Dataset Information

Serum protein profile in LPS-induced mice model by two-dimensional LC-MS/MS

ABSTRACT: Serum is an ideal source of biomarkers because of easy accessibility, noninvasiveness, and rapid response to disease. Given that the different clinical manifestation between early phase and late phase of sepsis, the change of serum proteins profile during different phase of sepsis can give insight into predictor for early diagnosis of sepsis. In this study, differential serum proteins were screened in mice treated with lipopolysaccharide (LPS) for 2 h, 24 h and controls using free-labeling coupled with two-dimensional liquid chromatography and tandem mass spectrometry (2D LC-MS/MS) technique.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Serum

SUBMITTER: Chunxia Wang

LAB HEAD: Chunxia Wang

PROVIDER: PXD014259 | Pride | 2020-05-26

REPOSITORIES: Pride

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Publications

Apolipoprotein A-V Is a Novel Diagnostic and Prognostic Predictor in Pediatric Patients with Sepsis: A Prospective Pilot Study in PICU.

Wang Chunxia C Cui Yun Y Miao Huijie H Xiong Xi X Dou Jiaying J Shao Lujing L Tang Xiaomeng X Zhang Yucai Y

Mediators of inflammation 20200113

<h4>Background</h4>Sepsis induces the release of lipid mediators, which control both lipid metabolism and inflammation. However, the role of serum apolipoprotein A-V (ApoA5) in sepsis is poorly understood in pediatric patients.<h4>Methods</h4>ApoA5 was screened from serum proteomics profile in lipopolysaccharide- (LPS-) treated mice for 2 h, 24 h, and controls. Then, we conducted a prospective pilot study, and patients with sepsis admitted to a pediatric intensive care unit (PICU) were enrolled ...[more]

PMID: 32322166

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Project description:Background: Sepsis-associated encephalopathy (SAE) is a common and severe complication of sepsis. While several studies have reported the proteomic alteration in plasma, urine, heart, etc. of sepsis, few research focused on the brain tissue. This study aims at discovering the differentially abundant proteins in the brains of septic rats to identify biomarkers of SAE. Methods: The Prague-Dawley rats were randomly divided into sepsis (n = 6) or sham (n = 6) groups, and then the whole brain tissue was dissected at 24 h after surgery for further protein identification by TMT-LC–MS/MS-based proteomics. Ingenuity pathway analysis, Gene ontology knowledgebase, and STRING database are used to explore the biological significance of proteins with altered concentration. Results: Among the total of 3163 proteins identified in the brain tissue, 57 were increased while 38 were decreased in the sepsis group compared to the sham group. Bioinformatic analyses suggest that the differentially abundant proteins are highly related to cellular microtubule metabolism, energy production, nucleic acid metabolism, neurological disease, etc. Additionally, acute phase response signaling was possibly activated and PI3K/AKT signaling was suppressed during sepsis. An interaction network established by IPA revealed that Akt1, Gc-globulin, and ApoA1 were the core proteins. The increase of Gc-globulin and the decrease of Akt1 were confirmed by Western blot. Conclusions: Based on the multifunction of these proteins in several brain diseases, we first propose that Gc-globulin, ApoA1, PI3K/AKT pathway, and acute phase response proteins (hemopexin and cluster of alpha-2-macroglobulin) can potentially be diagnosis biomarkers, therapeutic targets, and prognosis indicators of SAE. These results may provide new insights into the pathologic mechanism of SAE, yet further research is required to explore the functional implications and clinical applications of the differentially abundant proteins in the brains of sepsis group.

Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.

Project description:Ethnopharmacological relevance: Gubenfangxiao decoction (GBFXD) is a traditional Chinese medicine formula derived from Yupingfensan, an ancient formula widely used to treat respiratory diseases such as repeated respiratory infection, allergic rhinitis, bronchitis, and asthma. In recent years, GBFXD has been applied to efficaciously and safely treat asthma. However, the mechanism of GBFXD is still not fully elucidated. Aim of the study: A label-free proteomic method was to employed to explore the protective mechanism of GBFXD in respiratory syncytial virus (RSV)-ovalbumin (OVA)-induced chronic persistent asthmatic mice. Materials and methods: After RSV-OVA challenge, mice were orally administered GBFXD at a dose of 36 g/kg/d accompanied with OVA nasal spray once every 3 days for 28 days. The label-free proteomics-based liquid chromatography-tandem mass spectrometry method was used to explore the differentially abundant proteins (DAPs) in the serum from model mice compared with that in control mice (M:C), and in GBFXD-treated mice compared with that in model mice (G:M). We utilized OmicsBean (http://www.omicsbean.cn), a multi-omics data analysis platform, to perform bioinformatics analysis of DAPs. Enzyme-linked immunosorbent assay and Western Blotting were performed to measure the levels of related proteins and verify the results of proteomics analysis. Results: A total of 69 significant DAPs were identified including 39 in M:C, 46 in G:M, and 16 common differential proteins. Bioinformatics analysis revealed that the DAPs of M:C were mainly involved in inflammatory response and were related to lipid metabolism. However, the DAPs of G:M mostly participated in stress response, inflammatory response, and epithelial cell proliferation. Serum levels of Apoa-1, Apoc-1, Cfd, and Lrg1, EGFR and Lrg1 in the lungs were consistent with the results of proteomic analysis. Apoa-1 and Apoc-1 are closely related to cholesterol transport, lipid metabolism balance, and airway epithelial integrity; Cfd participates in immune response, affecting the occurrence and development of inflammation; EGFR and Lrg1 are involved in epithelial cell proliferation, influencing the process of airway remodeling. Conclusions: GBFXD may affect inflammatory and immune responses of asthma by regulating cholesterol transport and complement factor activation. Furthermore, it could repair damaged airway epithelium and avoid airway remodeling to prevent and treat asthma.

Dataset Information

Serum protein profile in LPS-induced mice model by two-dimensional LC-MS/MS

Publications

Apolipoprotein A-V Is a Novel Diagnostic and Prognostic Predictor in Pediatric Patients with Sepsis: A Prospective Pilot Study in PICU.

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