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Proteomic profiling comparison for plasma from patients with acute ischemic stroke under rt-PA treatment

ABSTRACT: In this study, a total of 10 patients who received rt-PA were enrolled. Plasma samples were collected before and 1 hour after the rt-PA infusion for proteomic analysis. Blood sample collection has been approved by Tianjin Medical University General Hospital Ethics Committee, and collection was conducted according to the Declaration of Helsinki. Informed consent was obtained from all participants, and all experiments were conducted in accordance with Chinese laws and institutional guidelines.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Wei Jiang

LAB HEAD: Wei Jiang

PROVIDER: PXD046676 | Pride | 2024-07-12

REPOSITORIES: Pride

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			Action	DRS
	21P14410007.raw	Raw
	21P14410008.raw	Raw
	21P14410009.raw	Raw
	21P14410010.raw	Raw
	21P14410011.raw	Raw

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Proteomic profiling comparison for plasma from patients with acute ischemic stroke under rt-PA treatment

Project description:In this study, a total of 10 patients who received rt-PA were enrolled. Plasma samples were collected before and 1 hour after the rt-PA infusion for proteomic analysis. Blood sample collection has been approved by Tianjin Medical University General Hospital Ethics Committee, and collection was conducted according to the Declaration of Helsinki. Informed consent was obtained from all participants, and all experiments were conducted in accordance with Chinese laws and institutional guidelines.

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Proteomic profiling for isolated human peripheral blood neutrophils treated with HRG and tPA

Project description:In this study, neutrophils isolated from human peripheral blood were cultured with PBS, tPA(10μg/ml) or tPA+HRG (0.5μm) for 2.5 hours at 37 ° C . Then, neutrophils were collected for proteomic analysis (n=6). Blood sample collection has been approved by Tianjin Medical University General Hospital Ethics Committee, and collection was conducted according to the Declaration of Helsinki. Informed consent was obtained from all participants, and all experiments were conducted in accordance with Chinese laws and institutional guidelines.

2024-07-15 | PXD051719 | Pride

Proteomic characterization of hepatic expression signatures affected in ZHX2 liver conditional knockout mice

Project description:The liver has an exceptional capacity for regeneration which is crucial for maintaining liver function. Since transcriptional regulation of genes controlling metabolism and cell division is a hallmark of liver regeneration (LR), we investigated the role of Zinc-finger and homeboxes 2 (ZHX2), a transcription factor critical for regulating liver postnatal gene expression and hepatic lipid hemostasis, in LR. Our results show that hepatocyte-specific Zhx2 knockout (Zhx2-KOhep) enhances LR after 2/3 partial hepatectomy in mice. Proteomics assays revealed higher mitochondrial oxidative phosphorylation (OXPHOS) in Zhx2-KOhep mouse livers. Oxygen consumption rate (OCR) and ATP generation assays confirmed the enhanced OXPHOS in Zhx2-KOhep mouse livers and human hepatocytes with ZHX2 knockdown.

2023-10-17 | PXD027897 | Pride

DIA based proteome of maize leaves

Project description:DIA based proteome of maize leaves under osmotic stress

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Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics

Project description:Targeted protein degradation (TPD), as exemplified by proteolysis-targeting chimera (PROTAC), is a prominent paradigm in drug discovery. In this study, we applied conventional and novel PROTAC approaches to develop broad-spectrum antivirals (targeting key host factors for many different viruses) and virus-specific antivirals (targeting unique viral proteins). With respect to host-directed antivirals, we identified a small molecule degrader, FM-74-103, with pan-antiviral activities, as shown by inhibiting both RNA and DNA viruses. FM-74-103 elicits the selective degradation of human GSPT1, a translation termination factor, which further shuts down translation initiation. With respect to virus-specific antivirals, we developed viral RNA oligonucleotide-based bifunctional molecules (Destroyers). We provided proof-ofprinciple that RNA mimics of viral promoter sequences can be used as molecular glues to recruit viral polymerase (vPOL) and target it for degradation. Collectively, this study shows that TPD can be exploited to rationally design and develop the next generations of antivirals.

2023-06-15 | PXD042352 | Pride

Ceramide-dependent vesicle secretion modulates the integrated stress response in hematopoietic stem cells

Project description:Cellular crosstalk within the bone marrow niche maintains hematopoietic stem and progenitor cell (HSPC) integrity and safeguards lifelong blood and immune cell production. Deeper understanding of reciprocal niche signals governing crucial properties of HSPCs is relevant to the pathophysiology of blood disorders and improving HSPC transplantation. Extracellular vesicles (EVs) are key factors of the HSPC secretome, providing signals that regulate homeostasis and stemness. Here we demonstrate ex vivo blockade of ceramide-dependent vesicle secretion from HSPCs activates an integrated stress response (ISR), promoting downstream mTOR inhibition and metabolic quiescence. Crucially, ceramide-EV depletion leads to striking improvements in long-term transplantation. The aggregate findings link ceramide-dependent EV secretion and the ISR as a regulatory dyad guarding HSPC homeostasis and long-term fitness. Translationally, these data support exploration of ceramide inhibition during ex vivo maintenance of HSPCs for adoptive transfer.

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Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant

Project description:Here we use unbiased abundance proteomics and phosphoproteomics to assess global changes to host and viral proteins in Calu-3 cells at 10 and 24 hours post infection with either the B.1.1.7 UK variant or early-lineage SARS-CoV-2 viruses VIC and IC19.

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SARS-CoV-2 hijacks p38β/MAPK11 to promote virus replication

Project description:SARS-CoV-2, the causative agent of the COVID-19 pandemic, drastically modifies infected cells in an effort to optimize virus replication. Included in this process is the activation of the host p38 mitogen-activated protein kinase (MAPK) pathway, which plays a major role in inflammation and is a central driver of COVID-19 clinical presentations. Inhibition of p38/MAPK activity in SARS-CoV-2-infected cells reduces both cytokine production and viral replication. Here, we combined genetic screening with quantitative phosphoproteomics to better understand interactions between the p38/MAPK pathway and SARS-CoV-2. We found several components of the p38/MAPK pathway impact SARS-CoV-2 replication and that p38β is a critical host factor that promotes viral replication and prevents activation of the interferon pathway. Quantitative phosphoproteomics uncovered several SARS-CoV-2 nucleocapsid (N) protein phosphorylation sites near the N-terminus that were sensitive to p38 inhibition. Similar to p38β depletion, mutation of these N residues was associated with reduced viral replication and increased activation of Type I interferon signaling. Taken together, this study reveals a unique proviral function for p38β that is not shared with p38α, and supports efforts to develop p38β inhibitors as a strategy towards developing a new class of COVID-19 therapies. methods

2023-06-01 | PXD035451 | Pride

Integrated microRNA and secretome analysis of human endometrial organoid reveal the miR-3194-5p/Aquaporin/S100A9 module in regulating trophoblast functions

Project description:Successful placentation requires delicate communication between endometrium and trophoblasts. The invasion and integration of trophoblasts into the endometrium during early pregnancy is crucial to placentation. Dysregulation of these functions is associated with various pregnancy complications such as miscarriage and preeclampsia. The endometrial microenvironment exerts an important influence on trophoblast cell functions. We hypothesized that the hormonal environment regulates the miRNA profile and secretome of the human endometrial gland, which subsequently modulates trophoblast functions during early pregnancy. By establishing the first secretome profiles and miRNA atlas of these endometrial organoids to the hormonal changes followed by trophoblast functional assays, we demonstrated that sex steroid hormones modulate aquaporins (AQP)1/9 and S100A9 secretions through miR-3194 activation in endometrial epithelial cells, which in turn enhanced trophoblast migration and invasion during early pregnancy.

2023-05-10 | PXD036535 | Pride

Proteome Dynamics Reveals Pro-inflammatory Remodeling of Plasma Proteome in a Mouse Model of NAFLD

Project description:Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease (CVD). Liver is the major source of the circulatory proteins and alterations in plasma proteome have been implicated in atherosclerosis. We used a recently developed 2H2O-metabolic labeling method in combination with the label-free quantification to evaluate the effect of a Western diet (WD) on the dynamics of plasma proteins in LDL receptor-deficient (LDLR-/-) mice, a model of NAFLD and atherosclerosis. There were no significant changes in the expression level of total proteins due to the WD with a bulk protein mean half-life of 18.0±15.1 hours in control and 16.7±11.1 hours in WD groups. WD led to pro-inflammatory distribution of circulatory proteins analyzed in apoB-depleted plasma attributed to their increased production. The fractional catabolic rates of fast-turnover proteins with stress-response, lipid metabolism and transport functions were significantly increased with WD (P<0.05). The pathway analyses revealed that alterations in plasma proteome dynamics were related to the suppression of hepatic PPARα, which was confirmed based on reduced gene and protein expression of PPARα on WD. These changes were associated with ~4 fold increase (P<0.0001) in pro-inflammatory property of apoB-depleted plasma. In conclusion, the proteome dynamics method reveals pro-inflammatory remodeling of plasma proteome relevant to liver disease. As in vivo metrics of liver function, this approach can be used to test therapies in NAFLD and other diseases

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