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Identification of immune-based biomarkers associated with response to abatacept (CTLA4-Ig) in rheumatoid arthritis patients.

ABSTRACT: RA patients (according to ACR/EULAR 2010 criteria) who started abatacept due to high disease activity (DAS28>5.1), were recruited to perform immunological studies at baseline, 3 and 6 months of therapy. Peripheral blood mononuclear cells (PBMCs) were isolated and immune cell populations were characterized using flow cytometry. Proteomic analysis was performed on baseline sera.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

DISEASE(S): Rheumatoid Arthritis

SUBMITTER: Martina Samiotaki

LAB HEAD: Prodromos Sidiropoulos

PROVIDER: PXD046112 | Pride | 2024-01-26

REPOSITORIES: Pride

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Publications

A Peripheral Blood Signature of Increased Th1 and Myeloid Cells Combined with Serum Inflammatory Mediators Is Associated with Response to Abatacept in Rheumatoid Arthritis Patients.

Goutakoli Panagiota P Papadaki Garyfalia G Repa Argyro A Avgoustidis Nestor N Kalogiannaki Eleni E Flouri Irini I Bertsias Antonios A Zoidakis Jerome J Samiotaki Martina M Bertsias George G Semitekolou Maria M Verginis Panayotis P Sidiropoulos Prodromos P

Cells 20231209 24

Abatacept (CTLA4-Ig)-a monoclonal antibody which restricts T cell activation-is an effective treatment for rheumatoid arthritis (RA). Nevertheless, only 50% of RA patients attain clinical responses, while predictors of response are rather limited. Herein, we aimed to investigate for early biomarkers of response to abatacept, based on a detailed immunological profiling of peripheral blood (PB) cells and serum proteins. We applied flow cytometry and proteomics analysis on PB immune cells and serum ...[more]

PMID: 38132128

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Transcriptome and proteome analysis reveals the anti-cancer properties of Hypnea musciformis macroalgae extract in liver and intestinal cancer cells

Project description:Hypnea musciformis is a red macroalga that is widely distributed in tropical and subtropical regions. It is known to contain various bioactive compounds, including sulfated polysaccharides, flavonoids, and phlorotannins. Recent studies have investigated the potential anticancer effects of extracts from Hypnea musciformis demonstrating their have cytotoxic effects on various cancer cell lines. The anticancer effects of these extracts are thought to be due to the presence of bioactive compounds, which have been shown to have antitumor and immunomodulatory effects. However, further studies are needed to fully understand the molecular mechanisms that underlie these anticancer effects and to determine their potential as therapeutic agents for cancer treatment. We have performed transcriptome and proteome analysis in liver and colon cancer human cell lines following treatment with Hypnea musciformis macroalgae extracts to characterize its anti-tumor effect in detail at the molecular level and to link transcriptome and proteome responses to the observed phenotypes in vitro. We have identified that treatment with the macroalgae extract triggers p53-mediated response at the transcriptional and protein level in liver cancer cells, in contrast to colon cancer cells in which the effects are associated with metabolic changes. Overall, the available evidence suggests that extracts from Hypnea musciformis have the potential to serve as a source of anticancer agents in liver cancer cells through the activation of a p53-mediated anti-tumor response that is linked to inhibition of cellular proliferation and induction of apoptosis.

2023-08-04 | PXD041686 | Pride

A novel method for isolation of spontaneously-released brain small extracellular vesicles

Project description:Extracellular vesicles (EVs), including small EVs (sEVs) such as exosomes, exhibit great potential for the diagnosis and treatment of brain disorders, representing an advantageous tool for Precision medicine. The latter demands high-quality human biospecimens, especially in complex disorders in which pathological and specimen heterogeneity as well diverse individual clinical profile often complicate the development of precision therapeutic schemes and patient-tailored treatments. Thus, the collection and characterization of physiologically relevant sEVs are of the utmost importance. However, standard brain EV isolation approaches rely on tissue dissociation, which can contaminate EV fractions with intracellular vesicles. Based on multiscale analytical platforms such as cryo-EM, label-free proteomics, advanced flow cytometry, and ExoView analyses, we hereby present an efficient purification method that captures a more physiologically relevant, small EV-enriched population spontaneously released by mouse and human brain tissue. The spontaneous release method of sEV yield may contribute to the characterization and biomarker profile of physiologically relevant brain-derived sEVs in brain function and pathology.

2023-03-11 | PXD031947 | Pride

Transcriptomic and proteomic profiling of non-classical monocytes unravels distinct pathogenic features in SLE

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Determination of the proteome of yeast cells during transition to quiescence

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2023-12-13 | PXD041191 | Pride

3'-tRF-CysGCA overexpression alters the expression profile of HEK-293 cells and modulates cellular processes and pathways

Project description:tRNA fragments (tRFs) are small non-coding RNA molecules that are generated through the cleavage of tRNAs and have been implicated in various biological processes. Among the different types of tRFs, the 3′-tRFs have attracted considerable scientific interest due to their regulatory role in gene expression. In this study, we investigated the role of 3′-tRF-CysGCA, a tRF derived from cleavage in the T-loop of tRNACysGCA, in the regulation of gene expression in HEK-293 cells. Previous studies have shown that 3′-tRF-CysGCA is incorporated into the RISC complex and interacts with Argonaute proteins, suggesting its involvement in the regulation of gene expression. However, the general role and effect of the deregulation of 3′-tRF-CysGCA levels in human cells have not been investigated so far. To address this gap, we stably overexpressed 3′-tRF-CysGCA in HEK-293 cells and performed transcriptomics and proteomics experiments. Moreover, we validated the interaction of this tRF with putative targets whose levels were affected after 3′-tRF-CysGCA overexpression. Last, we investigated the implication of 3′-tRF-CysGCA in various pathways using extensive bioinformatics analysis. Our results indicate that 3′-tRF-CysGCA overexpression led to changes in the cell expression profile, and we identified multiple pathways that were affected by the deregulation of this tRF. Additionally, our reporter assays demonstrated that 3′-tRF-CysGCA directly interacted with TMPO and ERGIC1, leading to changes in their expression levels. Taken together, these findings suggest that 3′-tRF-CysGCA plays a significant role in the regulation of gene expression and highlight the potential importance of this tRF in cellular processes.

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An Immunological Synapse Formation Between T Regulatory Cells and Cancer-Associated Fibroblasts Promotes Tumour Development

Project description:The cells were lysed in a buffer consisting of 4% SDS, 0.1 M DTT, 100 mM Tris/HCl; pH 7.6 and heated for 5 minutes at 99℃. The protein extracts were processed according to theSp3 protocol. The reduced cysteine residues were alkylated in 200 mM iodoacetamide (Acros Organics). 20 μg of beads (1:1 mixture of hydrophilic and hydrophobic SeraMag carboxylate-modified beads; GE Life Sciences) were added to each sample in 50% ethanol. Protein clean-up was performed on a magnetic rack. The beads were washed twice with 80% ethanol followed by one wash with 100% acetonitrile (Fisher Chemical). The beads-captured proteins were digested overnight at 37 ℃ with 0.5 μg trypsin/LysC mix in 25 mM ammonium bicarbonate under vigorous shaking (1200 rpm, Eppendorf Thermomixer). The supernatants were collected and the peptides were purified by a modified Sp3 clean-up protocol and finally solubilized in the mobile phase A (0.1% formic acid in water), and sonicated. Peptide concentration was determined through absorbance measurement at 280 nm using a nanodrop instrument.

2024-05-08 | PXD047024 | Pride

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The interactome of the UapA transporter reveals putative new players in anterograde membrane cargo trafficking: UapA-DYDY TurboID

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