Lachnospiraceae-bacterium alleviates ischemia-reperfusion injury in steatotic donor liver by inhibiting ferroptosis via the Foxo3-Alox15 signaling pathway

Gut Microbes, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 30, 2025

Ischemia-reperfusion injury (IRI) is a major obstacle in liver transplantation, especially with steatotic donor livers. Dysbiosis of the gut microbiota has been implicated modulating IRI, and Lachnospiraceae plays pivotal role regulating host inflammatory immune responses, but its specific transplantation IRI remains unclear. This study explores whether can mitigate underlying mechanisms. We found Lachnospiraceae-bacterium (Lachn.) abundance was significantly reduced rats cirrhosis. Lachn.-treated exhibited improved intestinal permeability, severity both normal livers, decreased levels neutrophil macrophage infiltration, cytokines. Multi-omics analysis revealed elevated pyruvate transplanted livers after Lachn. treatment, alongside Alox15 Foxo3 expression. Mechanistically, Lachn.-derived inhibited expression ferroptosis Furthermore, nuclear translocation further suppressed expression, alleviating Clinical samples confirmed cirrhotic recipients high transplantation. In conclusion, alleviates by inhibiting via Foxo3-Alox15 axis, providing potential therapeutic strategy to modulate alleviate following

Язык: Английский

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Focusing on Ischemic Reperfusion Injury in the New Era of Dynamic Machine Perfusion in Liver Transplantation

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 1117 - 1117

Опубликована: Янв. 17, 2024

Liver transplantation is the most effective treatment for end-stage liver disease. Transplant indications have been progressively increasing, with a huge discrepancy between supply and demand of optimal organs. In this context, use extended criteria donor grafts has gained importance, even though these are more susceptible to ischemic reperfusion injury (IRI). Hepatic IRI an inherent inevitable consequence all transplants; it involves ischemia-mediated cellular damage exacerbated upon its severity directly affects graft function post-transplant complications. Strategies organ preservation constantly improving since they first emerged. The current gold standard perfusion solutions static cold storage. However, novel approaches that allow times, evaluation, their treatment, which could increase number viable organs transplantation, currently under investigation. This review discusses mechanisms associated IRI, describes existing strategies preservation, emphasizes developments challenges optimization.

Язык: Английский

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Validation of a Pretransplant Risk Prediction Model for Early Allograft Dysfunction After Living-donor Liver Transplantation

Transplantation, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Early allograft dysfunction (EAD) affects outcomes in liver transplantation (LT). Existing risk models developed for deceased-donor LT depend on posttransplant factors and fall short living-donor (LDLT), where pretransplant evaluations are crucial preventing EAD justifying the donor's risks. This retrospective study analyzed data from 2944 adult patients who underwent LDLT at 17 centers between 2016 2020. We a logistic regression model to predict based this development cohort. used 1020 King Faisal Transplant Center external validation. In cohort, 321 (10.9%) experienced EAD. These had poorer health status, more decompensation, higher requirements of hospitalization than those without Multivariable identified independent predictors EAD: laboratory Model End-Stage Liver Disease score (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.06-1.09), necessity time transplant (OR, 2.58; CI, 2.00-3.30), graft weight kilogram 0.27; 0.17-0.45). Using these predictors, we after LDLT, which demonstrated strong discriminative ability cohort with an area under curve (AUC) 0.71 (95% 0.68-0.74). The maintained high discrimination during internal validation (AUC, 0.70; 0.67-0.73) showed modest reduction power 0.65; 0.61-0.68). post-LDLT is influenced by recipient's condition weight. Integrating into process pairing donors recipients can enhance safety efficacy LDLT.

Язык: Английский

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Circadian Control of Hepatic Ischemia/Reperfusion Injury via HSD17B13-Mediated Autophagy in Hepatocytes

Journal of Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Dual-color reversible fluorescent carbon dots designed for dynamic monitoring of cellular superoxide anion radicals

Journal of Materials Chemistry B, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Synthesis of dual-color fluorescent CDs and schematic their dynamic reversible detection O 2 ˙ − .

Язык: Английский

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Insights into the Role of Glutathione Peroxidase 3 in Non-Neoplastic Diseases

Biomolecules, Год журнала: 2024, Номер 14(6), С. 689 - 689

Опубликована: Июнь 13, 2024

Reactive oxygen species (ROSs) are byproducts of normal cellular metabolism and play pivotal roles in various physiological processes. Disruptions the balance between ROS levels body’s antioxidant defenses can lead to development numerous diseases. Glutathione peroxidase 3 (GPX3), a key component system, is an oxidoreductase enzyme. GPX3 mitigates oxidative damage by catalyzing conversion hydrogen peroxide into water. Beyond its function, vital regulating metabolism, modulating cell growth, inducing apoptosis facilitating signal transduction. It also serves as significant tumor suppressor cancers. Recent studies have revealed aberrant expression several non-neoplastic diseases, associating it with multiple pathological This review synthesizes current understanding regulation, highlighting extensive noncancerous Additionally, this paper evaluates potential diagnostic biomarker explores emerging therapeutic strategies targeting enzyme, offering avenues for future clinical treatment conditions.

Язык: Английский

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Dexmedetomidine alleviates ferroptosis following hepatic ischemia-reperfusion injury by upregulating Nrf2/GPx4-dependent antioxidant responses

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 169, С. 115915 - 115915

Опубликована: Ноя. 24, 2023

Hepatic ischemia-reperfusion injury (HIRI) adversely affects liver transplant and resection outcomes. Recently, ferroptosis has been associated with HIRI. Dexmedetomidine (Dex), a potent sedative anti-inflammatory, antioxidant, anti-apoptotic properties, protects organs from hypoxic or (I/R) injuries. However, the mechanisms underlying this protective effect against I/R-induced remain unclear. This study evaluated of Dex on HIRI in mouse models oxygen-glucose deprivation/reperfusion (OGD/R) AML12 cell model. We examined ferroptosis-related markers, including Fe2+ levels, reactive oxygen species (ROS) content, mitochondrial morphology, GPX4 protein expression, 4-hydroxynonenal (4-HNE), Nrf2. The Nrf2 inhibitor ML385 was used combination to treat mice OGD/R-induced cellular explore pathways by which counteracts ferroptosis. Our results showed that treatment significantly ameliorated cells, reduced Fe2+, ROS, malondialdehyde (MDA), 4-HNE levels. also tissue damage serum AST, ALT, inflammatory factor levels mice. Additionally, increased GSH, an antioxidative stress marker, expression Mechanistically, nuclear translocation were inhibited both OGD/R-treated cells. restored inhibition translocation. Dex-promoted aggregation Gpx4 hindering efficacy Dex. In conclusion, ameliorates positively regulating Nrf2/GPx4 axis, potentially presenting therapeutic avenue for addressing

Язык: Английский

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New therapeutic concepts against ischemia-reperfusion injury in organ transplantation

Expert Review of Clinical Immunology, Год журнала: 2023, Номер 19(10), С. 1205 - 1224

Опубликована: Июль 25, 2023

Ischemia-reperfusion injury (IRI) involves a positive amplification feedback loop that stimulates innate immune-driven tissue damage associated with organ procurement from deceased donors and during transplantation surgery. As our appreciation of its basic immune mechanisms has improved in recent years, translating putative biomarkers into therapeutic interventions clinical remains challenging.

Язык: Английский

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Effects of remote ischemic preconditioning in hepatectomy: a systematic review and meta-analysis

BMC Anesthesiology, Год журнала: 2024, Номер 24(1)

Опубликована: Март 26, 2024

Abstract Background Animal experiments have confirmed that remote ischemic preconditioning (RIPC) can reduce hepatic ischemia-reperfusion injuries (HIRIs), significantly improving early tissue perfusion and oxygenation of the residual liver after resections, accelerating surgical prognoses, survival rates. However, there is still controversy over role RIPC in relieving HIRI clinical studies, which warrants clarification. This study aimed to evaluate beneficial effects applicability hepatectomy provide evidence-based information for decision-making. Methods Randomized controlled trials (RCTs) evaluating efficacy safety interventions were collected, comparing no patients undergoing hepatectomies. search spanned from database inception January 2024. Data extracted independently by two researchers according PRISMA guidelines. The primary outcomes assessed postoperative alanine transaminase (ALT), aspartate (AST), total bilirubin (TBIL), albumin (ALB) levels. secondary included duration surgery Pringle, length hospital stay, intraoperative blood loss transfusion, indocyanine green (ICG) clearance, hepatocyte apoptosis index, complications, others. Results Ten RCTs this meta-analysis, with a 865 (428 group 437 control group). ALT levels lower than those on day (POD) 1 (WMD = − 59.24, 95% CI: 115.04 3.45; P 0.04) POD 3 27.47, 52.26 2.68; 0.03). heterogeneities significant ( I 2 89% 78%), unstable based sensitivity analysis. AST 50.03, - 94.35 5.71; 0.03), but heterogeneity was also 81%). A subgroup analysis showed differences between groups, regardless whether Pringle maneuver or propofol used anesthesia (induction only induction maintenance, > 0.05). remaining outcome indicators not statistically could be analyzed due lack sufficient data. Conclusion has some short-term protective HIRIs during insufficient evidence encourage its routine use improve outcomes. Trial registration protocol registered PROSPERO (CRD42022333383).

Язык: Английский

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Sentrin-specific protease 1 maintains mitochondrial homeostasis through targeting the deSUMOylation of sirtuin-3 to alleviate oxidative damage induced by hepatic ischemia/reperfusion

Free Radical Biology and Medicine, Год журнала: 2023, Номер 210, С. 378 - 389

Опубликована: Дек. 3, 2023

Hepatic ischemia/reperfusion injury (HIRI) represents a prevalent pathophysiological process that imposes substantial economic burden in clinical practice, especially liver surgery. Sentrin-specific protease 1 (SENP1) is crucial enzyme involved the regulation of SUMOylation, and related to various diseases. However, role SENP1 HIRI remains unexplored. Here, we confirmed actively participated modulating oxidative damage induced by HIRI. Notably, functioned maintaining mitochondrial homeostasis. Further mechanistic exploration indicated protective protein sirtuin-3 (Sirt3) was inactivated SUMOylation during HIRI, which reversed SENP1. Overexpression could restore function, mitigate stress attenuated apoptosis through recovering expression Sirt3 Nevertheless, 3-TYP, an inhibitor Sirt3, eliminate therapeutic effects brought overexpression In conclusion, our findings demonstrated mediated deSUMOylation maintained homeostasis, thus alleviating damage. might be promising target for

Язык: Английский

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