (Camb) 2020 Apr 3;56(26):3741-3744. Epub 2020 Mar 3.

State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, P. R. China.

Continuous efforts have been invested in the selective modification of proteins. Herein, we first report the construction of sulfonium tethered cyclic peptides via an intramolecular cyclization by an aliphatic halide. This cyclization could enhance the stability and cellular uptake of peptides. Furthermore, the sulfonium center could be recognized by cysteine in the vicinity of the protein-peptide interacting interface and form a peptide-protein conjugate.
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http://dx.doi.org/10.1039/d0cc00377hDOI Listing
April 2020

Hippocampal proteomic changes of susceptibility and resilience to depression or anxiety in a rat model of chronic mild stress.

Transl Psychiatry 2019 10 17;9(1):260. Epub 2019 Oct 17.

Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 400016, China.

Chronic stressful occurrences are documented as a vital cause of both depression and anxiety disorders. However, the stress-induced molecular mechanisms underlying the common and distinct pathophysiology of these disorders remains largely unclear. We utilized a chronic mild stress (CMS) rat model to differentiate and subgroup depression-susceptible, anxiety-susceptible, and insusceptible rats. The hippocampus was analyzed for differential proteomes by combining mass spectrometry and the isobaric tags for relative and absolute quantitation (iTRAQ) labeling technique. Out of 2593 quantified proteins, 367 were aberrantly expressed. These hippocampal protein candidates might be associated with susceptibility to stress-induced depression or anxiety and stress resilience. They provide the potential protein systems involved in various metabolic pathways as novel investigative protein targets. Further, independent immunoblot analysis identified changes in Por, Idh2 and Esd; Glo1, G6pdx, Aldh2, and Dld; Dlat, Ogdhl, Anxal, Tpp2, and Sdha that were specifically associated to depression-susceptible, anxiety-susceptible, or insusceptible groups respectively, suggesting that identical CMS differently impacted the mitochondrial and metabolic processes in the hippocampus. Collectively, the observed alterations to protein abundance profiles of the hippocampus provided significant and novel insights into the stress regulation mechanism in a CMS rat model. This might serve as the molecular basis for further studies that would contributed to a better understanding of the similarities and differences in pathophysiologic mechanisms underlying stress-induced depression or anxiety, and stress resiliency.
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http://dx.doi.org/10.1038/s41398-019-0605-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797788PMC
October 2019

Role of in the Production of Spores and Insecticidal Crystal Proteins in .

Front Microbiol 2019 4;10:2059. Epub 2019 Sep 4.

State Key Laboratory of Developmental Biology of Freshwater Fish, Hunan Provincial Key Laboratory of Microbial Molecular Biology, College of Life Science, Hunan Normal University, Changsha, China.

The small heat shock protein plays an important role in response to stresses. We wanted to investigate how Hsp20 affects sporulation and production of insecticidal crystal proteins (ICPs) in (Bt) at the stationary growth phase when cells are starved. The gene was knocked out in Bt4.0718 (wide type), which is a strain screened in our laboratory, using endonuclease I-SceI mediated unmarked gene replacement method. Deletion of Hsp20 resulted in a decrease in both sporulation and ICPs production. Bt4-Δ cells and its ICP did not have a significant difference in shape and size but entered the decline phase 2 h earlier than the Bt4.0718. In order to find the mechanism that underlies these phenotypes, we completed a proteomic study of differentially expressed proteins (DEPs). In Bt4-Δ cells, 11 DEPs were upregulated and 184 DEPs downregulated. These affected DEPs are involved in multiple metabolic pathways: (1) six DEPs (two upregulated and four downregulated) are directly related to the sporulation and ICPs synthesis; (2) supply of amino acids including amino acid synthesis and protein recycling; (3) the energy supplementation (the tricarboxylic acid cycle and glycolysis); (4) purine metabolism and mRNA stability. These results suggest that may be critical in maintaining the homeostasis of during the production of spores and ICPs, and could provide new sight into the sporulation and ICPs formation in .
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http://dx.doi.org/10.3389/fmicb.2019.02059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737285PMC
September 2019

Molecular and antimicrobial characterization of a group G anti-lipopolysaccharide factor (ALF) from Penaeus monodon.

Fish Shellfish Immunol 2019 Nov 26;94:149-156. Epub 2019 Aug 26.

Guangdong Technology Research Center for Marine Algal Bioengineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518060, PR China; Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518060, PR China. Electronic address:

Anti-lipopolysaccharide factors (ALFs) are important host-defense molecules of crustaceans. They all contain a lipopolysaccharide-binding domain (LBD) and some ALFs exhibit strong antimicrobial activity. In this research, a Group G ALF from Penaeus monodon (ALFPm11) was studied. It is an anionic peptide specifically having a cationic and highly amphipathic LBD, with five positively charged residues separated by aromatic residues. It was abundantly expressed in the hepatopancreas of P. monodon normally but the expression level in other tissues was relatively low or undetectable. However, in the shrimps challenged by Vibrio, expression of ALFPm11 could be detected in all tissues. Chemically synthesized ALFPm11-LBD displayed high inhibitory activity (minimum inhibition concentration≤ 4 μM) against various bacteria, e.g. Exiguobacterium sp. L33, Bacillus sp. T2, and Acinetobacter sp. L32. It also displayed apparent activity in the agar well diffusion assay. Furthermore, it could efficiently induce agglutination of both Gram-positive and Gram-negative bacteria and cause significant membrane permeabilization of the bacteria. As a comparative study, ALFPm11-LBD showed a better or equal antimicrobial function to ALFPm3-LBD which was reported to possess strong antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi. Thus, this research found a new effective ALF in P. monodon and demonstrated its antimicrobial mechanism, suggesting its potential applications in the future.
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http://dx.doi.org/10.1016/j.fsi.2019.08.066DOI Listing
November 2019

A sulfonium tethered peptide ligand rapidly and selectively modifies protein cysteine in vicinity.

Chem Sci 2019 May 25;10(19):4966-4972. Epub 2019 Mar 25.

State Key Laboratory of Chemical Oncogenomics , School of Chemical Biology and Biotechnology , Peking University Shenzhen Graduate School , Shenzhen , 518055 , China . Email: ; Email:

Significant efforts have been invested to develop site-specific protein modification methodologies in the past two decades. In most cases, a reactive moiety was installed onto ligands with the sole purpose of reacting with specific residues in proteins. Herein, we report a unique peptide macrocyclization method the bis-alkylation between methionine and cysteine to generate cyclic peptides with significantly enhanced stability and cellular uptake. Notably, when the cyclized peptide ligand selectively recognizes its protein target with a proximate cysteine, a rapid nucleophilic substitution could occur between the protein Cys and the sulfonium center on the peptide to form a conjugate. The conjugation reaction is rapid, facile and selective, triggered solely by proximity. The high target specificity is further proved in cell lysate and hints at its further application in activity based protein profiling. This method enhances the peptide's biophysical properties and generates a selective ligand-directed reactive site for protein modification and fulfills multiple purposes by one modification. This proof-of-concept study reveals its potential for further broad biological applications.
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http://dx.doi.org/10.1039/c9sc00034hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530539PMC
May 2019

Characterization of a group D anti-lipopolysaccharide factor (ALF) involved in anti-Vibrio response in Penaeus monodon.

Fish Shellfish Immunol 2019 Jun 2;89:384-392. Epub 2019 Apr 2.

Shenzhen Key Laboratory of Marine Bioresource & Eco-environmental Science, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518060, PR China; Guangdong Technology Research Center for Marine Algal Bioengineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518060, PR China. Electronic address:

Antimicrobial peptides (AMPs) are an essential component of innate immunity of invertebrates. Anti-lipopolysaccharide factor (ALF), as a main type of AMPs in crustaceans, attends in the disease prevention in general. In this research, a novel Group D ALF was identified and characterized from Penaeus monodon, named PenmonALF8. It was an anionic peptide, with both the full-length peptide and lipopolysaccharide binding domain (LBD) a low isoelectric point. PenmonALF8, composed of a signal peptide of 26 amino acids and a mature peptide of 98 amino acids, probably contained three alpha helixes and four beta sheets. Moreover, PenmonALF8 was detected in all tested tissues of P. monodon, and the expression level in hemocyte and intestine was relatively high. When challenged by Vibrio parahaemolyticus, PenmonALF8 showed 30-100 times higher expression level in all the tissues except in hemocyte and intestine, indicating that PenmonALF8 played a very important role in the immune response of P. monodon. By fusing to a SUMO protein, PenmonALF8 was successfully over-expressed in E. coli and purified by affinity chromatography. Additionally, the reconstituted PenmonALF8 and its LBD region displayed modest antimicrobial activity. This is the first research about the Group D ALF in P. monodon, which provides more information for humoral immunity study of shrimps.
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http://dx.doi.org/10.1016/j.fsi.2019.03.049DOI Listing
June 2019

Effect of Covalent Interaction with Chlorogenic Acid on the Allergenic Capacity of Ovalbumin.

J Agric Food Chem 2018 Sep 7;66(37):9794-9800. Epub 2018 Sep 7.

Ovalbumin (OVA) is a major allergen in avian egg white. Here, we investigated the conjugation of OVA and chlorogenic acid (CHA) to reduce the allergenic capacity of OVA. OVA-CHA conjugate was characterized by SDS-PAGE, MALDI-TOF-MS, differential scanning calorimetry, and multispectroscopic methods. Sites of the OVA-CHA conjugate were identified by LC-MS/MS. CHA possibly conjugated with Lys20 and Lys17 in OVA, which resulted in the unfolding of OVA. ELISA and Western blot assay indicated that the OVA-CHA conjugate reduced the IgE binding capacity of OVA. The results also indicated that the ability of the OVA-CHA conjugate to activate histamine release was reduced. The decreased allergenic capacity of OVA was attributed to changes in the protein structure. Moreover, the CHA binding site in OVA might directly shield the linear IgE epitope, thereby reducing the IgE binding ability. Also, the OVA-CHA conjugate showed high antioxidant activity. OVA conjugated with CHA may be a promising method of OVA hyposensitization.
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http://dx.doi.org/10.1021/acs.jafc.8b03410DOI Listing
September 2018

PHF20L1 antagonizes SOX2 proteolysis triggered by the MLL1/WDR5 complexes.

Lab Invest 2018 12 8;98(12):1627-1641. Epub 2018 Aug 8.

State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology & Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.

Transcriptional factor SOX2 regulates stem cell pluripotency, cell differentiation and tumorigenesis. As a key factor, the expression of SOX2 is tightly regulated at transcriptional and post-translational levels. However, the underlying mechanism of SOX2 protein stability remains to be elucidated. Here we show that the histone-lysine N-methyltransferase MLL1/WDR5 complexes physically interact with SOX2 and evoke SOX2 proteolysis, possibly through methylation on a potential site lysine 42 (K42). Small interfering RNA (siRNA)-mediated gene silencing of the components of the MLL1/WDR5 complexes WDR5, MLL1, RBBP5, and ASH2L lead to the accumulation of SOX2, while forced expression of WDR5 promotes SOX2 ubiquitination and proteolysis. Conversely, PHD finger protein 20-like protein 1 (PHF20L1) associates with SOX2, antagonizes SOX2 ubiquitination and the sequential degradation induced by the MLL1/WDR5 complexes. RNA interferences of PHF20L1 promote the degradation of SOX2, while forced expression of PHF20L1 stabilizes SOX2. Co-silencing of MLL1/WDR5 components and PHF20L1 preclude degradation of SOX2 induced by knockdown of PHF20L1. Moreover, co-expression of PHF20L1 and WDR5 prevent ubiquitination of SOX2 triggered by WDR5 over-expression. However, SOX2 mutant K42R is non-sensitive to the MLL1/WDR5 complexes or PHF20L1. In addition, PHF20L1 may regulate the stability of SOX2 through its malignant brain tumor (MBT) domain, since the degradation of SOX2 is accelerated by UNC1215 and UNC669, inhibitors that bind to the MBT domain. Furthermore, abundant expression of SOX2 is highly correlated to immature ovarian teratoma. Loss of PHF20L1 weakened the tumor initiation ability of PA-1 cells while ablation of MLL1 promoted the growth of tumors. Thus, our studies reveal an antagonistic mechanism by which the protein stability of SOX2 is regulated by the MLL1/WDR5 complexes and PHF20L1, possibly through methylation of SOX2 protein, and provide a novel perspective on SOX2-positive cancer treatment.
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http://dx.doi.org/10.1038/s41374-018-0106-8DOI Listing
December 2018

Urine-Based Biomarkers for Alzheimer's Disease Identified Through Coupling Computational and Experimental Methods.

J Alzheimers Dis 2018 ;65(2):421-431

College of Life Science and Oceanography, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, China.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder contributing to nearly 70% of dementia cases. However, no diagnostic protein biomarkers are available in urine. In this study, we combined computational and experimental methods to identify urinary biomarkers for AD. First, by analyzing brain tissue-based gene expression data of AD, 2,754 differentially expressed genes were identified, 559 of which were predicted to encode urine-excretory proteins that might act as candidate protein biomarkers of AD. GO enrichment analyses implied that they were mainly involved in microtubule-based process, myelin sheath, and calcium ion binding, suggesting that they might be associated with AD pathogenesis. In order to verify these proteins in urine, an iTRAQ experiment was carried out to analyze urine samples from AD patients and healthy controls, and 15 proteins were detected. Based on the expression changes of these proteins, 4 proteins were chosen for further validation by ELISA experiment, and SPP1, GSN, and IGFBP7 were found to be differentially expressed in the urine of AD patients. After a literature survey, we found that they were involved in AD pathophysiology and might serve as new urine biomarkers for AD. To our knowledge, this is the first time that urine biomarkers for AD were identified by combining computational and experimental methods. Furthermore, this is the first time SPP1, GSN, and IGFBP7 have been reported as potential urine protein biomarkers for AD. Therefore, our findings might provide significant guidance for finding early biomarkers of AD in urine.
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http://dx.doi.org/10.3233/JAD-180261DOI Listing
August 2019

Effective lock-in strategy for proteomic analysis of corona complexes bound to amino-free ligands of gold nanoparticles.

Nanoscale 2018 Jul;10(26):12413-12423

Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.

For specific applications, gold nanoparticles (GNPs) are commonly functionalized with various biological ligands, including amino-free ligands such as amino acids, peptides, proteins, and nucleic acids. Upon entering a biological fluid, the protein corona that forms around GNPs can conceal the targeting ligands and sterically hinder the functional properties. The protein corona is routinely prepared by standard centrifugation or sucrose cushion centrifugation. However, such methodologies are not applicable to the exclusive analysis of a ligand-binding protein corona. In this study, we first proposed a lock-in strategy based on a combination of rapid crosslinking and stringent washing. Cysteine was used as a model of amino-free ligands and attached to GNPs. After corona formation in the human plasma, GNP cysteine and corona proteins were quickly fixed by 5 s of crosslinking with 7.5% formaldehyde. After stringent washing using SDS buffer with sonication, the cysteine-bound proteins were effectively separated from unbound proteins. Qualitative and quantitative analyses using a mass spectrometry-based proteomics approach indicated that the protein composition of the cysteine-binding corona from the new method was significantly different from the composition of the whole corona from the two conventional methods. Furthermore, network and formaldehyde-linked site analyses of cysteine-binding proteins provided useful information toward a better knowledge of the behavior of protein-ligand and protein-protein interactions. Collectively, our new strategy has the capability to particularly characterize the protein composition of a cysteine-binding corona. The presented methodology in principal provides a generic way to analyze a nanoparticle corona bound to amino-free ligands and has the potential to decipher corona-masked ligand functions.
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http://dx.doi.org/10.1039/c8nr01077cDOI Listing
July 2018

Autophosphorylation Mechanism of the Ser/Thr Kinase Stk1 From .

Front Microbiol 2018 20;9:758. Epub 2018 Apr 20.

School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.

The eukaryotic-like Ser/Thr kinase Stk1 is crucial for virulence, cell wall biosynthesis, and drug susceptibility in methicillin-resistant () (MRSA). Importantly, MRSA lacking Stk1 become sensitive to β-lactam antibiotics, implying that Stk1 could be an alternative target for combination therapy. However, the autophosphorylation mechanism of Stk1 remains elusive. Using a phosphoproteomic study, we identified six phosphorylated activation loop residues (Ser159, Thr161, Ser162, Thr164, Thr166, and Thr172) of Stk1, which are also phosphorylated . We further showed that autophosphorylation of Thr172 in the GT/S motif is essential for self-activation and kinase activity of Stk1 kinase domain (Stk1-KD), whereas the autophosphorylation of other activation loop serines/threonines are required for the optimal kinase activity of Stk1-KD. Moreover, substitution of the activation loop serines/threonines impaired autophosphorylation activity of kinase variants, while T172A and T172D variants were unable to autophosphorylate in the cellular content, underlining the essential role of Thr172 for Stk1 activity . This study provides insights into molecular basis for regulation of Stk1 activity from .
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http://dx.doi.org/10.3389/fmicb.2018.00758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920020PMC
April 2018

Blocking the Thiol at Cysteine-322 Destabilizes Tau Protein and Prevents Its Oligomer Formation.

ACS Chem Neurosci 2018 07 3;9(7):1560-1565. Epub 2018 May 3.

Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Sciences, College of Life Sciences and Oceanography , Shenzhen University , Shenzhen 518060 , China.

Abnormal accumulation of tau protein into oligomers contributes to neuronal dysfunction. Reduction of tau level is potentially able to prevent its accumulation. Here we uncover a critical role of the free thiol at Cys-322 in determining tau stability. We found that the application of thiol-blocking agents like NEM or MMTS blocks this thiol, by which it destabilizes tau protein and prevents its oligomer formation. Furthermore, we identified a tau-interacting protein, selenoprotein W, which attenuates tau accumulation by forming disulfide linkage between SelW Cys-37 and tau Cys-322. These findings provide a promising strategy to prevent tau accumulation and oligomer formation.
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http://dx.doi.org/10.1021/acschemneuro.8b00003DOI Listing
July 2018

Quantitative Proteomic Analysis Reveals Synaptic Dysfunction in the Amygdala of Rats Susceptible to Chronic Mild Stress.

Neuroscience 2018 04 13;376:24-39. Epub 2018 Feb 13.

Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. Electronic address:

The amygdala plays a key role in the pathophysiology of depression, but the molecular mechanisms underlying amygdalar hyperactivity in depression remain unclear. In this study, we used a chronic mild stress (CMS) protocol to separate susceptible and insusceptible rat subgroups. Proteomes in the amygdalae were analyzed differentially across subgroups based on labeling with isobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry. Of 2562 quantified proteins, 102 were differentially expressed. Several proteins that might be associated with the stress insusceptibility/susceptibility difference, including synapse-related proteins, were identified in the amygdala. Immunoblot analysis identified changes in VGluT1, NMDA GluN2A and GluN2B and AMPA GluA1 receptors, and PSD-95, suggesting that CMS perturbs glutamatergic transmission in the amygdala. Changes in these regulatory and structural proteins provide insight into the molecular mechanisms underlying the abnormal synaptic morphological and functional plasticity in the amygdalae of stress-susceptible rats. Interestingly, the expression level of CaMKIIβ, potentially involved in regulation of glutamatergic transmission, was significantly increased in the susceptible group. Subsequent in vitro experimentation showed that overexpression of CaMKIIβ increased the expression of PSD-95 and GluA1 in cultured hippocampal neurons. This result suggested that CaMKIIβ functions upstream from PSD-95 and GluA1 to affect LTP-based postsynaptic functional plasticity in the amygdalae of susceptible rats. Therefore, amygdalar CaMKIIβ is a potential antidepressant target. Collectively, our findings contribute to a better understanding of amygdalar synaptic plasticity in depression.
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http://dx.doi.org/10.1016/j.neuroscience.2018.02.010DOI Listing
April 2018

iTRAQ-Based Proteomic Analysis Reveals Protein Profile in Plasma from Children with Autism.

Proteomics Clin Appl 2018 05 18;12(3):e1700085. Epub 2018 Jan 18.

Maternal and Child Health Hospital of Baoan, Shenzhen, P. R. China.

Purpose: Autism is a childhood neurological disorder with poorly understood etiology and pathology. This study is designed to identify differentially expressed proteins that might serve as potential biomarkers for autism.

Experimental Design: We perform iTRAQ (isobaric tags for relative and absolute quantitation) analysis for normal and autistic children's plasma of the same age group.

Results: The results show that 24 differentially expressed proteins were identified between autistic subjects and controls. For the first time, differential expression of complement C5 (C5) and fermitin family homolog 3 (FERMT3) are related to autism. Five proteins, that is, complement C3 (C3), C5, integrin alpha-IIb (ITGA2B), talin-1 (TLN1), and vitamin D-binding protein (GC) were validated via enzyme-linked immunosorbent assay (ELISA). By ROC (receiver operating characteristic) analysis, combinations of these five proteins C3, C5, GC, ITGA2B, and TLN1 distinguished autistic children from healthy controls with a high AUC (area under the ROC curve) value (0.982, 95% CI, 0.957-1.000, p < 0.000).

Conclusion: These above described proteins are found involved in different pathways that have previously been linked to the pathophysiology of autism spectrum disorders (ASDs). The results strongly support that focal adhesions, acting cytoskeleton, cell adhesion, motility and migration, synaptogenesis, and complement system are involved in the pathogenesis of autism, and highlight the important role of platelet function in the pathophysiology of autism.
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http://dx.doi.org/10.1002/prca.201700085DOI Listing
May 2018

Oxygen Supplementation Improves Protein Milieu Supportive of Protein Synthesis and Antioxidant Function in the Cortex of Alzheimer's Disease Model Mice-a Quantitative Proteomic Study.

J Mol Neurosci 2017 Oct 21;63(2):243-253. Epub 2017 Sep 21.

College of Life Sciences and Oceanography, Shenzhen Key Laboratory of Marine Bioresources and Ecology, Shenzhen University, Shenzhen, China.

Protein synthesis has been reported to be impaired in early-stage Alzheimer's disease (AD). Previously, we found that oxygen supplementation improved cognitive function and reduced mitochondrial damage in AD model mice. In the present study, we examined the effects of supplemental oxygen treatment on protein synthesis and oxidative damage. The synthesis of numerous proteins involved in mRNA splicing, transcription regulation, and translation was found to be significantly upregulated in cortex tissues of AD model mice given a supplemental oxygen treatment (OT group), relative to those of non-treated control AD model mice (Ctrl group), suggesting that impairment in protein synthesis may be alleviated by increased oxygen inhalation. Methionine oxidation and oxidation levels in general were similar between the OT and Ctrl groups, indicating that the oxygen supplementation treatment did not cause increases in peptide oxidation levels. On the contrary, the OT group exhibited upregulation of several proteins associated with antioxidant defense. These results support further exploration into the development of supplementary oxygen treatment as a potential therapy for AD.
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http://dx.doi.org/10.1007/s12031-017-0975-0DOI Listing
October 2017

The effect of phosphorylation on the salt-tolerance-related functions of the soybean protein PM18, a member of the group-3 LEA protein family.

Biochim Biophys Acta Proteins Proteom 2017 Nov 1;1865(11 Pt A):1291-1303. Epub 2017 Sep 1.

Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd. MDC07, Tampa, FL, USA; Laboratory of New Methods in Biology, Institute for Biological Instrumentation, Russian Academy of Sciences, Institutskaya str., 7, Pushchino, Moscow region 142290, Russia; Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., St. Petersburg 194064, Russia. Electronic address:

Enzymatically driven post-translated modifications (PTMs) usually happen within the intrinsically disordered regions of a target protein and can modulate variety of protein functions. Late embryogenesis abundant (LEA) proteins are a family of the plant intrinsically disordered proteins (IDPs). Despite their important roles in plant stress response, there is currently limited knowledge on the presence and functional and structural effects of phosphorylation on LEA proteins. In this study, we identified three phosphorylation sites (Ser, Tyr, and Thr) in the soybean PM18 protein that belongs to the group-3 LEA proteins. In yeast expression system, PM18 protein increased the salt tolerance of yeast, and the phosphorylation of this protein further enhanced its protective function. Further analysis revealed that Ser and Tyr are more important than Thr, and these two sites might work cooperatively in regulating the salt resistance function of PM18. The circular dichroism analysis showed that PM18 protein was disordered in aqueous media, and phosphorylation did not affect the disordered status of this protein. However, phosphorylation promoted formation of more helical structure in the presence of sodium dodecyl sulfate (SDS) or trifluoroethanol (TFE). Furthermore, in dedicated in vitro experiments, phosphorylated PM18 protein was able to better protect lactate dehydrogenase (LDH) from the inactivation induced by the freeze-thaw cycles than its un- or dephosphorylated forms. All these data indicate that phosphorylation may have regulatory effects on the stress-tolerance-related function of LEA proteins. Therefore, further studies are needed to shed more light on functional and structural roles of phosphorylation in LEA proteins.
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http://dx.doi.org/10.1016/j.bbapap.2017.08.020DOI Listing
November 2017

Proteomic and network analysis of human serum albuminome by integrated use of quick crosslinking and two-step precipitation.

Sci Rep 2017 08 29;7(1):9856. Epub 2017 Aug 29.

Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Affinity- and chemical-based methods are usually employed to prepare human serum albuminome; however, these methods remain technically challenging. Herein, we report the development of a two-step precipitation (TSP) method by combined use of polyethylene glycol (PEG) and ethanol. PEG precipitation was newly applied to remove immunoglobulin G for albuminome preparation, which is simple, cost effective, efficient and compatible with downstream ethanol precipitation. Nonetheless, chemical extraction using TSP may disrupt weak and transient protein interactions with human serum albumin (HSA) leading to an incomplete albuminome. Accordingly, rapid fixation based on formaldehyde crosslinking (FC) was introduced into the TSP procedure. The developed FC-TSP method increased the number of identified proteins, probably by favouring real-time capture of weakly bound proteins in the albuminome. A total of 171 proteins excluding HSA were identified from the fraction obtained with FC-TSP. Further interaction network and cluster analyses revealed 125 HSA-interacting proteins and 14 highly-connected clusters. Compared with five previous studies, 55 new potential albuminome proteins including five direct and 50 indirect binders were only identified by our strategy and 12 were detected as common low-abundance proteins. Thus, this new strategy has the potential to effectively survey the human albuminome, especially low-abundance proteins of clinical interest.
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http://dx.doi.org/10.1038/s41598-017-09563-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575314PMC
August 2017

Mosapride Stabilizes Intestinal Microbiota to Reduce Bacterial Translocation and Endotoxemia in CCl-Induced Cirrhotic Rats.

Dig Dis Sci 2017 10 16;62(10):2801-2811. Epub 2017 Aug 16.

Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, 208 Huancheng Dong Road, Hangzhou, 310003, China.

Background: Impaired intestinal motility may lead to the disruption of gut microbiota equilibrium, which in turn facilitates bacterial translocation (BT) and endotoxemia in cirrhosis. We evaluated the influence of mosapride, a prokinetic agent, on BT and DNA fingerprints of gut microbiota in cirrhotic rats.

Methods: A rat model of cirrhosis was set up via subcutaneous injection of carbon tetrachloride (CCl). The portal pressure, liver and intestinal damage, plasma endotoxin, BT, and intestinal transit rate (ITR) of cirrhotic rats were determined. Fecal DNA fingerprints were obtained by ERIC-PCR. The expressions of tight junction proteins were evaluated by western blotting.

Results: Mosapride treatment to cirrhotic rats significantly reduced the plasma endotoxin level and incidence of BT, accompanied by increased ITR. Cirrhotic rats (including those treated with mosapride) suffered from BT exhibited significantly lower ITR than those who are free of BT. Pearson coefficient indicated a significant and negative correlation between the plasma endotoxin level and ITR. The genomic fingerprints of intestinal microbiota from the three groups fell into three distinctive clusters. In the mosapride-treated group, Shannon's index was remarkably increased compared to the model group. Significantly positive correlation was detected between Shannon's index and ITR. Mosapride did not improve hepatic and intestinal damages and ileal expressions of occludin and ZO-1.

Conclusions: Mosapride significantly increases intestinal motility in cirrhotic rats, thus to recover the disordered intestinal microbiota, finally resulting in decreased plasma endotoxin and BT.
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http://dx.doi.org/10.1007/s10620-017-4704-xDOI Listing
October 2017

High Rab25 expression associates with Ki67/TP53/CD133/VEGFR expression predicts poor prognosis in gastric cancer.

Int J Clin Exp Pathol 2017 1;10(7):7792-7800. Epub 2017 Jul 1.

Department of Physical and Chemical Analysis, Shenzhen Nanshan Center for Disease Control and Prevention Shenzhen, Guangdong, China.

Rab25 belongs to Rab GTPases which regulating vesicle trafficking of various extracellular and intracellular resources. Aberrant high Rab25 expression is closely linked to cancer development including gastric cancer. However, the underlying mechanism of Ras25 in gastric cancer is still unclear. In this study, we determined to investigate the potential association between Rab25 and four tumor markers, including Ki67 (a well-known hallmarker of tumor proliferation), TP53 (tumor p53, a master tumor regulator associated with cell apoptosis), CD133 (a common cancer stem cell marker) and VEGFR (Vascular endothelial growth factor receptor, an efficient therapy target for gastric cancer). The results indicated that Rab25 expression in both cytoplasm and nucleus was significantly higher in gastric cancer tissues than para-carcinoma tissues. High Rab25 nucleus expression was positively associated with distant metastasis (M stage) and clinical (cTNM) stage, while Rab25 nucleus expression correlated with M stage, cTNM stage and regional lymph metastasis stage (N stage). Survival analysis revealed that high Rab25 cytoplasm/nucleus expression predicted shorter overall survival time of patients with gastric cancer. Rab25 expression was significantly associated with Ki67 expression, TP53 expression, CD133 expressionand VEGFR expression in gastric cancer. In conclusion, our results indicated that Rab25 behaved as an oncogene in gastric cancer related to Ki67/TP53/CD133/VEGFR expression and suggested Rab25 to be a prognostic marker.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965299PMC
July 2017

Intrinsically Disordered Proteins as Important Players during Desiccation Stress of Soybean Radicles.

J Proteome Res 2017 07 30;16(7):2393-2409. Epub 2017 May 30.

Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida , 12901 Bruce B. Downs Boulevard MDC07, Tampa, Florida 33612, United States.

Intrinsically disordered proteins (IDPs) play a variety of important physiological roles in all living organisms. However, there is no comprehensive analysis of the abundance of IDPs associated with environmental stress in plants. Here, we show that a set of heat-stable proteins (i.e., proteins that do not denature after boiling at 100 °C for 10 min) was present in R and R radicles (i.e., before radicle emergence and 15 mm long radicles) of soybean (Glycine max) seeds. This set of 795 iTRAQ-quantified heat-stable proteins contained a high proportion of wholly or highly disordered proteins (15%), which was significantly higher than that estimated for the whole soybean proteome containing 55,787 proteins (9%). The heat-stable proteome of soybean radicles that contain many IDPs could protect lactate dehydrogenase (LDH) during freeze-thaw cycles. Comparison of the 795 heat-stable proteins in the R and R soybean radicles revealed that many of these proteins changed abundance during seedling growth with 170 and 89 proteins being more abundant in R and R, respectively. KEGG analysis identified 18 proteins from the cysteine and methionine metabolism pathways and nine proteins from the phenylpropanoid biosynthesis pathway. As an important type of IDP related to stress, 30 late embryogenesis abundant proteins were also found. Ten selected proteins with high levels of predicted intrinsic disorder were able to efficiently protect LDH from the freeze-thaw-induced inactivation, but the protective ability was not correlated with the disorder content of these proteins. These observations suggest that protection of the enzymes and other proteins in a stressed cell can be one of the biological functions of plant IDPs.
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http://dx.doi.org/10.1021/acs.jproteome.6b01045DOI Listing
July 2017

In-depth analysis of the synaptic plasma membrane proteome of small hippocampal slices using an integrated approach.

Neuroscience 2017 06 21;353:119-132. Epub 2017 Apr 21.

Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. Electronic address:

Comprehensive knowledge of the synaptic plasma membrane (SPM) proteome of a distinct brain region in a defined pathological state would greatly advance the understanding of the underlying biology of synaptic plasticity. The development of innovative approaches for studying the SPM proteome of small brain tissues is highly desired. This study presents a suitable protocol that integrates biotinylation-based affinity capture of cell surface-exposed proteins, isolation of synaptosomes, and biochemical extraction of SPM proteins from biotinylated hippocampal slices. The effectiveness of this integrated method was initially confirmed using immunoblot analysis of synaptic markers. Subsequently, we used highly sensitive mass spectrometry and streamlined bioinformatics to analyze the obtained SPM protein-enriched fraction. Our workflow positively identified 241 SPM proteins comprising 85 previously reported classical proteins from the pre- and/or post-synaptic membrane and 156 nonclassical proteins that localized to both the plasma membrane and synapse, and have not been previously reported as SPM proteins. Further analyses revealed considerable similarities in the physicochemical and functional properties of these proteins. Analysis of the interaction network using STRING indicated that the two groups showed a relatively strong functional correlation. Using MCODE analysis, we observed that 65 nonclassical SPM proteins formed 12 highly interconnected clusters with 47 classical SPM proteins, suggesting that they were the more likely SPM candidates. Taken together, the results of this study provide an integrated tool for analyzing the SPM proteome of small brain tissues, as well as a dataset of putative novel SPM proteins to improve the understanding of hippocampal synaptic plasticity.
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http://dx.doi.org/10.1016/j.neuroscience.2017.04.015DOI Listing
June 2017

EGFR induces DNA decomposition via phosphodiester bond cleavage.

Sci Rep 2017 03 8;7:43698. Epub 2017 Mar 8.

Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.

EGFR may induce DNA degradation. This activity had not been previously described as an EGRF function. To confirm this unexpected activity, testing of EGFR in the presence of ATP and either 5A, 5C, 5G, 5T, or 5U oligonucleotides was performed. HPLC-MS analysis demonstrated that 5A and 5U levels significantly decreased in the presence of EGFR. Furthermore, fragments 4A and 4U were produced in 5A+EGFR+ATP and in 5U+EGFR+ATP reaction mixtures, respectively, but not in EGFR-negative controls. Degradation of Poly(A), Poly(C), Poly(G), Poly(I), Poly(T), and Poly(U) oligomers in the presence of EGFR and ATP correlated with the lower ability of reaction products to pair with complementary oligonucleotides. Gel electrophoresis showed that breakdown products migrated more quickly than controls, especially after addition of paired (complementary) oligomers, Poly(A) and Poly(U). Furthermore, λ DNA reaction products also migrated more quickly after incubation with EGFR. The results suggest that EGFR can induce breakage of certain types of nucleotide phosphodiester bonds, especially within the A residues of DNA or U residues of RNA, to induce DNA or RNA decomposition, respectively. This activity may be important in EGRF signaling, DNA degradation, or repair in normal or cancer cell activities.
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http://dx.doi.org/10.1038/srep43698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341565PMC
March 2017

Proteomics Analysis of Blood Serums from Alzheimer's Disease Patients Using iTRAQ Labeling Technology.

J Alzheimers Dis 2017 ;56(1):361-378

College of Life Science and Oceanography, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, P.R. China.

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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http://dx.doi.org/10.3233/JAD-160913DOI Listing
February 2018

Quantitative Proteomics Reveals the Mechanism of Oxygen Treatment on Lenses of Alzheimer's Disease Model Mice.

J Alzheimers Dis 2016 08;54(1):275-86

College of Life Sciences and Oceanography, Shenzhen Key Laboratory of Marine Bioresources and Ecology, Shenzhen University, Shenzhen, China.

Background: Alzheimer's disease (AD) is a neurodegenerative disease with well-characterized pathological features. Yet the underlying mechanisms have not been resolved and an effective therapeutic approach is lacking. Cerebral hypoxia is considered a risk factor of AD.

Objective: We tested whether oxygen supplementation can relieve AD symptoms and how it affects the expression levels of proteins in the lens.

Methods: Triple transgenic AD model (3xTg-AD) mice were divided into oxygen treated (OT) and control (Ctrl) groups. Their cognitive performances were tested in a Morris water maze (MWM) paradigm. Then, their eye lens tissues were subjected to quantitative proteomics analysis by the iTRAQ (isobaric tags for relative and absolute quantification) method. The up- and downregulated proteins were classified according to a Gene Ontology (GO) database in PANTHER. Behavioral and proteomic data were compared between the groups.

Results: Mice in the OT group had better learning and memorizing performance compared with the Ctrl group in MWM test. Lenses from the OT group had 205 differentially regulated proteins, relative to lenses from the Ctrl group, including proteins that are involved in the clearance of amyloid β-protein.

Conclusion: The results of this study indicate that oxygen treatment can improve cognitive function in AD model mice and alters protein expression in a manner consistent with improved redox regulation.
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http://dx.doi.org/10.3233/JAD-160263DOI Listing
August 2016
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