ORCID Profile
0000-0002-7727-9893
Current Organisations
University of Jordan
,
Centre de Recherche Saint-Antoine
,
Université Paris-Sorbonne
,
INSERM
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Publisher: Springer Science and Business Media LLC
Date: 15-11-2018
Publisher: MDPI AG
Date: 18-08-2020
DOI: 10.3390/IJMS21165931
Abstract: While liver transplantation remains the sole treatment option for patients with end-stage liver disease, there are numerous limitations to liver transplantation including the scarcity of donor livers and a rise in livers that are unsuitable to transplant such as those with excess steatosis. Fatty livers are susceptible to ischaemia-reperfusion (IR) injury during transplantation and IR injury results in primary graft non-function, graft failure and mortality. Recent studies have described new cell death pathways which differ from the traditional apoptotic pathway. Necroptosis, a regulated form of cell death, has been associated with hepatic IR injury. Receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL) are thought to be instrumental in the execution of necroptosis. The study of hepatic necroptosis and potential therapeutic approaches to attenuate IR injury will be a key factor in improving our knowledge regarding liver transplantation with fatty donor livers. In this review, we focus on the effect of hepatic steatosis during liver transplantation as well as molecular mechanisms of necroptosis and its involvement during liver IR injury. We also discuss the immune responses triggered during necroptosis and examine the utility of necroptosis inhibitors as potential therapeutic approaches to alleviate IR injury.
Publisher: SAGE Publications
Date: 2023
DOI: 10.1177/17455057221150099
Abstract: The coronavirus disease 2019 pandemic has been an extraordinarily stressful situation in recent years. Stress is a physiological reaction to negative stimuli that is regulated by different neuroendocrine pathways. The female reproductive function is maintained by the menstrual cycle, which is negatively affected by hyperstimulation of stress signals. This study evaluates the effect of the coronavirus disease 2019 outbreak on menstrual function and mental health, exploring the relationship between them. The current study uses a cross-sectional, survey-based design. During this cross-sectional study, an online self-completion questionnaire was conducted among a s le of 385 Jordanian female medical students during the pandemic. The survey compared menstrual characteristics, depression, anxiety, and stress 10 months after the coronavirus disease 2019 pandemic with 10 months prior. Paired t-test, McNemar’s test, Pearson’s correlation, and multiple linear regression model were employed to analyze data using SPSS software. The mean age of female medical student respondents was 19.89 years. Data showed that the menstrual cycle length significantly increased during the coronavirus disease 2019 pandemic compared with 10 months prior (32.23 days versus 30.02 days, p = 0.019). The average number of heavy bleeding days also increased during the coronavirus disease 2019 pandemic (2.82 days versus 2.42 days, p = 0.002). The proportion of females with heavy bleeding amount was more than doubled during the pandemic of coronavirus disease 2019 compared with before (27.3% versus 10.4%, p = 0.000). Unpleasant menstrual signs such as nausea and/or vomiting, breast pain, and urinary urgency were significantly increased during the pandemic ( p = 0.000, p = 0.008, and p = 0.024, respectively). During coronavirus disease 2019, a positive association between total Depression, Anxiety, and Stress Scale-21 Questionnaire score and heavy bleeding was identified ( p 0.05). The findings also indicated that mental disorders and the incidence of amenorrhea, nausea and/or vomiting, and urinary urgency were positively correlated during the coronavirus disease 2019 pandemic. The multiple regression analysis revealed associations between several menstrual characteristics such as amenorrhea and severity of bleeding with coronavirus disease 2019-related depression, anxiety, and stress. This study revealed that the stress related to the pandemic of coronavirus disease 2019 could affect the female menstrual cycle and hence the quality of women’s life. Therefore, this study could serve as a baseline for planning and introducing stress mitigation interventions in crisis situations to improve the physiological and mental well-being of females and improve their quality of life.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.CCELL.2016.11.009
Abstract: Receptor-interacting protein kinase 1 (RIPK1) represents an essential signaling node in cell death and inflammation. Ablation of Ripk1 in liver parenchymal cells (LPC) did not cause a spontaneous phenotype, but led to tumor necrosis factor (TNF)-dependent hepatocyte apoptosis and liver injury without affecting inducible nuclear factor κB (NF-κB) activation. Loss of Ripk1 induced the TNF-dependent proteasomal degradation of the E3-ligase, TNF receptor-associated factor 2 (TRAF2), in a kinase-independent manner, thereby activating caspase-8. Moreover, loss of both Ripk1 and Traf2 in LPC not only resulted in caspase-8 hyperactivation but also impaired NF-κB activation, promoting the spontaneous development of hepatocellular carcinoma. In line, low RIPK1 and TRAF2 expression in human HCCs was associated with an unfavorable prognosis, suggesting that RIPK1 collaborates with TRAF2 to inhibit murine and human hepatocarcinogenesis.
Publisher: MDPI AG
Date: 08-01-2021
DOI: 10.3390/JCM10020212
Abstract: Background: Steatosis in donor livers poses a major risk of organ dysfunction due to their susceptibility to ischaemia-reperfusion (I/R) injury during transplant. Necroptosis, a novel form of programmed cell death, is orchestrated by receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL), has been implicated in I/R injury. Here we investigated the mechanisms of cell death pathways in an in vitro model of hepato-steatotic ischaemia. Methods: Free fatty acid (FFA) treated alpha mouse liver 12 (AML-12) cells were incubated in oxygen-glucose-deprivation (OGD) conditions as seen during ischaemia. Results: We found that OGD triggered upregulation of insoluble fraction of RIPK3 and MLKL in FFA + OGD cells compared to FFA control cells. We report that intervention with small interfering (si) MLKL and siRIPK3 significantly attenuated cell death in FFA + OGD cells. Absence of activated CASPASE8 and cleaved-CASPASE3, no change in the expression of CASPASE1 and prostaglandin-endoperoxide synthase 2 (Ptgs2) in FFA + OGD treated cells compared to FFA control cells indicated that apoptosis, pyroptosis and ferroptosis, respectively, are unlikely to be active in this model. Conclusion: Our findings indicate that RIPK3-MLKL dependent necroptosis contributed to cell death in our in vitro model. Both MLKL and RIPK3 are promising therapeutic targets to inhibit necroptosis during ischaemic injury in fatty liver.
No related grants have been discovered for Jérémie Gautheron.