Graphene oxide activates B cells with upregulation of granzyme B expression: evidence at the single-cell level for its immune-modulatory properties and anticancer activity

Orecchioni, Marco; Fusco, Laura; Mall, Raghvendra; Bordoni, Valentina; Fuoco, Claudia; Rinchai, Darawan; Guo, Shi; Sainz, Ricardo Calle; Zoccheddu, Martina; Gürcan, Cansu; Yılmazer, Açelya; Zavan, Barbara; Ménard‐Moyon, Cécilia; Bianco, Alberto; Hendrickx, Wouter; Bedognetti, Davide; Delogu, Lucia Gemma

doi:10.1039/d1nr04355b

Cited by 12 publications

(7 citation statements)

References 58 publications

(72 reference statements)

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“…The mRNAs which were identified to be regulated by the differentially expressed miRNAs were then utilized in an overexpression analysis framework. We used the ConsensusPathDB (29) web portal (http://cpdb.molgen.mpg.de/) as utilized in (30)(31)(32)(33)(34) to identify significantly enriched pathways choosing the PID (http://pid.nci.nih.gov/) and KEGG (https:// www.genome.jp/kegg/pathway.html) database. We also used the ConsensusPathDB web-portal to determine the significantly enriched GO terms.…”

Section: Pathway Enrichment Analysismentioning

confidence: 99%

Characteristic MicroRNAs Linked to Dysregulated Metabolic Pathways in Qatari Adult Subjects With Obesity and Metabolic Syndrome

Mir¹,

Mall²,

Iskandarani³

et al. 2022

Front. Endocrinol.

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BackgroundObesity-associated dysglycemia is associated with metabolic disorders. MicroRNAs (miRNAs) are known regulators of metabolic homeostasis. We aimed to assess the relationship of circulating miRNAs with clinical features in obese Qatari individuals.MethodsWe analyzed a dataset of 39 age-matched patients that includes 18 subjects with obesity only (OBO) and 21 subjects with obesity and metabolic syndrome (OBM). We measured 754 well-characterized human microRNAs (miRNAs) and identified differentially expressed miRNAs along with their significant associations with clinical markers in these patients.ResultsA total of 64 miRNAs were differentially expressed between metabolically healthy obese (OBO) versus metabolically unhealthy obese (OBM) patients. Thirteen out of 64 miRNAs significantly correlated with at least one clinical trait of the metabolic syndrome. Six out of the thirteen demonstrated significant association with HbA1c levels; miR-331-3p, miR-452-3p, and miR-485-5p were over-expressed, whereas miR-153-3p, miR-182-5p, and miR-433-3p were under-expressed in the OBM patients with elevated HbA1c levels. We also identified, miR-106b-3p, miR-652-3p, and miR-93-5p that showed a significant association with creatinine; miR-130b-5p, miR-363-3p, and miR-636 were significantly associated with cholesterol, whereas miR-130a-3p was significantly associated with LDL. Additionally, miR-652-3p’s differential expression correlated significantly with HDL and creatinine.ConclusionsMicroRNAs associated with metabolic syndrome in obese subjects may have a pathophysiologic role and can serve as markers for obese individuals predisposed to various metabolic diseases like diabetes.

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Section: Pathway Enrichment Analysismentioning

confidence: 99%

Characteristic MicroRNAs Linked to Dysregulated Metabolic Pathways in Qatari Adult Subjects With Obesity and Metabolic Syndrome

Mir¹,

Mall²,

Iskandarani³

et al. 2022

Front. Endocrinol.

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“…Using T and B lymphocytes isolated from the spleen of BALB/C mice, Murera et al found that FLG neither impacted viability nor activation of the cells. In more recent work, amino-functionalized GO sheets were compared to GO using primary human B lymphocytes . The authors found that GO-NH 2 , in particular, triggered B cell receptor activation and upregulation of granzyme B, an important cytotoxic protein, at 50 μg/mL.…”

Section: D Materials and Adaptive Immunitymentioning

confidence: 99%

Environmental and Health Impacts of Graphene and Other Two-Dimensional Materials: A Graphene Flagship Perspective

Lin,

Buerki-Thurnherr,

Kaur

et al. 2024

ACS Nano

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Two-dimensional (2D) materials have attracted tremendous interest ever since the isolation of atomically thin sheets of graphene in 2004 due to the specific and versatile properties of these materials. However, the increasing production and use of 2D materials necessitate a thorough evaluation of the potential impact on human health and the environment. Furthermore, harmonized test protocols are needed with which to assess the safety of 2D materials. The Graphene Flagship project (2013−2023), funded by the European Commission, addressed the identification of the possible hazard of graphene-based materials as well as emerging 2D materials including transition metal dichalcogenides, hexagonal boron nitride, and others. Additionally, socalled green chemistry approaches were explored to achieve the goal of a safe and sustainable production and use of this fascinating family of nanomaterials. The present review provides a compact survey of the findings and the lessons learned in the Graphene Flagship.

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“…To this end, we treated human peripheral blood mononuclear cells (PBMCs) with increasing concentrations (25, 50, and 100 μg mL −1 ) of V 4 C 3 or Ti 3 C 2 for 24 h, selecting this incubation time based on previous studies with other nanomaterials on immune cells. [14,[66][67][68][69][70][71][72][73][74][75][76][77] We used EtOH as a positive control. Subsequently, we stained cells with Fixable Viability Staining 780 and analyzed the effect of material exposure by flow cytometry, observing no reduction of PBMC viability (Figure S1B, Supporting Information).…”

Section: Hemocompatibility and Immunocompatibility Of V 4 C 3 Mxenementioning

confidence: 99%

V₄C₃ MXene Immune Profiling and Modulation of T Cell‐Dendritic Cell Function and Interaction

Fusco,

Gazzi,

Shuck

et al. 2023

Small Methods

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Although vanadium‐based metallodrugs are recently explored for their effective anti‐inflammatory activity, they frequently cause undesired side effects. Among 2D nanomaterials, transition metal carbides (MXenes) have received substantial attention for their promise as biomedical platforms. It is hypothesized that vanadium immune properties can be extended to MXene compounds. Therefore, vanadium carbide MXene (V4C3) is synthetized, evaluating its biocompatibility and intrinsic immunomodulatory effects. By combining multiple experimental approaches in vitro and ex vivo on human primary immune cells, MXene effects on hemolysis, apoptosis, necrosis, activation, and cytokine production are investigated. Furthermore, V4C3 ability is demonstrated to inhibit T cell‐dendritic cell interactions, evaluating the modulation of CD40–CD40 ligand interaction, two key costimulatory molecules for immune activation. The material biocompatibility at the single‐cell level on 17 human immune cell subpopulations by single‐cell mass cytometry is confirmed. Finally, the molecular mechanism underlying V4C3 immune modulation is explored, demonstrating a MXene‐mediated downregulation of antigen presentation‐associated genes in primary human immune cells. The findings set the basis for further V4C3 investigation and application as a negative modulator of the immune response in inflammatory and autoimmune diseases.

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Graphene oxide activates B cells with upregulation of granzyme B expression: evidence at the single-cell level for its immune-modulatory properties and anticancer activity

Abstract: While both graphene oxide and amino functionalized graphene oxide exert strong pro-activating properties on B cells, the latter is also able to induce a B cell receptor signaling dysregulation, which triggers the production of granzyme B.

Cited by 12 publications

References 58 publications

Characteristic MicroRNAs Linked to Dysregulated Metabolic Pathways in Qatari Adult Subjects With Obesity and Metabolic Syndrome

Characteristic MicroRNAs Linked to Dysregulated Metabolic Pathways in Qatari Adult Subjects With Obesity and Metabolic Syndrome

Environmental and Health Impacts of Graphene and Other Two-Dimensional Materials: A Graphene Flagship Perspective

V₄C₃ MXene Immune Profiling and Modulation of T Cell‐Dendritic Cell Function and Interaction

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Graphene oxide activates B cells with upregulation of granzyme B expression: evidence at the single-cell level for its immune-modulatory properties and anticancer activity

Abstract: While both graphene oxide and amino functionalized graphene oxide exert strong pro-activating properties on B cells, the latter is also able to induce a B cell receptor signaling dysregulation, which triggers the production of granzyme B.

Cited by 12 publications

References 58 publications

Characteristic MicroRNAs Linked to Dysregulated Metabolic Pathways in Qatari Adult Subjects With Obesity and Metabolic Syndrome

Characteristic MicroRNAs Linked to Dysregulated Metabolic Pathways in Qatari Adult Subjects With Obesity and Metabolic Syndrome

Environmental and Health Impacts of Graphene and Other Two-Dimensional Materials: A Graphene Flagship Perspective

V4C3 MXene Immune Profiling and Modulation of T Cell‐Dendritic Cell Function and Interaction

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V₄C₃ MXene Immune Profiling and Modulation of T Cell‐Dendritic Cell Function and Interaction