Xiaoyun Fu

Sepsis-induced cardiomyopathy (SICM) is a common and severe complication of sepsis that contributes substantially to circulatory instability, organ dysfunction, and adverse clinical outcomes. Mitochondrial dysfunction and metabolic reprogramming have emerged as central mechanisms underlying its pathogenesis. Because the adult myocardium depends heavily on mitochondrial lipid metabolism for continuous energy production, disruption of lipid metabolic homeostasis may critically impair myocardial bioenergetics and stress adaptation during sepsis. Current evidence indicates that SICM is accompanied by extensive abnormalities in mitochondrial lipid metabolism, including impaired fatty acid uptake and oxidation, pathological cardiolipin remodeling, excessive lipid peroxidation, ferroptosis, disrupted lipid droplet–mitochondria interactions, and defective mitochondrial dynamics and quality control. These alterations interact with inflammatory signaling, redox imbalance, and metabolism-associated post-translational modifications, collectively promoting adenosine triphosphate (ATP) depletion, lipotoxicity, oxidative injury, and cardiac dysfunction. This review summarizes the physiological organization of mitochondrial lipid metabolism in the healthy myocardium and systematically examines the mechanisms responsible for its dysregulation in SICM. Particular emphasis is placed on cardiolipin remodeling and mitochondrial membrane lipid homeostasis as potential links among impaired substrate oxidation, respiratory chain instability, oxidative stress amplification, and myocardial injury. Emerging therapeutic strategies aimed at restoring metabolic flexibility, preserving mitochondrial membrane integrity, limiting lipid peroxidation, and improving mitochondrial quality control are also evaluated. A better understanding of these mechanisms may support earlier recognition of metabolically distinct SICM phenotypes, improve the timing and selection of targeted interventions, and facilitate the development of more precise approaches to reducing sepsis-related cardiac injury and improving patient outcomes.

Chronic obstructive pulmonary disease (COPD) is a common reason for admission to the intensive care unit (ICU), where accurate risk stratification is cruci

The mammalian colon lumen exists in a highly anaerobic environment (oxygen partial pressure (PO ₂ ) < 1 mmHg), which promotes the growth of beneficial obligate anaerobes (OA) while limiting the expansion of pathogenic facultative anaerobes (FA). Gut dysbiosis is associated with a wide range of human diseases, and is often characterized by an overgrowth of FA, particularly those in the Enterobacteriaceae family. Oxygen (O ₂ ) plays a crucial role in bacterial physiology and ecology, and increased O ₂ availability is a key driver of gut dysbiosis. O ₂ therapy is commonly used for hypoxic patients, either through inhalation or extracorporeal membrane oxygenation (ECMO), both of which can expose the gut to excess O ₂ , known as hyperoxia. Hyperoxia leads to the overproduction of reactive O ₂ species, resulting in organ injury and worsening clinical outcomes. Viewing gut dysbiosis from an ecological perspective highlights the disruption of host mechanisms that regulate the gut microbiota, particularly in the context of antibiotic use and a western (low fiber) diet, where physiological hypoxia in the colonic epithelium is compromised. This review extends that perspective to O ₂ therapy in acute care, discussing the rationale and experimental evidence linking hyperoxia to gut dysbiosis, with a focus on venoarterial (VA)-ECMO support as a potential contributor. Understanding these mechanisms could help clinicians optimize O ₂ management during therapy.

Sepsis-induced cardiomyopathy (SICM), a critical contributor to the high mortality rate associated with sepsis, involves complex pathophysiological mechanisms that remain incompletely elucidated. In recent years, dysregulation of bidirectional signaling communication between mitochondria and the nucleus has been recognized as a pivotal factor in the pathogenesis of SICM. The anterograde signaling pathways—including the PGC-1α/NRF1/NRF2 axis, SIRT3-mediated deacetylation, and TFAM-dependent mitochondrial DNA (mtDNA) maintenance—are suppressed by inflammation and metabolic disturbances. This suppression leads to impaired mitochondrial biogenesis and disrupted energy metabolism. Concurrently, within retrograde signaling pathways, molecular mediators such as reactive oxygen species (ROS), mtDNA, and calcium signaling activate pro-inflammatory and apoptotic pathways, notably NF-κB and cGAS-STING. This activation establishes a vicious cycle perpetuating inflammation and cellular damage. Although current targeted interventions aimed at modulating mitochondrial-nuclear crosstalk have demonstrated some efficacy in animal models, their clinical translation faces significant challenges. These include the dynamic nature of the disease, substantial interindividual variability, and difficulties in achieving targeted delivery. This review summarizes the mechanisms of mitochondrial-nuclear bidirectional signaling in SICM and explores potential therapeutic targets, aiming to provide novel insights for SICM treatment strategies. Graphical Abstract

Aims: Sepsis-induced cardiomyopathy (SIC) is a serious complication of sepsis. The relationship between SIC and protein acetylation, particularly the balance between acetylation and deacetylation in cardiomyocyte subcellular structures, as well as how nuclear–mitochondrial coordination maintains standard antioxidant stress capacity, remains unclear. This study focused on exploring the nuclear–mitochondrial regulatory mechanisms formed by the interplay of Sirtuin 3 (SIRT3) and Forkhead box O3a (FOXO3a). Results: In vivo , SIC markers increased significantly in wild-type CLP (Cecal Ligation and Puncture) mice at 72 h (CLP72h) but were partially reversed in CLP72h+oeSIRT3 mice. CLP72h mice exhibited significantly reduced mitochondrial area, aspect ratio, and mtDNA copy number. Echocardiography revealed significantly impaired cardiac function. Western blotting showed significantly decreased nuclear and mitochondrial long-form SIRT3, nuclear long-form and mitochondrial short-form FOXO3a, and mitochondrial superoxide dismutase 2 (SOD2), with significantly increased acetylation in CLP72h mice. In vitro , oeSIRT3 preserved nuclear FOXO3a localization and mitochondrial membrane potential, with CLP72h+oeSIRT3 mice showing significantly reduced oxidative stress. The long form of SIRT3 plays a crucial deacetylation role in SIC and influences SOD2 partially through FOXO3a. Innovation: This study explored the roles of different SIRT3 and FOXO3a isoforms in combating oxidative stress in SIC through dynamic nucleus-mitochondrial regulation. Conclusion: This study underscores the critical role of the SIRT3-FOXO3a axis in enhancing mitochondrial antioxidant capacity through a nuclear–mitochondrial network during SIC, offering new insights into molecular mechanisms and potential therapeutic strategies for SIC. Antioxid. Redox Signal. 43, 805–818.

Rationale: The important etiological treatment for hyperlipidemic severe acute pancreatitis is to reduce blood lipid. Statins or fibrates are often selected in clinical practice. Most reports indicate that statins or statin combination therapy can cause serious complications such as rhabdomyolysis syndrome (RM) and even poor prognosis. However, in fact, RM may also occur when fibrates alone are used to reduce blood lipid. Patient concerns: A 25-year-old man was admitted to our hospital for a 2-day history of abdominal pain, nausea, and vomiting. This patient presented with typical clinical manifestations of acute pancreatitis such as abdominal pain, abdominal distension, nausea, vomiting, and difficulty in defecation after a greasy diet. Auxiliary examinations such as blood (urine) amylase, lipase, blood lipid, abdominal computed tomography, and color Doppler ultrasound confirmed hyperlipidemic severe acute pancreatitis. However, after admission, during the treatment for reducing blood lipid, the blood creatine kinase index of the patient continued to increase, reaching more than 200 times the upper limit of normal at the highest. Accompanied by typical clinical manifestations, rhabdomyolysis was considered. After discussions among experts in the department, differentiations were mainly made from drugs after admission, recent history of toxicant exposure, history of trauma, past history of similar rhabdomyolysis, and other etiologies causing elevated myocardial enzyme spectrum. Finally, it was considered related to bezafibrate. Diagnoses: RM. Interventions: Bezafibrate tablets for lowering blood lipids were immediately discontinued. On the second day after discontinuation, there was a small decrease in creatine kinase. Then, appropriate fluid infusion, alkalinization of urine, addition of plasma exchange, and bedside continuous renal replacement therapy were administered. Outcomes: The level of muscle enzymes decreased progressively and finally returned to normal before discharge. Lessons: In clinical practice, it is necessary to dynamically monitor the changes of liver and kidney functions and myocardial enzyme spectrum when using bezafibrate tablets to treat hyperlipidemic pancreatitis.

Digestive diseases represent a diverse and complex group of systemic disorders, often marked by intricate pathogenic mechanisms and substantial rates of morbidity, disability, and mortality. While effective therapies exist for certain conditions, such as peptic ulcers, gastrointestinal hemorrhage, and viral hepatitis, many others remain difficult to manage due to their limited treatment options, poor response to current therapies, and multifactorial etiologies. As a result, there is a pressing need to develop novel therapeutic agents that offer greater specificity and improved clinical outcomes. Edaravone, a free radical scavenger widely used in the management of neurological disorders, has demonstrated a favorable safety profile and minimal adverse effects. Recent research has expanded our understanding of Edaravone’s pharmacological actions, revealing its broad therapeutic potential beyond the nervous system. Its capacity to neutralize reactive oxygen species, reduce oxidative stress, suppress inflammation, inhibit apoptosis, modulate immune function, and enhance tissue repair positions it as a promising candidate for treating digestive disorders. This review highlights current advances in the application of Edaravone in digestive disease models and clinical settings, to offer new perspectives for future prevention, therapeutic strategies, and scientific investigation in this field.