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Pancreatic cancer cells treated with anlotinib

ABSTRACT: Aberrant regulation of angiogenesis involves in the growth and metastasis of tumors, but angiogenesis inhibitors fail to improve overall survival of pancreatic cancer patients in previous phase III clinical trials. A comprehensive knowledge of the mechanism of angiogenesis inhibitors against pancreatic cancer is helpful for clinical purpose and for the selection of patients who might benefit from the inhibitors. In this work, multi-omics analyses (transcriptomics, proteomics and phosphoproteomics profiling) were carried to delineate the mechanism of anlotinib, a novel angiogenesis inhibitor, against pancreatic cancer cells.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Zewen Song

LAB HEAD: Zewen Song

PROVIDER: PXD023344 | Pride | 2021-09-09

REPOSITORIES: Pride

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Multi-Omics Analysis of Anlotinib in Pancreatic Cancer and Development of an Anlotinib-Related Prognostic Signature.

Zhang Xi X Liu Yang Y Zhang Zhen Z Tan Juan J Zhang Junjun J Ou Hao H Li Jie J Song Zewen Z

Frontiers in cell and developmental biology 20210304

Aberrant regulation of angiogenesis involves in the growth and metastasis of tumors, but angiogenesis inhibitors fail to improve overall survival of pancreatic cancer patients in previous phase III clinical trials. A comprehensive knowledge of the mechanism of angiogenesis inhibitors against pancreatic cancer is helpful for clinical purpose and for the selection of patients who might benefit from the inhibitors. In this work, multi-omics analyses (transcriptomics, proteomics, and phosphoproteomi ...[more]

PMID: 33748143

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Phosphoproteomics Data of pancreatic cancers cells treated with anlotinib

Project description:Aberrant regulation of angiogenesis involves in the growth and metastasis of tumors, but angiogenesis inhibitors fail to improve overall survival of pancreatic cancer patients in previous phase III clinical trials. A comprehensive knowledge of the mechanism of angiogenesis inhibitors against pancreatic cancer is helpful for clinical purpose and for the selection of patients who might benefit from the inhibitors. In this work, multi-omics analyses (transcriptomics, proteomics and phosphoproteomics profiling) were carried to delineate the mechanism of anlotinib, a novel angiogenesis inhibitor, against pancreatic cancer cells.

2021-09-09 | PXD023345 | Pride

Comparative analysis of serum proteins between hepatitis B virus genotype B and C infection DIA-based quantitative proteomics

Project description:Hepatitis B virus (HBV) is an enveloped, coated, non-cytopathic and hepatotropic partially double-stranded DNA virus in the family Hepadnaviridae genus Orthohepadnavirus. Despite significant progress in the availability of safe vaccines and antiviral therapies against HBV, it still affects approximately 257 million people worldwide and is responsible for about 887,000 deaths per year around the world [4]. HBV infection, which are associated with acute and chronic liver failure responses to viruses attacked the liver, can result in inactive carrier state, chronic hepatitis, or fulminant hepatitis and put them at high risk to develop advanced liver fibrosis and cirrhosis, and even hepatocellular cancer. Many viral factors, which could affect the disparity of clinical outcomes or disease prognosis during chronic HBV infection, have been reported in previous studies; among them, the viral genotype, as well as HBV mutations ascribing the virus to a certain phenotype, was reported to be the most important factor influencing viral pathogenesis, including the change of host immune recognition, the enhanced virulence with increased HBV replication and the facilitation of cell attachment or penetration.

2022-02-17 | PXD025968 | Pride

Serum proteomic profiling in patients with advanced Schistosoma japonicum-induced hepatic fibrosis

Project description:Background: Schistosoma japonicum (S. japonicum) is a parasitic flatworm that is the aetiological agent of human schistosomiasis, an important cause of hepatic fibrosis. Schistosomiasis-induced hepatic fibrosis is a consequence of the highly fibrogenic nature of egg-induced granulomatuous lesions, the main pathogenic factor of schistosomiasis. Although global awareness of the association between schistosomiasis-indued hepatic fibrosis and s. japonicum infection is increasing, little is known about the molecular differences associated with rapid progression to schistosomiasis in cirrhotic patients. Methods: We systematically used data-independent acquisition (DIA)-based liquid chromatography-mass spectrometry to identify differentially expressed proteins in serum samples from patients with advanced S. japonicum-induced hepatic fibrosis. Results: On the basis of our analysis, we identified 1,144 proteins, among which 66 were differentially expressed between the healthy control and SHF-F2 groups and 214 were differentially expressed between the SHF-F2 and SHF-F4 groups (up- or downregulation of at least 1.5-fold in serum samples). Furthermore, our results indicated that two selected proteins (C1QA and CFD) are potential biomarkers for distinguishing patients with SHF-F2 and SHF-F4 resulting from S. japonicum infection. Conclusions: This report is the first to provide a global proteomic profile of serum samples from patients with advanced S. japonicum-induced hepatic fibrosis. C1QA and CFD are potentially diagnostic markers for patients with SHF-F2 and SHF-F4 resulting from S. japonicum infection, although further large-scale studies are needed. Our DIA-based quantitative proteomic analysis revealed molecular differences among individuals with different stages of advanced S. japonicum-induced hepatic fibrosis and might provide fundamental information for further detailed investigations.

2022-09-06 | PXD025224 | Pride

Pathogenic Bacteria Exploit Transferrin Receptor Transcytosis to Penetrate the Blood‒Brain Barrier

Project description:In this study, we present evidence showing that the infection with the major meningitis-causing bacteria, NMEC, GBS and SPN, activates the same fusion process of bacteria-containing vesicles (BCVs) with TfR vesicles, which enables those bacteria to exploit TfR transcytosis to penetrate the BBB, and illustrate the details of this process in HBMECs and mouse models.

2023-10-24 | PXD039060 | Pride

Two novel zinc and cobalt-responsive proteins in marine eukaryotic phytoplankton and implications for Zn scarcity in the surface oceans

Project description:Observations of scarce surface ocean concentrations of dissolved zinc (Zn) have raised the possibility that Zn may co-limit the growth of oceanic phytoplankton, yet testing this hypothesis has been difficult because Zn is highly prone to contamination. Biomarkers of micro-nutrient stress can serve as an alternate means to assay, though biomarker proteins for Zn stress in marine algae are currently uncharacterized. In this study we identified two Zn-responsive proteins in four marine diatom species that became abundant under Zn and Co limitation, but were scarce or undetectable in replete conditions. We refer to these proteins as ZCRP-A and ZCRP-B (Zn/Co Responsive Protein A and B). Sequence similarity of ZCRP-A to the Escherichia coli model COG0523 protein YjiA suggests a Zn2+ binding capability using conserved metal binding sites. Cellular localization by fluorescent tagging and overexpression of these proteins showed that ZCRP-B is part of a membrane-bound transport complex and that ZCRP-A serves as a Zn/Co chaperone with a chloroplastic target. These results imply that ZCRP-A and ZCRP-B are important in intracellular Zn trafficking and high-affinity transport, respectively. Metaproteomic detection of ZCRP-A and ZCRP-B homologs in a variety of eukaryotic protists along a South Pacific Ocean transect demonstrated that both proteins were more abundant in the euphotic zone (0-200m) where dZn and dCo were scarce. These findings describe widely distributed marine algal proteins linked to Zn and Co metabolism that together contribute to our understanding of Zn homeostasis in important marine phytoplankton.

2022-03-02 | PXD026953 | Pride

Comparative TMT-based quantitative proteomic analysis of the Tachaea chinensis isopod during parasitism

Project description:Parasitic isopods perforate and attach to the host integument via the mandibles, then feed on hemolymph and exudate from the wounds. Such isopods attack a variety of commercially important fish and crustacean hosts. Like other hematophagous parasites, isopods employ biomolecules that inhibit host blood conglutination and defense. In the present study, a tandem mass tag-based quantitative proteomic approach was used to identify differentially expressed proteins in Tachaea chinensis parasites of shrimp, by comparing parasitic (fed) and pre-parasitic (unfed) individuals. We identified 888 proteins from 1510 total peptides, with a significant difference in 129 between the fed and unfed groups. Among these, 37 were upregulated and 92 were downregulated in unfed T. chinensis. This indicates that T. chinensis may require more energy before parasitism during its search for a host. In addition, as is the case for other blood-sucking parasites, it might secrete antihemostatic, anti-inflammatory and immunomodulatory molecules to facilitate blood meal acquisition. Our study is the first to use a TMT-based proteomic approach to analyze the proteome of isopod parasites, and our results will facilitate our understanding of the molecular mechanisms of isopod parasitism on crustaceans.

2020-05-26 | PXD015247 | Pride

Nitric Oxide Enhances Resistance to PEG-induced Water Deficiency is Associated with the Primary Photosynthesis Reaction in Triticum aestivum L.

Project description:Photosynthesis is affected by water deficiency (WD) stress, and nitric oxide (NO) is a free radical that participates in the photosynthesis process. Previous studies have suggested that NO regulates the excitation energy distribution of photosynthesis under WD stress. Here, quantitative phosphoproteomic profiling was conducted using isobaric tags for relative and absolute quantitation. Differentially phosphorylated protein species (DEPs) were identified in leaves of NO or polyethylene glycol (PEG)-treated wheat seedlings (D) and in control seedlings, 2,257 unique phosphorylated peptides and 2,416 phosphorylation sites were identified from 1,396 unique phosphoproteins. Of these, 96 DEPs displayed significant changes (≥ 1.50-fold, p < 0.01). These DEPs are involved in photosynthesis and signal transduction, etc. Furthermore, phosphorylation of several DEPs were up-regulated by both D and NO treatments, but down-regulated only in NO treatment. These differences affected the chlorophyll A-B binding protein, chloroplast post-illumination chlorophyll fluorescence increase protein, and SNT7, implying that NO indirectly regulated the absorption and transport of light energy in photosynthesis in response to WD stress. The significant difference of chlorophyll (Chl) content, Chl a fluorescence transient, photosynthesis index, and trapping and transport of light energy further indicated that exogenous NO under D stress enhanced the primary reaction of photosynthesis compared to D treatment. A putative pathway is proposed to elucidate NO regulation of the primary reaction of photosynthesis under WD.

2019-11-14 | PXD010724 | Pride

Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction

Project description:Metabolic reprogramming is a hallmark of the immune cells in response to inflammatory stimuli. This metabolic process involves a switch from oxidative phosphorylation (OXPHOS)to glycolysis, or alterations in other metabolic pathways. However, most of the experimental findings have been acquired in murine immune cells and little is known about the metabolic reprogramming of human microglia. In this study, we investigated the transcriptomic and metabolic profiles of mouse and iPSC-derived human microglia challenged with the TLR4 agonist LPS. We found that both species displayed a metabolic shift and an overall increased glycolytic gene signature in response to LPS treatment. The metabolic reprogramming was characterized by the upregulation of hexokinases in mouse microglia and phosphofructokinases in human microglia. This study provides the first direct comparison of energy metabolism between mouse and human microglia, highlighting the species-specific pathways involved in immunometabolism and the importance of considering these differences in translational research.

2023-09-02 | PXD043836 | Pride

A proteomics of gills approach to understanding salinity adaptation of Scylla paramamosain

Project description:Scylla paramamosain (Crustacea) is a commercially important euryhaline species distributed along the coast of southern China and other Indo-Pacific countries. However, a sudden variation in salinity will cause injury or even death of S. paramamosain. In this paper, we simulated a sudden decrease in salinity due to heavy precipitation in crab ponds. Comparison of gill microstructures of individuals in the control group and decreased salinity group showed gills became shorter and thicker, while the top of the filaments became swollen and then returned to normal after 120 h. A total of 3962 proteins were identified by proteomic sequencing of gills after 120 h under conditions of decreased salinity. 845 proteins were differentially expressed proteins: 371 up-regulated and 474 down-regulated. Of the enriched KEGG pathways, 20 were up-regulated and 14 were down-regulation (p<0.05). Among the significantly enriched up-regulated pathways, six were associated with amino acid metabolism and three were associated with Na+-K+-ATPase enzymatic activities. Pathways associated with redox metabolism and energy metabolism were identified. These results showed that in response to a decrease in salinity, S. paramamosain could adapt to the environment after 120 h. Molecular mechanism of this adaptation involved amino acid metabolism and Na+-K+-ATPase ion transport. Meanwhile, energy metabolism and redox metabolism were critical to the adaptation to a sudden decrease in salinity. This study, for the first time at the protein level, revealed the molecular mechanisms underlying salinity adaption of S. paramamosain and provides theoretical guidelines for the cultivation of S. paramamosain and other marine crustaceans.

2018-07-31 | PXD009179 | Pride

Chemoproteomics Reveals Chemical Diversity and Dynamics of 4-Oxo-2-nonenal Modifications in Cells

Project description:4-Oxo-2-nonenal (ONE) derived from lipid peroxidation modifies nucleophiles and transduces redox signaling by its reactions with proteins. However, the molecular interactions between ONE and complex proteomes and their dynamics in situ remain largely unknown. Here we de-scribe a quantitative chemoproteomic analysis of protein adduction by ONE in cells, in which the cellular target profile of ONE is mimicked by its alkynyl surrogate. The analysis reveals four types of ONE-derived modifications in cells, including ketoamide and Schiff-base adducts to lysine, Michael adducts to cysteine, and a novel pyrrole adducts to cysteine. ONE-derived adducts co-localize and crosstalk with many histone marks and redox sensitive sites. All four types of modifications derived from ONE can be reversed site-specifically in cells. In summary, our study provides much-needed mechanistic insights into the cellular signaling and potential toxicities associated with this important lipid derived electrophile.

2022-02-24 | PXD006680 | Pride

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