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  1. Article: Binding and Kinetic Analysis of Human Protein Phosphatase PP2A Interactions with Caspase 9 Protein and the Interfering Peptide C9h.

    Dorgham, Karim / Murail, Samuel / Tuffery, Pierre / Savier, Eric / Bravo, Jeronimo / Rebollo, Angelita

    Pharmaceutics

    2022  Volume 14, Issue 10

    Abstract: The serine/threonine phosphatase PP2A and the cysteine protease Caspase 9 are two proteins involved in physiological and pathological processes, including cancer and apoptosis. We previously demonstrated the interaction between Caspase 9 and PP2A and ... ...

    Abstract The serine/threonine phosphatase PP2A and the cysteine protease Caspase 9 are two proteins involved in physiological and pathological processes, including cancer and apoptosis. We previously demonstrated the interaction between Caspase 9 and PP2A and identified the C9h peptide, corresponding to the binding site of Caspase 9 to PP2A. This interfering peptide can modulate Caspase 9/PP2A interaction leading to a strong therapeutic effect in vitro and in vivo in mouse models of tumor progression. In this manuscript, we investigate (I) the peptide binding to PP2A combining docking with molecular dynamics and (II) the secondary structure of the peptide using CD spectroscopy. Additionally, we compare the binding affinity, using biolayer interferometry, of the wild-type protein PP2A with Caspase 9 and vice versa to that observed between the PP2A protein and the interfering peptide C9h. This result strongly encourages the use of peptides as new therapeutics against cancer, as shown for the C9h peptide already in clinical trial.
    Language English
    Publishing date 2022-09-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics14102055
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  2. Article ; Online: Atypical White Matter Hyperintensities Markedly Impact Plasma Neurofilament Light Chain Variability in GRN Patients.

    Vítor, Joana / Saracino, Dario / Ströer, Sebastian / Camuzat, Agnès / Dorgham, Karim / Clot, Fabienne / Martin-Hardy, Philippe / Pasquier, Florence / Le Ber, Isabelle

    Journal of Alzheimer's disease : JAD

    2023  Volume 94, Issue 4, Page(s) 1351–1360

    Abstract: GRN mutations, causing frontotemporal dementia, can be associated with atypical white matter hyperintensities (WMH). We hypothesized that the presence of WMH may impact neurofilament light chain (NfL) levels, markers of neuroaxonal damage. We analyzed ... ...

    Abstract GRN mutations, causing frontotemporal dementia, can be associated with atypical white matter hyperintensities (WMH). We hypothesized that the presence of WMH may impact neurofilament light chain (NfL) levels, markers of neuroaxonal damage. We analyzed plasma NfL in 20 GRN patients and studied their association to visually-scored WMH burden. The 12 patients displaying atypical WMH had significantly higher NfL levels (98.4±34.9 pg/mL) than those without WMH (47.2±29.4 pg/mL, p = 0.003), independently from age, disease duration and Fazekas-Schmidt grade. NfL correlated with WMH burden (rho = 0.55, p = 0.01). This study prompts considering WMH burden as a variability factor when evaluating NfL levels in GRN patients.
    MeSH term(s) Humans ; Biomarkers ; Frontotemporal Dementia/genetics ; Intermediate Filaments ; Mutation ; Neurofilament Proteins ; Progranulins/genetics ; White Matter/diagnostic imaging
    Chemical Substances Biomarkers ; GRN protein, human ; Neurofilament Proteins ; Progranulins ; neurofilament protein L
    Language English
    Publishing date 2023-06-23
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-230315
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  3. Article ; Online: Tocilizumab in COVID-19 therapy: who benefits, and how?

    Neumann, Avidan U / Goekkaya, Mehmet / Dorgham, Karim / Traidl-Hoffmann, Claudia / Gorochov, Guy

    Lancet (London, England)

    2021  Volume 398, Issue 10297, Page(s) 299–300

    MeSH term(s) Antibodies, Monoclonal, Humanized ; COVID-19/drug therapy ; Humans ; SARS-CoV-2
    Chemical Substances Antibodies, Monoclonal, Humanized ; tocilizumab (I031V2H011)
    Language English
    Publishing date 2021-07-22
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(21)01427-6
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  4. Article ; Online: Longitudinal Cytokine Profiling in Patients with Severe COVID-19 on Extracorporeal Membrane Oxygenation and Hemoadsorption.

    Lebreton, Guillaume / Dorgham, Karim / Quentric, Paul / Combes, Alain / Gorochov, Guy / Schmidt, Matthieu

    American journal of respiratory and critical care medicine

    2021  Volume 203, Issue 11, Page(s) 1433–1435

    MeSH term(s) Biomarkers/blood ; COVID-19/blood ; COVID-19/epidemiology ; COVID-19/therapy ; Cytokines/blood ; Extracorporeal Membrane Oxygenation/methods ; Humans ; Plasmapheresis/methods ; SARS-CoV-2
    Chemical Substances Biomarkers ; Cytokines
    Language English
    Publishing date 2021-03-16
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.202011-4140LE
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  5. Article ; Online: Considering Personalized Interferon Beta Therapy for COVID-19.

    Dorgham, Karim / Neumann, Avidan U / Decavele, Maxens / Luyt, Charles-Edouard / Yssel, Hans / Gorochov, Guy

    Antimicrobial agents and chemotherapy

    2021  Volume 65, Issue 4

    MeSH term(s) COVID-19 ; Humans ; Interferon beta-1a ; Lopinavir ; Ritonavir ; SARS-CoV-2
    Chemical Substances Lopinavir (2494G1JF75) ; Ritonavir (O3J8G9O825) ; Interferon beta-1a (XRO4566Q4R)
    Language English
    Publishing date 2021-03-18
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.00065-21
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    Einzelsignatur: Show issues

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  6. Article ; Online: Beneficial role of Pistacia lentiscus aqueous extract in experimental colitis: anti-inflammatory and potential therapeutic effects.

    Boutemine, Insaf-Meriem / Amri, Manel / Dorgham, Karim / Amir, Zine-Charaf / Benazzouz, Sara / Ameur, Fahima / Layaida, Karim / Yssel, Hans / Touil-Boukoffa, Chafia

    Inflammopharmacology

    2021  Volume 29, Issue 4, Page(s) 1225–1239

    Abstract: Background: Pistacia lentiscus L. (PL) is a flowering plant traditionally used in the treatment of gastrointestinal disorders. The extracts of this plant are endowed with strong pharmacological activities. The aim of our current study was to investigate ...

    Abstract Background: Pistacia lentiscus L. (PL) is a flowering plant traditionally used in the treatment of gastrointestinal disorders. The extracts of this plant are endowed with strong pharmacological activities. The aim of our current study was to investigate the anti-inflammatory and potential therapeutic effects of PL leaves aqueous extract (PLAE) against Dextran Sulfate Sodium (DSS)-induced acute colitis.
    Materials and methods: The therapeutic effect of PLAE was evaluated after orally administration of 3% DSS alone or concomitantly with PLAE (50, 100 or 200 mg/Kg). Mucosal lesions were assessed by macroscopic and histopathological examination. In this context, hemorrhage, diarrhea, weight loss, and disease activity index (DAI) were determined daily throughout the experiment. In the same way, hematoxylin-eosin and Alcian blue staining of colonic mucosal were used to evaluate, respectively, mucosal damages and mucus production. Furthermore, the levels of nitric oxide (NO), and pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] were measured in plasma, as well as in colonic explants and peritoneal macrophages cultures supernatants.
    Results: Administration of DSS + PLAE indicated a significant reduction in clinical score of acute colitis DAI compared to DSS alone administration. Interestingly, histological analysis of the mucosa showed that DSS + PLAE-treated groups exhibited almost normal histology evidenced by an intact epithelium structure and less inflammatory cell infiltration in the mucosa. Alcian bleu staining revealed that DSS + PLAE-treated groups displayed almost normal mucus production. Importantly, a significant decrease in pro-inflammatory mediators (NO, IL-6 and TNF-α) levels in dose-dependent manner was reported in plasma, and culture supernatants of colonic explants and peritoneal macrophages from DSS + PLAE-treated mice compared to the DSS group.
    Conclusion: Our results showed that the systemic and local anti-inflammatory activities of aqueous leaves extract of PL improve the clinical signs of acute colitis. Our data suggest that PLAE has beneficial effects and could constitute a promising approach against acute ulcerative colitis by targeting the deregulated immune response.
    MeSH term(s) Animals ; Anti-Inflammatory Agents/isolation & purification ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Proliferation/physiology ; Cells, Cultured ; Colitis/chemically induced ; Colitis/drug therapy ; Colitis/metabolism ; Dextran Sulfate/toxicity ; Dose-Response Relationship, Drug ; Female ; Mice ; Mice, Inbred BALB C ; Pistacia ; Plant Extracts/isolation & purification ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Treatment Outcome ; Water
    Chemical Substances Anti-Inflammatory Agents ; Plant Extracts ; Water (059QF0KO0R) ; Dextran Sulfate (9042-14-2)
    Language English
    Publishing date 2021-06-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1080058-x
    ISSN 1568-5608 ; 0925-4692
    ISSN (online) 1568-5608
    ISSN 0925-4692
    DOI 10.1007/s10787-021-00831-w
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  7. Article ; Online: Cytokines in New-Onset Refractory Status Epilepticus Predict Outcomes.

    Hanin, Aurélie / Cespedes, Jorge / Dorgham, Karim / Pulluru, Yashwanth / Gopaul, Margaret / Gorochov, Guy / Hafler, David A / Navarro, Vincent / Gaspard, Nicolas / Hirsch, Lawrence J

    Annals of neurology

    2023  Volume 94, Issue 1, Page(s) 75–90

    Abstract: Objective: The objective of this study was to investigate inflammation using cerebrospinal fluid (CSF) and serum cytokines/chemokines in patients with new-onset refractory status epilepticus (NORSE) to better understand the pathophysiology of NORSE and ... ...

    Abstract Objective: The objective of this study was to investigate inflammation using cerebrospinal fluid (CSF) and serum cytokines/chemokines in patients with new-onset refractory status epilepticus (NORSE) to better understand the pathophysiology of NORSE and its consequences.
    Methods: Patients with NORSE (n = 61, including n = 51 cryptogenic), including its subtype with prior fever known as febrile infection-related epilepsy syndrome (FIRES), were compared with patients with other refractory status epilepticus (RSE; n = 37), and control patients without SE (n = 52). We measured 12 cytokines/chemokines in serum or CSF samples using multiplexed fluorescent bead-based immunoassay detection. Cytokine levels were compared between patients with and without SE, and between the 51 patients with cryptogenic NORSE (cNORSE) and the 47 patients with a known-etiology RSE (NORSE n = 10, other RSE n = 37), and correlated with outcomes.
    Results: A significant increase of IL-6, TNF-α, CXCL8/IL-8, CCL2, MIP-1α, and IL-12p70 pro-inflammatory cytokines/chemokines was observed in patients with SE compared with patients without SE, in serum and CSF. Serum innate immunity pro-inflammatory cytokines/chemokines (CXCL8, CCL2, and MIP-1α) were significantly higher in patients with cNORSE compared to non-cryptogenic RSE. Patients with NORSE with elevated innate immunity serum and CSF cytokine/chemokine levels had worse outcomes at discharge and at several months after the SE ended.
    Interpretation: We identified significant differences in innate immunity serum and CSF cytokine/chemokine profiles between patients with cNORSE and non-cryptogenic RSE. The elevation of innate immunity pro-inflammatory cytokines in patients with NORSE correlated with worse short- and long-term outcomes. These findings highlight the involvement of innate immunity-related inflammation, including peripherally, and possibly of neutrophil-related immunity in cNORSE pathogenesis and suggest the importance of utilizing specific anti-inflammatory interventions. ANN NEUROL 2023;94:75-90.
    MeSH term(s) Humans ; Cytokines/cerebrospinal fluid ; Chemokine CCL3 ; Status Epilepticus/diagnosis ; Chemokines ; Inflammation/complications
    Chemical Substances Cytokines ; Chemokine CCL3 ; Chemokines
    Language English
    Publishing date 2023-03-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80362-5
    ISSN 1531-8249 ; 0364-5134
    ISSN (online) 1531-8249
    ISSN 0364-5134
    DOI 10.1002/ana.26627
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  8. Article ; Online: Reply.

    Mathian, Alexis / Mouries-Martin, Suzanne / Dorgham, Karim / Yssel, Hans / Amoura, Zahir

    Arthritis & rheumatology (Hoboken, N.J.)

    2019  Volume 72, Issue 1, Page(s) 197

    MeSH term(s) Enzyme-Linked Immunosorbent Assay ; Humans ; Interferon-alpha ; Lupus Erythematosus, Systemic
    Chemical Substances Interferon-alpha
    Language English
    Publishing date 2019-11-23
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2756371-6
    ISSN 2326-5205 ; 2326-5191
    ISSN (online) 2326-5205
    ISSN 2326-5191
    DOI 10.1002/art.41094
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  9. Article ; Online: Serum interferon-α levels and IFN type I-stimulated genes score perform equally to assess systemic lupus erythematosus disease activity.

    Chasset, François / Mathian, Alexis / Dorgham, Karim / Ribi, Camillo / Trendelenburg, Marten / Huynh-Do, Uyen / Roux-Lombard, Pascale / Courvoisier, Delphine Sophie / Amoura, Zahir / Gorochov, Guy / Chizzolini, Carlo

    Annals of the rheumatic diseases

    2022  Volume 81, Issue 6, Page(s) 901–903

    MeSH term(s) Humans ; Interferon Type I ; Interferon-alpha ; Lupus Erythematosus, Systemic/genetics
    Chemical Substances Interferon Type I ; Interferon-alpha
    Language English
    Publishing date 2022-01-28
    Publishing country England
    Document type Research Support, Non-U.S. Gov't ; Letter
    ZDB-ID 7090-7
    ISSN 1468-2060 ; 0003-4967
    ISSN (online) 1468-2060
    ISSN 0003-4967
    DOI 10.1136/annrheumdis-2021-221835
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  10. Article ; Online: JAK inhibitors for the treatment of adult dermatomyositis: A pilot study.

    Landon-Cardinal, Océane / Guillaume-Jugnot, Perrine / Toquet, Ségolène / Sbeih, Nabiha / Rigolet, Aude / Champtiaux, Nicolas / Dorgham, Karim / Gorochov, Guy / Meyer, Alain / Anquetil, Céline / Barete, Stéphane / Benveniste, Olivier / Allenbach, Yves

    Journal of the American Academy of Dermatology

    2022  Volume 88, Issue 4, Page(s) 924–926

    MeSH term(s) Humans ; Adult ; Dermatomyositis/drug therapy ; Janus Kinase Inhibitors/therapeutic use ; Pilot Projects
    Chemical Substances Janus Kinase Inhibitors
    Language English
    Publishing date 2022-11-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603641-7
    ISSN 1097-6787 ; 0190-9622
    ISSN (online) 1097-6787
    ISSN 0190-9622
    DOI 10.1016/j.jaad.2022.10.055
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