Search Results (1,972)

Ocular ischemic syndrome (OIS) is a vision-threatening disorder characterized by retinal ischemia, oxidative stress, and inflammation. In this study, the protective effects of anakinra, an interleukin-1 receptor antagonist, were investigated and compared with those of tocilizumab, an interleukin-6 receptor antagonist. Twenty-four male Wistar rats were randomly assigned to four groups (n = 6 per group): sham-operated (SG), carotid artery clamping/unclamping (CUG), anakinra-treated carotid artery clamping/unclamping (ACUG), and tocilizumab-treated carotid artery clamping/unclamping (TCUG). An experimental ocular ischemic injury model induced by transient bilateral common carotid artery occlusion was established by transient bilateral common carotid artery clamping followed by reperfusion. Retinal tissues were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) levels, and histopathological examinations were performed. OIS markedly increased MDA, TNF-α, IL-1β, and IL-6 levels while significantly decreasing tGSH, SOD, and CAT activities. Both anakinra and tocilizumab attenuated oxidative stress and inflammatory responses; however, anakinra produced notably greater improvements in MDA, tGSH, SOD, and CAT levels. Histopathological evaluation demonstrated that both treatments reduced retinal injury, edema, vascular congestion, and inflammatory cell infiltration. Although retinal architecture appeared slightly better preserved in the anakinra-treated group, histopathological scores were comparable between the treatment groups. These findings suggest that anakinra may attenuate oxidative and inflammatory retinal damage in this experimental ocular ischemic injury model and may provide greater biochemical protection than tocilizumab, whereas histopathological protection was comparable between treatments. Nevertheless, further experimental and clinical studies are required to confirm these findings. Full article

Objectives: Renal ischemia–reperfusion (I/R) injury is one of the most important pathological triggers of acute kidney injury. This study aimed to investigate the protective effects of meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, against renal I/R injury through specific cell death pathways including inflammation, apoptosis, necroptosis, and the MAPK/ERK pathway, which is potentially linked to regulated cell death mechanisms such as ferroptosis. Methods: Male Wistar Albino rats weighing 280–300 g were used in the study and were divided into four groups: Sham, IR (40 min ischemia + 120 min reperfusion), Meloxicam + IR, and Meloxicam + IR1. Bilateral renal ischemia was induced for 40 min via a retroperitoneal approach under anesthesia. Meloxicam was administered intravenously at a dose of 1 mg/kg at the initiation of reperfusion in the Meloxicam + IR group, whereas in the Meloxicam + IR1 group, the same dose was administered 1 h after the onset of reperfusion. Total reperfusion time was 120 min in both groups. Renal function parameters (BUN and creatinine) and oxidative stress markers (TAS and TOS) were measured. Inflammatory cytokines (IL-6, IL-1β, and IL-10), the glomerular filtration injury marker Cystatin C, the tubular injury marker KIM-1, the apoptotic marker Caspase 3, the necroptosis markers RIPK3 and MLKL, and MAPK signaling pathway alterations (ERK1/2 and pERK1/2 levels) associated with cellular survival and death signaling were evaluated. Results: Most notably, meloxicam markedly modulated apoptosis, the expression of necroptosis markers RIPK3 and MLKL, and the activation of pERK1/2, a key node in MAPK signaling that is regulatory in cell survival and cell death processes. The drug also suppressed pro-inflammatory cytokines (IL-6 and IL-1β) while preserving anti-inflammatory IL-10 levels. Furthermore, improvements were observed in the levels of KIM-1, a marker of tubular injury, and Cystatin C, a marker of glomerular filtration impairment. Consequently, meloxicam administration significantly reduced the elevated serum creatinine and TOS levels observed in the IR group, although serum BUN levels remained without notable alteration. Conclusions: The findings of this study suggest that meloxicam may extend beyond its role as a classical anti-inflammatory agent, potentially offering biochemical and functional protection against renal I/R injury in association with the modulation of specific cell death mechanisms, including necroptosis and apoptosis, as well as the MAPK signaling pathway. Full article

Ovarian ischemia/reperfusion (I/R) injury is a major cause of tissue damage following the surgical detorsion of ovarian torsion and is characterized by excessive oxidative stress, inflammation, and progressive cellular injury. Although ranolazine has been reported to exert antioxidant and anti-inflammatory effects in various experimental models, its potential protective effects against ovarian I/R injury have not yet been investigated. This study aimed to evaluate whether pretreatment with ranolazine protects ovarian tissue against experimental I/R injury in rats. Twenty-four female Wistar albino rats were randomly assigned to four groups: a healthy group (HG), sham-operated group (SOG), ovarian ischemia/reperfusion (OIR) group, and ranolazine-treated ovarian ischemia/reperfusion (ROIR) group. Ovarian ischemia was induced by 1 h of torsion followed by 6 h of reperfusion. Ranolazine (50 mg/kg) was administered 1 h before the induction of ischemia as a preventive pretreatment. Oxidative stress markers (MDA, tGSH, SOD, and CAT), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), histopathological alterations, and the expression of COX-1, COX-2, IL-1β, and IL-6 were evaluated by double immunofluorescence staining. Ovarian I/R significantly increased MDA and pro-inflammatory cytokine levels while markedly decreasing tGSH levels and SOD and CAT activities (p < 0.001). These biochemical alterations were accompanied by severe follicular degeneration, mononuclear cell infiltration, interstitial edema, decreased COX-1 immunoreactivity, and increased expression of COX-2, IL-1β, and IL-6. Ranolazine treatment significantly attenuated oxidative stress and inflammatory responses, preserved the antioxidant defense system, ameliorated histopathological damage, restored COX-1 immunoreactivity, and inhibited the expression of COX-2, IL-1β, and IL-6. This is the first experimental study evaluating ranolazine in ovarian I/R injury. These findings suggest that preventive pretreatment with ranolazine attenuates experimental ovarian I/R injury through antioxidant and anti-inflammatory mechanisms. Future studies are needed to determine whether similar protective effects can be achieved when ranolazine is administered after ovarian torsion or following surgical detorsion. Full article

Background: Preservation of renal hypothermia during vascular anastomosis remains a critical yet insufficiently optimized aspect of kidney transplantation. Rewarming during the second warm ischemic period increases metabolic activity and may exacerbate ischemia–reperfusion injury. Maintaining graft temperatures below the 15–18 °C metabolic threshold during implantation is associated with improved graft preservation, yet more than 80% of grafts exceed this threshold within 20 min under standard conditions. This study evaluated the thermal performance of a novel cooling adjunct, the Ice Pillow, in limiting renal rewarming under simulated ex vivo transplant conditions. Methods: Twelve human renal allografts (six donor pairs) were studied in a controlled laboratory setting following hypothermic machine perfusion. Within each donor pair, kidneys were randomly assigned to the Ice Pillow group or the Control group. Core temperature was measured using an intra-pelvic thermocouple probe, while surface temperature was assessed with a handheld infrared thermometer. Kidneys in the Ice Pillow group were positioned on a thin gauze pouch filled with ice slush. Control kidneys were rewarmed in a simulated body cavity at 30–32 °C. Temperature recordings were obtained at one-minute intervals over 40 min. Rewarming slopes were compared using donor-paired analysis. Longitudinal temperature trajectories were analyzed using a linear mixed-effects model accounting for repeated measurements within kidneys. Agreement between core and surface measurements was evaluated using Bland–Altman analysis. Results: The Ice Pillow reduced the rate of renal rewarming by 56.4% compared with donor-paired controls (0.261 ± 0.057 °C/min vs. 0.599 ± 0.066 °C/min; mean donor-paired difference 0.338 °C/min; 95% CI, 0.237–0.440; t(5) = 8.56, p < 0.001). Linear mixed-effects modelling demonstrated progressive thermal separation between groups, with Control kidneys estimated to be 4.28 °C warmer at 10 min (95% CI, 3.35–5.22; p < 0.001) and 10.44 °C warmer at 40 min (95% CI, 7.88–12.99; p < 0.001). Bland–Altman analysis of core–surface agreement demonstrated a mean bias of −0.51 °C with 95% limits of agreement of −6.46 °C to 5.43 °C, indicating that surface thermometry followed the general direction of core temperature change but demonstrated wide limits of agreement, indicating the two methods are not interchangeable. Conclusions: In this ex vivo model, the Ice Pillow substantially attenuated renal rewarming compared with unassisted controls. Whether this thermal effect translates into improved graft function requires prospective clinical evaluation. Full article

Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a promising strategy for selected patients with refractory cardiac arrest, improving survival and the likelihood of favorable neurological outcomes. However, neurological prognostication in this setting remains highly challenging and insufficiently standardized. The pathophysiological complexity of ECPR, including global ischemia–reperfusion injury, altered cerebral perfusion, systemic inflammation, anticoagulation and prolonged sedation, limits the reliability of conventional post-cardiac arrest prognostic tools. This narrative review provides a focused and clinically oriented synthesis of current evidence on brain injury and neuroprognostication in patients undergoing veno-arterial extracorporeal membrane oxygenation (V-A ECMO) for cardiac arrest. Key determinants of neurological outcome across pre-ECMO and peri-resuscitation phases are examined, alongside the role and limitations of multimodal monitoring strategies, including neurological examination, electroencephalography, neuroimaging, cerebral oximetry and circulating biomarkers. Particular attention is given to the timing of prognostication and the risk of premature or inaccurate predictions leading to self-fulfilling prophecies. Emerging data suggest that neurological recovery in ECPR patients may be delayed, supporting a more cautious and time-adapted approach. A pragmatic, multimodal framework for neurological assessment in this population is outlined. By addressing current gaps and proposing a structured approach, this review aims to inform clinical decision making and contribute to improved neurologically meaningful survival in ECPR-treated cardiac arrest. Full article

Background: Static cold storage (SCS) remains the conventional standard for liver graft preservation; however, ischemia–reperfusion injury during storage may contribute to graft dysfunction, particularly with extended criteria and marginal donors. Machine perfusion (MP) has emerged as a promising alternative, yet existing systematic reviews are limited by their focus on individual perfusion modalities or selected donor populations. We performed a comprehensive systematic review and meta-analysis with pre-specified modality-specific subgroup analyses comparing all MP strategies with SCS in adult liver transplantation. Methods: This study was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420261355605). MEDLINE, Embase, and PubMed were systematically searched for comparative studies published between 2015 and 2025. Primary outcomes were early allograft dysfunction (EAD), primary non-function (PNF), and 1-year graft survival. Secondary outcomes included biliary complications, hepatic artery thrombosis (HAT), and postoperative transaminase levels. Pre-specified subgroup analyses were performed according to perfusion modality (NMP versus HMP/HOPE). Results: A total of 1448 records were identified. After removal of 309 duplicates and screening, 21 studies comprising 3665 patients were included. Compared with SCS, MP was associated with a significantly lower risk of EAD (RR 0.67, 95% CI 0.48–0.94; p = 0.020), PNF (RR 0.31, 95% CI 0.11–0.84; p = 0.020), and graft loss at one year (RR 0.54, 95% CI 0.36–0.81; p = 0.003; I² = 0%). Subgroup analysis demonstrated that reductions in EAD and PNF were driven by HMP/HOPE strategies (EAD: RR 0.66, 95% CI 0.45–0.98; PNF: RR 0.23, 95% CI 0.07–0.79), whereas NMP did not achieve statistical significance for these endpoints. No significant differences were observed in biliary complications or HAT. Conclusions: Machine perfusion is associated with improved early graft function, reduced primary non-function, and superior 1-year graft survival compared with static cold storage. The benefit for early graft outcomes is driven by hypothermic strategies. These findings provide modality-specific evidence to guide preservation strategy selection in clinical practice. Full article

Donation after circulatory death has emerged worldwide as a safe and effective alternative pathway to increase the donor pool. However, organs undergo a variable period of warm ischemia during the agonal phase and the cardiac arrest before graft procurement, and the heart is particularly vulnerable to injury provoked by warm ischemia and subsequent reperfusion. Several reperfusion strategies are currently available for the recovery and assessment of heart function in these donors, with promising early and long-term results. Nevertheless, each technique implies specific financial, logistical and ethical challenges, translating into a heterogeneous landscape of protocols across European and non-European countries. Additionally, no randomized clinical trials have been published to assess the superiority of one technique over the other, and current clinical evidence is based on retrospective registry data and single-center observational studies. Full article

Astrocytic function imbalance is a key factor affecting cerebral ischemia rehabilitation. Mesenchymal stem cells have therapeutic potential for cerebral ischemia, but their mechanisms remain unclear. This study explored how placental mesenchymal stem cells pro-mote astrocytes towards the A2 phenotype, which benefits the repair of cerebral ischemia injury. We established the animal model of middle cerebral artery ischemia/reperfusion and an in vitro interleukin-1β-treated astrocyte inflammation model and utilized neuro-logical function assessment, 2,3,5-triphenyltetrazolium chloride staining, immunofluorescence staining, Western blotting and other methods to evaluate the impact and associated mechanisms of transplanting placental mesenchymal stem cells into rats with cerebral ischemia–reperfusion injuries. The results demonstrated that transplantation of placental mesenchymal stem cells ameliorated neurological dysfunction and histopathological damage, alleviated neuroinflammation and enhanced neurotrophic factor levels, promoted the polarization of interleukin-1β-treated astrocytes toward the A2 phenotype, and suppressed the abundance of core mediators within the cerebral TGF β1/Smad signaling cascade in ischemia/reperfusion model. Collectively, placental mesenchymal stem cell grafting facilitates the polarization of cerebral astrocytes toward the protective A2 phenotype, presumably by regulating the TGF β1/Smad signaling cascade in ischemic brain injury. Full article

Background/Objectives: Myocardial ischemia/reperfusion (I/R) injury remains a critical challenge in cardiovascular disease management. Although Chinese yam polysaccharides (CYPs), the primary bioactive macromolecules isolated from Dioscorea opposita Thunb, exhibit well-documented antioxidant and anti-inflammatory properties, their cardioprotective efficacy against acute I/R injury and the underlying multiscale mechanisms remain unexplored. This study investigated the protective effects of CYPs using an in vivo mouse model of myocardial I/R injury. Methods: An in vivo mouse model of myocardial I/R injury was used to evaluate the effects of 7-day prophylactic CYPs treatment (400 mg/kg). Echocardiographic and histological analyses were performed, and serum myocardial injury biomarkers, oxidative stress indicators, pro-inflammatory cytokines, mitochondrial ultrastructure, ATP bioenergetics, mitochondrial respiratory chain gene expression, and gut microbiota composition were assessed. Results: Echocardiographic and histological analyses revealed that CYPs pretreatment significantly ameliorated cardiac dysfunction, as indicated by increased LVEF from 28.98% to 57.68% and reduced myocardial infarct size by 36.73% compared with the I/R group and decreased serum myocardial injury biomarkers, including CK-MB, LDH, and LDH-1. Mechanistically, CYPs exerted robust cardioprotection by mitigating oxidative damage, with MDA levels reduced by 28.83% and SOD activity increased to 1.76-fold that of the I/R group, and suppressing the release of pro-inflammatory cytokines, including Tnf-α, Il-6, and Il-1β. Crucially, CYPs intervention preserved mitochondrial ultrastructure and ATP bioenergetics, and levels increased to 1.51-fold that of the I/R group and upregulated the expression of essential mitochondrial respiratory chain genes, including mt-Nd1, mt-Nd4l, mt-Cyb, mt-CoII, and mt-Atp6. Furthermore, 16S rRNA sequencing showed that CYPs treatment reshaped gut microbiota and elevated the relative abundance of anti-inflammatory and antioxidant beneficial genus Akkermansia. Conclusions: Collectively, these findings provide novel evidence that CYPs confer profound protection against myocardial I/R injury through a multitargeted network involving the restoration of mitochondrial homeostasis, attenuation of oxidative inflammation, and modulation of the gut microbiome, highlighting CYPs as a promising functional food-derived candidate for adjunctive therapy in ischemic heart disease. Full article

Human cytomegalovirus (CMV) remains a significant infectious complication after kidney transplantation, reflecting gaps in the understanding of the molecular and immunological mechanisms regulating the transition from latency to productive infection. Following primary infection, CMV establishes lifelong latency in hematopoietic and myeloid lineage cells, maintained by viral chromatin repression and robust CMV-specific immune surveillance. CMV reactivation is associated with graft dysfunction, increased risk of rejection, opportunistic infections, and reduced patient survival. In kidney transplantation, CMV reactivation is driven by the interplay between tissue injury, inflammation, and immunosuppression. Ischemia–reperfusion injury and peri-operative stress produce reactive oxygen species, DNA damage, and pro-inflammatory cytokines (e.g., TNF-α, IL-6), which activate transcription factors such as NF-κB and AP-1. These factors regulate the CMV major immediate-early promoter (MIEP), thereby triggering lytic viral gene expression. At the same time, immunosuppressive therapies impair antiviral immune surveillance and, in some cases, induce cytokine release, potentially contributing to the pro-inflammatory environment that favors viral reactivation. In this review, we summarize current molecular and immunologic mechanisms governing CMV latency and reactivation with a focus on how immunosuppressive strategies and injury-associated pathways converge to promote CMV reactivation. We also discuss implications of risk stratification and the development of targeted therapeutic strategies to prevent CMV reactivation in kidney transplant recipients (KTRs). Full article

Inflammation plays a pivotal role in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury, highlighting inflammation suppression as a critical therapeutic strategy. The inflammatory response is largely mediated through Toll-like receptor 4 (TLR4), a transmembrane signal receptor whose expression is upregulated by Heat Shock Protein Family A Member 8 (HSPA8). Here, we investigated whether SEM1, a subunit of the 26S proteasome, interacts with HSPA8 and attenuates TLR4-mediated inflammation. Our results demonstrate that SEM1 expression is downregulated following myocardial I/R. Overexpression of SEM1 alleviated cardiac injury and dysfunction, inhibited myocardial inflammation, and downregulated HSPA8 expression in the I/R-injured heart. Co-IP assays confirmed a strong physical interaction between SEM1 and HSPA8, while the precise molecular mechanism responsible for SEM1-induced downregulation of HSPA8 remains to be fully elucidated. Mechanistically, SEM1 suppressed the activation of the TLR4/MyD88/NF-κB signaling pathway. Collectively, these findings identify SEM1 as a novel regulator that protects against myocardial I/R injury via its association with HSPA8 and inhibition of the TLR4-mediated inflammatory cascade, offering a promising therapeutic target for this condition. Full article

Coronary artery bypass grafting (CABG) remains one of the most effective treatments for advanced coronary artery disease; however, substantial variability persists in both perioperative and long-term outcomes despite advances in surgical technique, myocardial protection, and risk stratification. Oxidative stress is a central mediator of tissue injury during cardiac surgery, contributing to ischemia–reperfusion injury, endothelial dysfunction, systemic inflammation, and postoperative organ complications. At the same time, chronic exposure to ambient air pollution has emerged as an important environmental determinant of cardiovascular disease through mechanisms that converge on many of the same redox-sensitive pathways. We propose the concept of environmental oxidative priming, whereby long-term exposure to particulate matter, nitrogen oxides, ozone, and other pollutants establishes a persistent state of endothelial dysfunction, mitochondrial impairment, chronic inflammation, nitric oxide depletion, and reduced antioxidant reserve before surgery. Within this framework, CABG represents a second oxidative challenge superimposed on a pre-existing environmentally conditioned phenotype. We discuss the mechanistic overlap between air pollution-induced cardiovascular injury and cardiac surgical stress and examine how this interaction may contribute to postoperative complications, graft adaptation, major adverse cardiovascular events, and long-term survival. Recognition of air pollution as a modifier of biological resilience provides a novel framework for understanding outcome heterogeneity after CABG and may support future precision-based risk stratification and preventive strategies. Full article

Donor liver scarcity is exacerbated by preservation-related injury, particularly ischemia-reperfusion injury (IRI), which reduces organ utilization and increases discard rates. Liver sinusoidal endothelial cells (LSECs) play a critical role in mediating IRI, yet their response to static cold storage (SCS) remains poorly understood. Here, we investigate the impact of SCS on isolated rat LSECs. Isolated rat hepatocytes, stellate cells, Kupffer cells, and LSECs were subjected to up to 3 days of SCS followed by up to 2 days of recovery, with LSECs also receiving apoptosis and/or oxidative stress inhibition. Afterwards, changes in survivability, functionality, and morphology were measured. Additionally, changes in gene, cytokine, and chemokine expression were also measured. We found that SCS reduced cell viability by approximately 40%, accompanied by a 60% reduction in metabolic activity and ATP levels, indicating substantial impairment in cellular energetics. SCS also doubled reactive oxygen species (ROS) production and upregulated oxidative stress and apoptosis-related genes, leading to functional decline in LSECs. Importantly, combined inhibition of apoptosis and oxidative stress improved LSEC viability by 20% and metabolic activity and ATP levels by 30% and 40%, respectively, and reduced ROS production by 50%. These findings highlight LSEC vulnerability to preservation injury and the importance of understanding LSEC-specific injury mechanisms to provide a foundation for the development of endothelial-targeted preservation strategies to significantly improve liver transplantation outcomes, subsequently increasing access to this life-saving treatment. Full article

Background: Chronic kidney disease (CKD) is a major global health burden, affecting more than 850 million people worldwide. Increasing evidence implicates engulfment and cell motility 1 (ELMO1), a cytoplasmic adaptor protein that regulates cytoskeletal remodeling, phagocytosis, and immune responses through the ELMO1–DOCK1–Rac1 signaling axis, in renal injury and disease progression. Methods: This narrative review identified relevant publications through searches of PubMed, Web of Science, and Google Scholar using combinations of the terms “ELMO1,” “kidney disease,” “diabetic kidney disease,” “IgA nephropathy,” “focal segmental glomerulosclerosis,” “acute kidney injury,” and “renal fibrosis.” English-language original research articles, genetic association studies, mechanistic investigations, and selected review articles were preferentially included according to their relevance to ELMO1 in kidney diseases. Results: Genetic association studies have implicated the ELMO1 locus in susceptibility to diabetic kidney disease (DKD), although associated variants and effect sizes differ across populations. Experimental studies suggest that ELMO1 regulates cytoskeletal remodeling, inflammatory responses, oxidative stress, and extracellular matrix deposition through the canonical ELMO1–DOCK1–Rac1 signaling pathway as well as Rac1-independent mechanisms. Available evidence supports a role for ELMO1 in DKD and renal fibrotic remodeling. In focal segmental glomerulosclerosis, the relevance of ELMO1 is primarily inferred from Rac1-associated podocyte injury pathways, whereas evidence in acute kidney injury remains limited and context-dependent. ELMO1 may contribute to inflammatory injury in ischemia–reperfusion settings but may also support efferocytosis and tissue repair in nephrotoxic injury models. In IgA nephropathy, evidence for a direct role of ELMO1 remains limited and is currently based largely on indirect mechanistic observations involving mucosal immunity and glomerular injury responses. Conclusions: ELMO1 is a context-dependent regulator of cytoskeletal, inflammatory, oxidative, and matrix-remodeling processes relevant to kidney disease. The strongest evidence currently supports its involvement in DKD, whereas its roles in other kidney diseases remain to be further defined in disease-specific, cell-type-specific, and stage-specific experimental models. Further studies are required to clarify its potential as a biomarker or therapeutic target in CKD. Full article

Perioperative stress induces profound molecular and cellular responses that contribute to postoperative complications, including perioperative neurocognitive disorders (PND), chronic postsurgical pain, organ dysfunction, immunothrombosis, fibrosis, and cancer progression. Increasing evidence demonstrates that epigenetic mechanisms act as central regulators linking surgical trauma, inflammation, metabolic stress, ischemia–reperfusion injury, and immune activation to long-term alterations in gene expression and tissue remodeling. DNA methylation, histone modifications, chromatin remodeling, non-coding RNAs, and RNA epitranscriptomic mechanisms such as N6-methyladenosine (m6A) collectively orchestrate perioperative responses across multiple organ systems. Recent translational studies have identified histone deacetylases (HDACs), histone methyltransferases, NETosis-associated chromatin signaling, HMGB1/NF-κB activation, and epigenetic regulation of neuroimmune pathways as major contributors to postoperative cognitive dysfunction, chronic pain, cardiac dysfunction, pulmonary injury, and fibrosis. In parallel, advances in liquid biopsy, circulating tumor DNA (ctDNA), and single-cell epigenomics have opened new opportunities for biomarker-guided perioperative precision medicine. This review summarizes current evidence regarding epigenetic regulation in perioperative medicine with special emphasis on neuroepigenetics, NETosis, fibrosis, cardiac epigenetics, immune remodeling, and perioperative oncological outcomes. Furthermore, we discuss emerging therapeutic strategies targeting HDACs, DNA methylation, m6A pathways, and chromatin-associated inflammatory signaling as potential future interventions for perioperative complications. Full article