Sepsis-induced cardiac dysfunction, usually termed sepsis-induced cardiomyopathy or septic cardiomyopathy(SCM), is developed in approximately 70 % of the patients with sepsis, making it is a major concern for sepsis patients. However, the pathogenesis of SCM remain incompletely understood. Ferroptosis, a newly identified mechanism of regulated cell death, characterized by a decline in antioxidant capacity, iron accumulation, and lipid peroxidation(LPO), is involved in sepsis and SCM. Moreover, ferroptosis inhibitors confer a novel therapeutic regimen in SCM. In this Review, we first summarizes the core mechanism of ferroptosis, with an emphasis on how best to interpret ferroptosis leads to the genesis of SCM. We then highlights our focus on the emerging different types of therapeutic ferroptosis inhibitors and summarizes their pharmacological beneficial effect to treat SCM. This review highlights a novel potential therapeutic strategy for SCM by pharmacologically inhibiting ferroptosis.

Sepsis‑induced organ dysfunction syndrome (ODS) arises from a dysregulated response to infection, leading to multiple life‑threatening organ dysfunctions, and is a common complication in critically ill patients. Sepsis results in varying degrees of injury to the brain, lungs, kidneys and liver, culminating in immune dysfunction and multiple ODS (MODS). Current evidence indicates a direct correlation between the severity of organ injury and the prognosis of septic patients. Understanding the mechanisms of MODS in sepsis and developing effective management strategies are vital research areas. The protective effects of dexmedetomidine (DEX) on sepsis are well established, demonstrating its capacity to mitigate injuries to the brain, lungs, kidneys, liver and immune system. The present study reviews recent research progress on the role and mechanisms of action of DEX in the treatment of sepsis.

Mastitis is a significant concern in both human and animal medicine. The causative agent S. aureus is one of the most challenging pathogens responsible for mastitis, and the rise of its antibiotic resistance underscores the need for alternative therapies. The SESN2/Nrf2 pathway, owing to its pivotal role in regulating cellular antioxidant defenses, which are critically disrupted during ferroptosis, has recently received less attention. However, whether C3G targets the SESN2/Nrf2 pathway remains unclear, which provides a dual mechanism for treating S. aureus-induced mastitis by reducing inflammation and safeguarding mammary epithelial cells (MECs) from ferroptosis. Using a mouse mastitis and MECs model, we investigated the therapeutic potential of C3G in alleviating S. aureus-induced mastitis, focusing specifically on its role in inhibiting inflammation and modulating ferroptosis through the SESN2/Nrf2 pathway. The results demonstrated the potential antimicrobial effects of C3G against S. aureus and MRSA, suppressed inflammatory responses by downregulating pro-inflammatory markers (IL-1β, IL-6, and TNF-α), and inhibited STAT2/STAT3 signaling. Furthermore, C3G modulates ferroptosis by activating the SESN2/Nrf2 pathway, reducing oxidative stress, and protecting mammary epithelial cells from ferroptosis-induced damage. This comprehensive approach highlights C3G's potential as a novel therapeutic strategy for managing mastitis, offering an effective alternative to antibiotics in addressing both bacterial infection and inflammation.

Heat stress (HS) is a significant health concern that adversely affects both human and animal health, particularly impacting liver function due to its central metabolic role. This study investigated the mechanisms underlying HS-induced liver injury, focusing on the role of ferroptosis, an iron-dependent form of cell death characterized by lipid peroxidation and cellular iron accumulation. Using mouse and cellular HS models, the results demonstrated that HS induced liver injury through ferroptosis, as evidenced by increased levels of malondialdehyde (MDA), oxidized glutathione (GSSG), and iron, alongside decreased glutathione (GSH) and glutathione peroxidase 4 (GPX4) expression. The ferroptosis inhibitor Ferrostatin-1 (Fer-1) effectively mitigated HS-induced liver damage, reducing oxidative stress and restoring GPX4 levels. Furthermore, HS promoted the lysosomal degradation of GPX4 via the chaperone-mediated autophagy (CMA) pathway, which was regulated by heat shock cognate protein 70 (HSC70) and lysosome-associated membrane protein 2A (LAMP2A). Knockdown of LAMP2A in hepatocytes significantly suppressed HS-induced GPX4 degradation, confirming the critical role of CMA in this process. Inhibition of CMA using Apoptozole, an HSC70 inhibitor, or Bafilomycin A1 (Baf-A1), a lysosomal inhibitor, further attenuated HS-induced ferroptosis and liver injury. These findings highlight the critical role of CMA-mediated GPX4 degradation in HS-induced ferroptosis and liver injury, providing potential therapeutic targets for mitigating HS-related liver damage.

Transcatheter Aortic Valve Implantation (TAVI) is a minimally invasive procedure for treating severe aortic valve diseases but can lead to perioperative myocardial damage (PMD). Dexmedetomidine (DEX), an α2-adrenergic receptor agonist, has shown potential to reduce myocardial injury in other cardiac procedures. This effect is attributed to its anti-inflammatory properties, which help reduce the inflammatory response associated with myocardial damage, and its antioxidant properties, which combat oxidative stress that contributes to cell injury. But its effectiveness during TAVI remains unclear.

To assess the impact of DEX on myocardial injury in patients undergoing TAVI under general anesthesia.

A retrospective cohort study of 159 patients (after exclusions) who underwent TAVI from January 2022 to August 2024. Patients were divided into DEX and control groups. Primary outcomes were peak levels of cardiac troponin I and CK-MB within 48 hours postoperatively. Secondary outcomes included IL-6, PCT, and NT-proBNP levels. Propensity score matching (PSM) and Differences-in-Differences (DID) method were used for analysis.

After PSM, the DEX group exhibited significantly lower peak values of troponin I (P < 0.001) and CK-MB (P < 0.001) compared to the control group, indicating reduced myocardial injury. No significant differences were observed in IL-6, PCT, and NT-proBNP levels between the groups. The DID analysis suggested a negative correlation between DEX use and major adverse postoperative events, highlighting DEX as a potential protective factor.

Dexmedetomidine administration during TAVI was associated with reduced levels of myocardial injury markers, indicating a potential cardioprotective role. By reducing myocardial injury, DEX may contribute to improved perioperative outcomes, including a decreased risk of major adverse postoperative events. These results highlight the potential clinical utility of DEX in the perioperative management of TAVI patients, suggesting that its inclusion in anesthetic protocols could enhance patient care and recovery.

In this study, we investigated the expression levels of miR-224-3p and inflammatory factors in the lens epithelium of patients with high myopia cataract (HMC) to determine how miR-224-3p/ACSL4 affects ferroptosis and inflammation in human lens epithelial cells (HLECs). The capsule tissues (including lens epithelial cells) of 36 patients with HMC and 36 patients with age-related cataract (ARC) were taken respectively. 18HMC and 18ARC capsule tissues were selected for RNA sequencing (RNA-Seq) and the rest were used for qPCR assays. The expression of miR-224-3p and ACSL4 in the capsules of patients was detected by qPCR, and RNA was extracted from each of the six capsules. To evaluate ferroptosis and inflammation, the levels of expression of ACSL4, GPX4, TFR1 and IL-6 was determined by immunohistochemistry, Transmission electron microscopy image showed the structure of mitochondria. The differential expression of mir-224-3p was identified through RNA sequencing, with its expression significantly increased in HMC. As a result, mir-224-3p was chosen for further experimentation. The expression levels of ACSL4, TFR1 and GPX4 varied between HMC and ARC. Target Scan predicted a direct binding site between mir-224-3p and ACSL4. The results showed that the expression levels of miR-224-3p, TFR1 and IL-6 in the HMC patients were significantly greater than those in ARC. ACSL4 and GPX4 in HMC were considerably lower than those in ARC. Electron microscopy images revealed that the mitochondria of HMC were significantly shrunken compared to those of ARC. So it was thought that ferroptosis and inflammation occured in HMC patients. A dual-luciferase report found miR-224-3p regulated ACSL4. PCR and WB assays revealed that ACSL4 was the downstream target gene of miR-224-3p. We also found that miR-224-3p promoted the proliferation and migration of HLECs. TNF-α (20 ng/mL) induced an inflammatory response in HLECs. Also, miR-224-3p effectively inhibited ferroptosis in HLECs induced by erastin, meanwhile the expression levels of Fe2+, MDA, ROS, and TFR1 were reduced, while GPX4 and GSH expression levels were elevated. The level of expression of IL-6 was decreased. Additionally, miR-224-3p increased the viability of HLECs by regulating ferroptosis and inflammation via ACSL4 targeting.

Sepsis is a life‑threatening organ dysfunction disorder caused by dysfunctional host response to infection. Sepsis‑induced cardiomyopathy (SIC) is a common and serious complication of sepsis, and it is associated with increased mortality rates; however, its specific pathogenesis is still unclear. Ferroptosis, which is an iron‑dependent form of programmed cell death, is involved in the pathophysiology of SIC. Further study on the mechanism and therapeutic targets of ferroptosis in SIC may provide new strategies for clinical diagnosis and treatment of this condition. The present article reviews the mechanisms between SIC and ferroptosis, summarizes the progress in research of the involvement of ferroptosis in SIC and provides new potential strategies for further research and treatment in the future.

Post-stroke depression (PSD) poses a serious impact on patients' life quality. Effective drugs to treat this annoying disease are still being sought. Yi-nao-jie-yu (YNJY) prescription has been found to relieve PSD; however, the underlying mechanisms remain unelucidated. This work elucidated the therapeutic effects and mechanisms underlying YNJY prescription in PSD. PSD rat model was treated with YNJY prescription and ML385. Depression-like behaviors of rats was appraised. Hematoxylin-eosin, Nissl, and NeuN immunofluorescence staining were performed to observe hippocampal neuronal damage. Transmission electron microscopy was used to assess hippocampal mitochondrial damage. Commercial kits and western blotting were adopted to research ferroptosis-related factors and Nrf2/GPX4/SLC7A11 signals. In vitro experiments were performed using rat hippocampal neurons to explore the mechanism by which YNJY prescription relieves PSD. In PSD rats, YNJY prescription relieved depression-like behaviors, attenuated hippocampal neuronal damage, mitigated hippocampal ferroptosis and mitochondrial damage, and activated hippocampal Nrf2/GPX4/SLC7A11 pathway. By in vitro experiments, erastin treatment exacerbated hippocampal neuronal damage, ferroptosis, mitochondrial damage, and lipid peroxidation; however, YNJY prescription abolished these erastin-induced effects. In the erastin-treated hippocampal neuronal model of PSD, ML385 treatment increased ferroptosis, hippocampal neuronal damage, and lipid peroxidation; however, YNJY prescription counteracted these ML385-induced effects. By in vivo study, ML385 reversed the relief of YNJY prescription on depressive-like behaviors of PSD rats, and the inhibition on ferroptosis in PSD rats' hippocampus. YNJY prescription relieves PSD by blocking ferroptosis via activating the Nrf2/GPX4/SLC7A11 pathway. It may be a promising agent for treating PSD clinically.

Sepsis is a major cause of mortality, particularly in patients with myocardial injury. The objective of this study was to evaluate the impact of dexmedetomidine, propofol, and midazolam on mortality and various outcomes in this population.

A retrospective cohort study was performed using the eICU database, encompassing 2,171 septic patients with myocardial injury. Patients were categorized into single- and multiple-sedative groups. The primary endpoint was 100-day mortality, with secondary endpoints encompassing hospital stay, intensive care unit (ICU) stay, mechanical ventilation (MV), and dialysis. Statistical analysis was conducted using Cox regression, Kaplan-Meier curves, and propensity score matching.

Among 2,171 patients, dexmedetomidine was associated with lower 100-day mortality in patients with APACHE IV scores < 78.9, particularly in specific subgroups. In patients with APACHE IV scores ≥ 78.9, dexmedetomidine provided no mortality advantage over propofol. Midazolam was linked to higher mortality across all score ranges, and its combination with propofol resulted in worse outcomes compared to dexmedetomidine-propofol. No significant differences were found in hospital stay, ICU stay, or MV rates between the groups.

Dexmedetomidine improves prognosis in septic patients with myocardial injury, particularly in those with lower severity of illness, highlighting its potential as a preferred sedative choice in this population.

To investigate the effect of ultrasound-guided bilateral superficial cervical plexus nerve blocks with Ropivacaine or a combination of different adjuvants on perioperative analgesia and quality of postoperative recovery in patients undergoing radical thyroid cancer surgery under general anesthesia with nerve monitoring without muscarinic maintenance.

A total of 140 patients undergoing elective radical thyroid cancer surgery were randomly divided into four groups, with 35 cases in each group: general anesthesia alone group (Group C), general anesthesia + Ropivacaine group (Group R), general anesthesia + Ropivacaine combined with dexmedetomidine group (Group R1), and general anesthesia + Ropivacaine combined with dexamethasone group (Group R2). The primary observation index were postoperative resting and active Visual Analogue Score. The secondary observation index were hemodynamics, intraoperative sedative and analgesic medication use, postoperative analgesic requirements, postoperative recovery indicators, Richards-Campbell Sleep Questionnaire scores, Quality of Postoperative Recovery-15 scores, and adverse reactions.

Compared with group C, the resting and active VAS scores in group R were lower within 12 h after surgery (P < 0.05), the resting and active VAS scores in groups R1 and R2 were lower within 24 h after surgery (P < 0.05). Compared with group R, the VAS scores of patients in groups R1 and R2 were lower within 6 to 24 h after operation (P < 0.05). Compared with group R2, only the sedation score after extubation was higher in R1 group (P < 0.05), and there was no statistical difference in any other aspects (P < 0.05).

Bilateral superficial cervical plexus nerve blocks with Ropivacaine or a combination of different adjuvants are superior to general anesthesia alone in terms of intraoperative hemodynamics, the amount of sedative and analgesic drugs, and analgesic efficacy and quality of recovery in patients undergoing radical thyroid cancer surgery with nerve monitoring without muscarinic maintenance. Ropivacaine combined with an adjuvant has better analgesic effectiveness and quality of recovery than without an adjuvant, and Ropivacaine combined with dexmedetomidine has a better sedation level than dexamethasone.

The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and the activities of digestive organs. Additionally, muscle tissues serve an endocrine function by secreting myogenic cytokines, thereby regulating metabolism throughout the entire body. Maintaining muscle function requires iron homeostasis. Recent studies suggest that disruptions in iron metabolism and ferroptosis, a form of iron-dependent cell death, are essential contributors to the progression of a wide range of muscle diseases and disorders, including sarcopenia, cardiomyopathy, and amyotrophic lateral sclerosis. Thus, a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention. This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury, as well as associated muscle diseases and disorders. Moreover, we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders. Finally, we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.

The available data on the effect of dexmedetomidine premedication on anesthesia depth in children during general anesthesia are limited. This study was designed to determine the effect of preoperative dexmedetomidine administration on the bispectral index (BIS) and sevoflurane requirements in children during sevoflurane anesthesia.

120 children aged 5 to 12 years undergoing concealed penis repair or hypospadias plastic surgery were randomized to receive preoperative administration of 0.25 µg kg- 1 dexmedetomidine, 0.5 µg kg- 1 dexmedetomidine, 0.75 µg kg- 1 dexmedetomidine, or the same volume of placebo. The primary outcome was the change in the BIS value from before dexmedetomidine administration to 60 min after surgical incision. The secondary outcomes included the end-tidal sevoflurane concentration (ETsevo), hemodynamic data, anesthesia recovery data and intraoperative awareness.

Compared with those in Group C, the BIS values of children in Group D2 and Group D3 were significantly lower during sevoflurane induction and early maintenance (P < 0.017). Moreover, children in Group D2 and Group D3 had a lower ETsevo (P < 0.001) during sevoflurane maintenance than did those in Group C (P < 0.017). There were statistically significant differences in heart rate(P < 0.0001) and mean arterial pressure(P < 0.001) between the groups, but the incidence of bradycardia or hypotension was similar between the groups (p = 0.779 and p = 0.901).

Children who received 0.5 µg kg- 1 or 0.75 µg kg- 1 dexmedetomidine preoperatively were more likely to achieve the target depth of anesthesia (BIS less than 60) during anesthesia induction and had lower BIS values during the early stage of anesthesia maintenance.

The trial is registered with the China Clinical Trials Registry Registration Number: ChiCTR1900026872. Date of registration: 10/24/2019.

Sepsis is a life-threatening form of organ dysfunction resulting from a dysregulated response to infection. The complex pathogenesis of sepsis poses challenges because of the lack of reliable biomarkers for early identification and effective treatments. As sepsis progresses to severe forms, cardiac dysfunction becomes a major concern, often manifesting as ventricular dilation, a reduced ejection fraction, and a diminished contractile capacity, known as sepsis-induced cardiomyopathy (SIC). The absence of standardized diagnostic and treatment protocols for SIC leads to varied criteria being used across medical institutions and studies, resulting in significant outcome disparities. Despite the high prevalence of SIC, accurate statistical data are lacking. To understand how SIC affects sepsis prognosis, a thorough exploration of its pathophysiological mechanisms, including systemic factors and complex signalling within myocardial and immune cells, is required. Identifying the factors influencing SIC occurrence and progression is crucial and must be conducted within specific clinical contexts. In this review, the clinical manifestations, pathophysiological mechanisms, and treatment strategies for SIC are discussed, along with the clinical background. We aim to connect current practices with future research challenges, providing clear guidance for clinicians and researchers.

Sepsis rapidly contributed to multiorgan failure, most typically damaging the cardiovascular system, and there were no effective treatments. Dexmedetomidine (Dex) has good therapeutic effects on sepsis-induced organ injury. Our work aimed to probe the pharmacological effects of Dex on ferroptosis in sepsis-associated myocardial injury (S-MI) and define underlying mechanism of action. Cardiomyocytes were exposed to lipopolysaccharide (LPS) for mimicking S-MI model in vitro. The septic mice were constructed by cecum ligation and puncture operation. The mRNA and protein expressions were assessed using quantitative real-time polymerase chain reaction or western blot. Cell survival was determined by cell counting kit-8, lactic dehydrogenase release, and flow cytometry assays. 2',7'-Dichlorodihydrofluorescein diacetate staining measured cellular reactive oxygen species level. The secretion levels of inflammatory cytokines, ferroptosis-related indicators were analyzed by enzyme-linked immunosorbent assay. The N6-methyladenosine (m6A) modification level of protein arginine methyltransferase 5 (PRMT5) mRNA was examined by methylated RNA binding protein immunoprecipitation (Me-RIP) assay. The interaction between methyltransferase like 3 (METTL3)/fat mass and obesity-associated protein (FTO) and PRMT5 was analyzed by RNA immunoprecipitation assay. Dex treatment alleviated LPS-induced cardiomyocyte injury and ferroptosis, while these effects of Dex were reversed by Erastin treatment. Mechanically, Dex ameliorated PRMT5 expression in LPS-induced cardiomyocytes by regulating METTL3/FTO catalyzed m6A modification on PRMT5 mRNA. Rescue experiments confirmed that PRMT5 overexpression abolished Dex-mediated inhibitory roles on LPS-induced cardiomyocyte injury and ferroptosis. Moreover, Dex administration alleviated inflammation, ferroptosis, and myocardial injury in septic mice. Taken together, Dex repressed PMRT5 expression in a m6A-dependent manner, thus lightening LPS-triggered ferroptosis to alleviate cardiomyocyte injury.

This study aimed to investigate the potential protective effects of Dexmedetomidine (DEX) against acute kidney injury (AKI) induced by acute stress (AS). Wistar rats were divided into five groups: Control, DEX, AS, AS + DEX, and AS + A438079. The results showed that AS led to AKI by increasing inflammatory biomarkers and oxidative stress-related indicators. The acute stress model in rats was successfully established. Renal function, histopathology, oxidative stress, and inflammation were assessed. Localization of P2X7 receptor (P2X7R) was determined by immunofluorescence. Additionally, the key inflammatory proteins of the P2X7R/NF-κB/NLRP3 signaling pathway were measured by Western blotting. DEX significantly improved kidney function, alleviated kidney injury, and reduced oxidative stress and inflammation. DEX inhibited the activation of the P2X7R, decreased the expression of NF-κB, NLRP3 inflammasome, and Caspase-1, and inhibited the expression of interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα). Furthermore, DEX also alleviated AS-induced AKI by inhibiting the excessive production of reactive oxygen species (ROS) and reducing oxidative stress. In conclusion, DEX attenuates AS-induced AKI by mitigating inflammation and oxidative stress through the inhibition of the P2X7R/NF-κB/NLRP3 pathway in rats.

Previous studies demonstrated that dexmedetomidine (Dex) posttreatment aggravated myocardial dysfunction and reduced survival in septic mice. Yet, whether Dex elicits similar effects in septic patients as defined by Sepsis-3 remains unknown. This study sought to assess the effects of Dex-based sedation on mortality and cardiac dysfunction in septic patients defined by Sepsis-3 and to further reveal the mechanisms in septic rats. In the retrospective cohort study, patients were categorised into sepsis with Dex, other sedatives (propofol or midazolam) or without sedatives, mortality at 28 days were compared, and patients with measurements of cardiovascular biomarkers and echocardiography were used to examine the effect of Dex on cardiac dysfunction. Septic rats and Langendorff-perfused isolated rat hearts were used, cardiac function, mortality and pro-inflammatory mediators were analyzed. The all-cause mortality of septic patients receiving Dex reached to 35.2 % on Day 28, significantly higher than that of patients with other sedatives (16.1 %), while no difference with group of no sedatives (27.3 %). Patients in Dex group showed lower left ventricular EF and lateral mitral annular early diastolic peak velocities, but higher interventricular septum diastolic dimension compared to those with other sedatives. The plasma levels of H-FABP, NT-proBNP and HMGB1 in Dex and other sedative groups showed no difference, while both were significantly lower than the group of no sedative. Notably, Dex posttreatment deteriorated cardiac dysfunction, increasing mortality in septic rats with enhanced systemic and myocardial proinflammatory mediators, including TNF-α, IL-1β, IL-6 and VCAM-1. Mechanistical study by Langendorff-perfusion revealed that Dex directly acted on the heart, aggravating LPS-induced myocardial inflammation and dysfunction. These results suggest that Dex increases mortality and deteriorates myocardial dysfunction compared with other sedatives in septic patients defined by Sepsis 3.0, maybe partly through promoting proinflammatory response via directly acting on the heart.

Sepsis is a life-threatening condition resulting from pathogen infection and characterized by organ dysfunction. Programmed cell death (PCD) during sepsis has been associated with the development of multiple organ dysfunction syndrome (MODS), impacting various physiological systems including respiratory, cardiovascular, renal, neurological, hematological, hepatic, and intestinal systems. It is well-established that pathogen infections lead to immune dysregulation, which subsequently contributes to MODS in sepsis. However, recent evidence suggests that sepsis-related opportunistic pathogens can directly induce organ failure by promoting PCD in parenchymal cells of each affected organ. This study provides an overview of PCD in damaged organ and the induction of PCD in host parenchymal cells by opportunistic pathogens, proposing innovative strategies for preventing organ failure in sepsis.

Abdominal aortic aneurysm (AAA) is a cardiovascular disease with potentially fatal consequences, yet effective therapies to prevent its progression remain unavailable. Oxidative stress is associated with AAA development. Carbon dots have reactive oxygen species-scavenging activity, while green tea extract exhibits robust antioxidant properties. However, the potential of green tea derived carbon dots in mitigating AAA progression has not been fully elucidated. In this study, tea polyphenol carbon dots (TP-CDs) were synthesized via hydrothermal methods and characterized for their antioxidant properties. The antioxidant effects of TP-CDs were evaluated, and TP-CDs' impact on phenotypic transformation, oxidative stress, apoptosis and ferroptosis was investigated comprehensively in an Ang II-induced AAA model, employing techniques such as Western blotting, flow cytometry, and immunohistochemistry. The results revealed that TP-CDs effectively alleviated oxidative stress induced by Ang II stimulation, thereby inhibiting phenotypic transformation, apoptosis, and ferroptosis in vivo. Furthermore, treatment with TP-CDs significantly attenuated AAA progression in a mouse AAA model. Overall, these findings demonstrate that TP-CDs reduced reactive oxygen species levels in the microenvironment and alleviated the progression of AAA, offering a promising therapeutic strategy for this condition.

Myocardial ischemia/reperfusion injury (MIRI) is closely associated with ferroptosis. Dexmedetomidine (Dex) has good therapeutic effects on MIRI. This study investigates whether dexmedetomidine (Dex) regulates ferroptosis during MIRI by affecting ferroportin1 (FPN) levels and elucidates the underlying mechanisms.

A murine MIRI model was established using male C57BL/6 J mice subjected to 30 min of left anterior descending coronary artery ligation followed by 48 h of reperfusion. In vitro, cardiomyocyte hypoxia/reoxygenation (H/R) models were created with 16 h of hypoxia and 8 h of reoxygenation. Triphenyltetrazolium chloride (TTC) staining was employed to determine infarct size. The pathological changes in myocardial tissues were assessed using hematoxylin-eosin (HE) staining. Lipid reactive oxygen species (ROS) level was detected using BODIPY™ 581/591 C11, and ferrous iron (Fe2+) and malondialdehyde (MDA) levels were measured using the kits. Cardiomyocyte viability was examined using cell counting kit-8 (CCK8) assay. The histone H3 lysine 27 acetylation (H3K27Ac) level in the FPN promoter region was determined using DNA pulldown assay. Chromatin immunoprecipitation (ChIP) assay was used to investigate the relationship between histone deacetylase 2 (HDAC2) and FPN promoter.

Dex alleviated ferroptosis in cardiomyocytes by upregulating FPN levels, which mitigated H/R-induced oxidative damage. FPN knockdown abolished the protective effects of Dex, confirming its dependence on FPN expression. Additionally, HDAC2 knockdown alleviated I/R-induced myocardial injury and ferroptosis in mice. Moreover, H/R-induced HDAC2 upregulation transcriptionally inhibited FPN expression by reducing the H3K27Ac level in the FPN promoter region, but Dex therapy restored this impact via inhibition of HDAC2. As expected, HDAC2 overexpression partially reversed the inhibitory effect of Dex on H/R-mediated cardiomyocyte ferroptosis.

Dex alleviated H/R-mediated cardiomyocyte ferroptosis through regulating the HDAC2/FPN axis. Our findings lend theoretical support to the use of Dex in MIRI therapy.

Tianxiangdan (TXD), a traditional Chinese herbal remedy, demonstrates efficacy in mitigating myocardial ischemia-reperfusion (I/R)-induced damage. This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R. High-performance liquid chromatography-mass spectrometry (HPLC-MS) identified 86 compounds in TXD. Network pharmacological analysis predicted potential target genes and their modes of action. Cardiac function, ischaemic ST changes, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, myocardial fiber, and infarct size were assessed using in vivo and in vitro I/R injury models. Estrogen receptor alpha (ERα) protein expression and estradiol (E2) levels were measured to confirm TXD's impact on estrogen levels and ERα expression. To examine if TXD reduces I/R injury through ERα, an AZD group (300 nmol·L-1 AZD9496 and 15% TXD serum) was compared to a TXD group (15% TXD serum). The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway. I/R injury-induced ferroptosis was identified using a Fer-1 group (1.0 μmol·L-1 Fer-1 and 15% TXD serum) to elucidate the potential association between ferroptosis and ERα proteins. A DCFH-DA probe detected reactive oxygen species (ROS) and Fe2+, while Western blotting assessed target protein expression. Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels, improving cardiac injury biomarkers (LDH, MDA, and SOD), alleviating pathological features, and preventing I/R-induced loss of cell viability in vitro. The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells. The TXD group showed significantly decreased ROS and Fe2+ levels, while the AZ group (treated with AZD9496) exhibited increased levels. The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4 (GPX4), with reduced levels of P53 protein and ferritin-heavy polypeptide 1 (FTH1). The AZ group exhibited contrasting effects on these expression levels. The literature indicated a novel connection between ERα and ferroptosis. TXD activates the ERα signaling pathway, promoting protection against I/R-induced myocardial cell ferroptosis. This study provides evidence supporting TXD use for myocardial ischemia treatment, particularly in older female patients who may benefit from its therapeutic outcomes.

The pathophysiology of cardiovascular disease (CVD) is complex and presents a serious threat to human health. Cardiomyocyte loss serves a pivotal role in both the onset and progression of CVD. Among various forms of programmed cell death, ferroptosis, along with apoptosis, autophagy and pyroptosis, is closely linked to the advancement of CVD. Ferroptosis, a mechanism of cell death, is driven by the buildup of oxidized lipids and excess iron. This pathway is modulated by lipid, amino acid and iron metabolism. Key characteristics of ferroptosis include disrupted iron homeostasis, increased peroxidation of polyunsaturated fatty acids due to reactive oxygen species, decreased glutathione levels and inactivation of glutathione peroxidase 4. Treatments targeting ferroptosis could potentially prevent or alleviate CVD by inhibiting the ferroptosis pathway. Ferroptosis is integral to the pathogenesis of several types of CVD and inhibiting its occurrence in cardiomyocytes could be a promising therapeutic strategy for the future treatment of CVD. The present review provided an in‑depth analysis of advancements in understanding the mechanisms underlying ferroptosis. The present manuscript summarized the interplay between ferroptosis and CVDs, highlighting its dual roles in these conditions. Additionally, potential therapeutic targets within the ferroptosis pathway were discussed, alongside the current limitations and future directions of these novel treatment strategies. The present review may offer novel insights into preventive and therapeutic approaches for CVDs.

Kidney transplantation is a pivotal treatment for end-stage renal disease. However, renal ischemia-reperfusion injury (IRI) during surgery significantly impacts graft function. Despite unclear molecular mechanisms, no specific therapies or preventative measures are available. Gene expression profiles from renal biopsies before and after IRI were downloaded from public databases. Differentially expressed genes were identified using the Wilcoxon rank-sum test and weighted gene co-expression network analysis. Ferroptosis-associated genes were screened using the FerrDb database. The genes with the highest connectivity were identified via the protein-protein interaction (PPI) network and upstream regulatory miRNAs were found through the gene-miRNA network. A mouse renal IRI model was constructed for transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) validation to elucidate the relationship between key ferroptosis genes and regulatory miRNAs in renal IRI. Differential analysis identified 15 ferroptosis-associated genes (TNFAIP3, IL6, KLF2, EGR1, JUN, ZFP36, GDF15, CDKN1A, HSPB1, BRD2, PDK4, DUSP1, SLC2A3, DDIT3, and CXCL2) involved in renal IRI regulation. In animal experiments, ferroptosis-related genes were also upregulated in the model group. Enrichment analysis and hematoxylin-eosin pathological staining suggested these genes are primarily involved in renal inflammatory responses. PPI network analysis revealed IL6 as the gene with the highest connectivity, and the gene-miRNA network indicated IL6 might be regulated by miR-let-7a. Animal experiments revealed decreased miR-let-7a and increased IL6 levels in the model group, identifying potential therapeutic targets. MiR-let-7a regulates ferroptosis in renal IRI by targeting IL6, highlighting IL6 as a crucial gene in the ferroptosis process of renal IRI.

Cerebral ischemia/reperfusion injury (IRI) is pathologically associated with ferroptosis. Dexmedetomidine (Dex) exerts neuroprotective activity after cerebral IRI. Our work focused on probing the pharmacologic effect of Dex on ferroptosis during cerebral IRI and the mechanisms involved. Cerebral IRI models were established by oxygen-glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion (MCAO). 2,3,5-Triphenyltetrazolium chloride (TTC) staining was utilized to detect cerebral infarct size and mNSS was performed to evaluate neurologic deficits. Brain pathologic changes were analyzed by HE staining. Lipid peroxidation level was detected by C11-BODIPY staining, and Fe2+ and MDA levels were measured using the kits. Cell vitality was examined by CCK-8 assay. Dual-luciferase reporter and ChIP assays were adopted to determine the interaction between SOX9 and DMT1 promoter. Dex ameliorated ferroptosis and neuronal death induced by MCAO and OGD/R. SOX9 upregulation abolished the inhibitory effect of Dex on OGD/R-induced ferroptosis and neuronal death in SH-SY5Y cells. Our further trials showed that SOX9 transcriptionally activated DMT1 expression. As expected, DMT1 overexpression prevented Dex-induced decrease in ferroptosis and neuronal death in OGD/R-treated SH-SY5Y cells. Dex inhibited ferroptosis to exert neuroprotection effects on cerebral IRI by inactivating the SOX9/DMT1 axis.

Sepsis is a complicated clinical disease caused by a defective host response to infection, leading to elevated morbidity and fatality globally. Sepsis patients have a significant risk of life-threatening organ damage, including hearts, brains, lungs, kidneys, and livers. Nevertheless, the molecular pathways driving organ injury in sepsis are not well known. Ferroptosis, a non-apoptotic cell death, occurs due to iron metabolism disturbance and lipid peroxide buildup. Multiple studies indicate that ferroptosis has a significant role in decreasing inflammation and lipid peroxidation during sepsis. Ferroptosis inhibitors and medications, aimed at the most studied ferroptosis process, including Xc-system, Nrf2/GPX4 axis, and NCOA4-FTH1-mediated ferritinophagy, alleviating sepsis effectively. However, few clinical trials demonstrated ferroptosis-targeted drugs's effectiveness in sepsis. Our study examines ferroptosis-targeted medicinal agents and their potential benefits for treating sepsis-associated organ impairment. This review indicates that ferroptosis suppression by pharmaceutical means may be a useful therapy for sepsis-associated organ injury.

Ischemia-reperfusion injuries (IRI) across various organs and tissues, along with sepsis, significantly contribute to the progression of critical illnesses. These conditions disrupt the balance of inflammatory mediators and signaling pathways, resulting in impaired physiological functions in human tissues and organs. Ferroptosis, a distinct form of programmed cell death, plays a pivotal role in regulating tissue damage and modulating inflammatory responses, thereby influencing the onset and progression of severe illnesses. Recent studies highlight that pharmacological agents targeting ferroptosis-related proteins can effectively mitigate oxidative stress caused by IRI in multiple organs, alleviating associated symptoms. This manuscript delves into the mechanisms and signaling pathways underlying ferroptosis, its role in critical illnesses, and its therapeutic potential in mitigating disease progression. We aim to offer a novel perspective for advancing clinical treatments for critical illnesses.

Sepsis-induced cardiomyopathy is a common complication of sepsis and is associated with higher mortality. To date, effective diagnostic and management strategies are still lacking. Recent studies suggest that ferroptosis plays a critical role in sepsis-induced cardiomyopathy and ferroptosis inhibitor Ferrostatin-1 (Fer-1) improved cardiac dysfunction and survival in lipopolysaccharide (LPS) induced endotoxemia. However, the effects of Fer-1 in cardiac dysfunction in the early stages of cecal ligation and puncture (CLP) induced sepsis remains unclear. Our study aims to elucidate the role of Fer-1 in the acute phase of peritonitis sepsis induced cardiac injury.

CLP was used to induce peritonitis sepsis in mice. Pretreatment of ferroptosis inhibitor ferrostatin-1 (Fer-1) was used in the in vivo models. Survival was monitored for 48h. Cardiac function and histology were analyzed 6h after surgery. We found that ejection fraction (EF) remained normal at 6h after CLP, but the contractility detected by cardiac muscle strain analysis was significantly reduced, along with increased immune cell infiltration. Pretreating the CLP mice with 5 mg/kg Fer-1 significantly reduced mortality. At 6h after CLP, ferroptosis key regulator Gpx4, cardiac iron and malonaldehyde (MDA) did not change, but ferroptosis marker gene expression increased. Fer-1 treatment showed beneficial effects in cardiac function, less myocardial inflammatory cytokine expression and significantly inhibited immune cells, especially neutrophil infiltration in the heart. Consistently, expression of neutrophil associated chemokines (Ccrl2, Cxcl2, Cxcl3 and Cxcl5) as well as extracellular matrix (ECM) degradation enzymes (Adamts1, Adamts4, Adamts9 and Mmp8) significantly decreased in Fer-1 pre-treated CLP heart.

Our findings suggest that Fer-1 inhibits neutrophil infiltration in early sepsis by disrupting the chemokine axis, highlighting its potential as a therapeutic option to manage acute immune overactivation in early stages of sepsis-induced cardiomyopathy.

The lungs are highly susceptible to damage during sepsis, with severe lung injury potentially progressing to acute respiratory distress syndrome and even fatal sepsis. Effective efferocytosis of apoptotic cells is crucial in alleviating inflammation and tissue injury.

We established a septic lung injury mouse model via intraperitoneal injection of lipopolysaccharide. Lung injury was assessed by histology, immunofluorescence, neutrophil immunohistochemistry staining, and cytokine detection. We extracted alveolar macrophages by bronchoalveolar lavage and primary macrophages from mouse bone marrow to investigate the regulatory effects of Dexmedetomidine (DEX) on efferocytosis. We further validated the molecular mechanisms underlying the regulation of macrophage efferocytosis by DEX through knockdown of AXL expression. Additionally, we examined the efferocytic ability of monocytes isolated from patients.

We discovered that DEX treatment effectively alleviated pulmonary injury and inflammation. Lipopolysaccharide reduced macrophage efferocytosis and AXL expression which were reversed by DEX. We also found DEX inhibited the increased activation of A Disintegrin And Metalloproteinase 10 (ADAM10) and the production of soluble AXL. Moreover, our findings demonstrated that DEX decreased the elevated ROS production linked to higher ADAM10 activation. Blocking AXL negated DEX's benefits on efferocytosis and lung protection. Efferocytosis in monocytes from septic lung injury patients was notably lower than in healthy individuals.

Our findings demonstrated that DEX treatment effectively reduces septic lung injury by promoting macrophage efferocytosis through ROS/ADAM10/AXL signaling pathwway.

Acute lung injury (ALI) significantly impacts the survival rates in intensive care units (ICU). Releasing a lot of pro-inflammatory mediators during the progression of the disease is a core feature of ALI, which may lead to uncontrolled inflammation and further damages the tissues and organs of patients. This study explores the potential therapeutic mechanisms of Dexmedetomidine (Dex) in ALI.

In present study, cecal ligation puncture (CLP)-established ALI model mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cell line were established to discover the influence of Dex. The evaluation of lung injury in vivo using histopathology, TUNEL assay, and analysis of inflammatory factors in bronchoalveolar lavage fluid (BALF) and serum. The receptor for advanced glycation end products (RAGE)/Caspase-11-dependent pyroptosis-related proteins and macrophage polarization markers were analyzed using western blot, immunofluorescence, and flow cytometry. Finally, the mechanism of Dex in macrophages was further verified in vitro.

In vivo, Dex alleviated lung injury and decreased TUNEL-positive cell expression in CLP group. Dex decreased tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and IL-17A levels in BALF and serum, while increasing IL-10 expression. Dex treatment decreased the protein levels of RAGE, caspase-11, IL-1β and Gasdermin-D (GSDMD) in both in cells and in mice. Dex also down-regulated the synthesis of inducible nitric oxide synthase (iNOS) of classical activation phenotype (M1) markers, and up-regulated the synthesis of CD206 and Arg-1 of alternate activation phenotype (M2) markers.

Dex treatment can inhibit inflammation and reduce lung injury caused by CLP. It could be associated with mediating M1 and M2 polarization and suppressing RAGE/Caspase-11-depended pyroptosis.

Sepsis is a critical condition characterized by a systemic inflammatory response to infection, often leading to severe vascular dysfunction and high mortality. One of the hallmarks of vascular dysfunction in sepsis is increased vascular permeability and the loss of pericytes, which are essential for maintaining vascular integrity. Despite the significance of pericyte loss in sepsis, the primary type of cell death responsible and the underlying molecular mechanisms remain incompletely understood. This study aims to elucidate these mechanisms by focusing on ferroptosis, a form of programmed cell death, and its regulation through the Hippo/ACSL4 axis. Our research confirmed significant pericyte loss in patients with sepsis. Through advanced single-cell analysis and proteomics, ferroptosis was identified as a key differentiating cell death type between sepsis and sham samples. Further metabolomics analysis revealed that Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) plays a pivotal role in the ferroptosis of pericytes during sepsis. In vitro experiments demonstrated that downregulation of ACSL4 effectively reduced lipopolysaccharide (LPS)-induced lipid peroxidation, restored pericyte viability, and improved endothelial permeability. In vivo studies with pericyte-specific ACSL4 knockout mice showed a marked decrease in pericyte loss and enhanced vascular barrier function following sepsis induction. To translate these findings into potential therapeutic strategies, we developed pericyte-targeting liposomes encapsulating ACSL4 shRNA adenovirus. These liposomes successfully restored pulmonary vascular barrier function and significantly reduced pericyte loss in septic conditions. The results of this study underscore the crucial role of ACSL4 in mediating ferroptosis in pericytes and highlight the therapeutic potential of targeting ACSL4 to mitigate vascular dysfunction in sepsis.

Cardiovascular disease remains the leading cause of death worldwide. Dexmedetomidine is a highly selective α2 adrenergic receptor agonist with sedative, analgesic, anxiolytic, and sympatholytic properties, and several studies have shown its possible protective effects in cardiac injury. The aim of this review is to further elucidate the underlying cardioprotective mechanisms of dexmedetomidine, thus suggesting its potential in the clinical management of cardiac injury.

Our review summarizes the findings related to the involvement of dexmedetomidine in cardiac injury and discusses the results in the light of different mechanisms. We found that numerous mechanisms may contribute to the cardioprotective effects of dexmedetomidine, including the regulation of programmed cell death, autophagy and fibrosis, alleviation of inflammatory response, endothelial dysfunction and microcirculatory derangements, improvement of mitochondrial dysregulation, hemodynamics, and arrhythmias. Dexmedetomidine may play a promising and beneficial role in the treatment of cardiovascular disease.

Sepsis results in high mortality and is associated with organ dysfunction caused by infection. The present study aimed to elucidate whether early-stage sympathetic activation is associated with the prognosis of sepsis and its possible mechanisms.

Patients with sepsis and healthy controls were included. Sepsis in rats was induced by lipopolysaccharide. Dexmedetomidine, a α2-adrenergic receptor agonist, was used in patients and rats with sepsis to evaluate the role of the sympathetic nervous system in sepsis. Holter monitoring was used to detect heart rate variability, while plasma samples were obtained to measure levels of norepinephrine and inflammatory markers. Mean arterial pressure, heart rate, and renal sympathetic nerve activity were recorded. Immunofluorescence was used to detect the activation of neurons in the rostral ventrolateral medulla (RVLM).

In patients with sepsis, plasma levels of norepinephrine and interleukin-1β were higher compared with those in controls and positively correlated with acute physiology and chronic health evaluation (APACHE) II. SDNN and SDANN were significantly reduced as well as negatively correlated with APACHE II. Meanwhile, rats with sepsis showed increased of sympathetic outflow and plasma levels of norepinephrine, with increased c-fos levels in the RVLM. Treatment with dexmedetomidine could improve prognosis. Lesion of tyrosine hydroxylase-positive neurons in the RVLM attenuated sympathetic activation and target organs damage in septic rats as well as improved survival.

The results suggest that tyrosine hydroxylase-positive neurons in the RVLM might contribute to the prognosis of sepsis via activation of the sympathetic nervous system, while dexmedetomidine could ameliorate sepsis via inhibiting sympathetic activation.

This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats.

CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 μg/kg, and CP + Dex 25 μg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting.

Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1.

Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.

Ferroptosis is a newly recognized type of regulated cell death that is characterized by the accumulation of iron and lipid peroxides in cells. Studies have shown that ferroptosis plays a significant role in the pathogenesis of various diseases, including cardiovascular diseases. In cardiovascular disease, ferroptosis is associated with ischemia-reperfusion injury, myocardial infarction, heart failure, and atherosclerosis. The molecular mechanisms underlying ferroptosis include the iron-dependent accumulation of lipid peroxidation products, glutathione depletion, and dysregulation of lipid metabolism, among others. This review aims to summarize the current knowledge of the molecular mechanisms of ferroptosis in cardiovascular disease and discuss the potential therapeutic strategies targeting ferroptosis as a treatment for cardiovascular disease.

Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), is a silent killer that often progresses to metabolic dysfunction-associated steatohepatitis (MASH). To date, there are no pharmacological treatments for MASLD. While obesity is a major cause of the development and progression of MASLD, the underlying mechanisms remain unclear. We hypothesize that ferroptosis, a recently discovered nonapoptotic iron-dependent form of cell death, is activated during the progression of MASLD and may be a potential target for treating MASLD. Using a murine model of Western diet-induced obesity, C57BL/6J male mice were exposed to a long-term (36 weeks) Western diet. Controls were maintained with a standard chow diet. Western diet-induced obesity was confirmed by increased body mass index (BMI). Histopathological analysis demonstrated the progression of MASLD to MASH in the obese group, which was accompanied by significant hepatic iron deposition, oxidative damage, and lipid peroxidation. Hepatic ferroptosis was further confirmed by decreased protein expression of glutathione peroxidase 4 (GPX4) and increased acyl-CoA synthetase long-chain family member 4 (ACSL4), markers of ferroptosis. These findings suggest that ferroptosis is a potential mechanism involved in the pathogenesis of MASLD in male mice.

This study aimed to investigate whether Cr(VI) can induce ferroptosis in chicken hepatocytes and determine the role of PERK-mediated endoplasmic reticulum stress (ERS). First, a model of Cr(VI) poisoning was established by exposing chicken hepatocytes to Cr(VI). The levels of ferroptosis-related proteins, meanwhile, GSH, SOD, MDA, and lipid ROS, were measured. Furthermore, the expression of GRP78 and PERK proteins was examined. Changes in ERS and ferroptosis were evaluated by silencing the PERK gene. Results showed that Cr(VI) led to the accumulation of lipid ROS, decreased expression of GPX4 and HSP27, increased expression of COX2, and induced ferroptosis in chicken hepatocytes. Exposure to Cr(VI) increased the protein expression of GRP78 and PERK, and silencing of PERK worsened Cr(VI)-induced ferroptosis. In conclusion, Cr(VI) can induce ferroptosis in chicken hepatocytes, and PERK plays an important role as a negative regulator.

Cell death constitutes a critical component of the pathophysiology of cardiovascular diseases. A growing array of non-apoptotic forms of regulated cell death (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified and is intimately linked to various cardiovascular conditions. These forms of RCD are governed by genetically programmed mechanisms within the cell, with epigenetic modifications being a common and crucial regulatory method. Such modifications include DNA methylation, RNA methylation, histone methylation, histone acetylation, and non-coding RNAs. This review recaps the roles of DNA methylation, RNA methylation, histone modifications, and non-coding RNAs in cardiovascular diseases, as well as the mechanisms by which epigenetic modifications regulate key proteins involved in cell death. Furthermore, we systematically catalog the existing epigenetic pharmacological agents targeting novel forms of RCD and their mechanisms of action in cardiovascular diseases. This article aims to underscore the pivotal role of epigenetic modifications in precisely regulating specific pathways of novel RCD in cardiovascular diseases, thus offering potential new therapeutic avenues that may prove more effective and safer than traditional treatments.

Dexmedetomidine (DEX) has been confirmed to exert neuroprotective effects in various nerve injury models by regulating ferroptosis, including spinal cord injury (SCI). Although it has been established that CDGSH iron sulfur domain 2 (CISD2) can regulate ferroptosis, whether DEX can regulate ferroptosis by CISD2 in SCI remains unclear. Lidocaine was used to induce PC12 cells and stimulate rats to establish SCI models in vitro and in vivo. MTT assays were performed to analyze cell viability. Ferroptosis was assessed by determining the levels of cellular reactive axygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and Fe2+. Ferritinophagy was analyzed by LysoTracker staining, FerroOrange staining, and immunofluorescence. Western blotting was carried out to quantify the levels of several proteins. Fluorescence microscopy was also used to observe cell autophagy. The morphology of mitochondria within the tissue was observed under transmission electron microscopy (TEM). DEX treatment weakened lidocaine-induced elevation of ROS, Fe2+, and MDA and reduced GSH in PC12 cells, indicating that DEX treatment weakened lidocaine-induced ferroptosis in PC12 cells. Similarly, lidocaine promoted autophagy, Fe2+, and microtubule-associated protein 1 light chain 3 (LC3) in PC12 cells and suppressed ferritin and p62 protein levels, indicating that DEX could weaken lidocaine-induced ferritinophagy in PC12 cells. DEX treatment improved the BBB score, reduced tissue damage, increased the number of neurons, and alleviated mitochondrial damage by inhibiting ferroptosis and ferritinophagy in lidocaine-induced SCI rat models. The decreased CISD2, ferritin heavy chain 1 (FTH1), solute carrier family 7-member 11-glutathione (SLC7A11), and glutathione peroxidase 4 (GPX4) protein levels and the elevated nuclear receptor coactivator 4 (NCOA4) protein levels in rat models in the lidocaine group were weakened by DEX treatment. Moreover, CISD2 inhibition reversed the inhibitory effects of DEX treatment on lidocaine-induced ferroptosis and ferritinophagy in PC12 cells significantly. Taken together, DEX treatment could impair lidocaine-induced SCI by inhibiting ferroptosis and ferritinophagy by upregulating CISD2 in rat models.

Vital organ injury is one of the leading causes of global mortality and socio-economic burdens. Current treatments have limited efficacy, and new strategies are needed. Dexmedetomidine (DEX) is a highly selective α2-adrenergic receptor that protects multiple organs by reducing inflammation and preventing cell death. However, its exact mechanism is not yet fully understood. Understanding the underlying molecular mechanisms of its protective effects is crucial as it could provide a basis for designing highly targeted and more effective drugs. Ferroptosis is the primary mode of cell death during organ injury, and recent studies have shown that DEX can protect vital organs from this process. This review provides a detailed analysis of preclinical in vitro and in vivo studies and gains a better understanding of how DEX protects against vital organ injuries by inhibiting ferroptosis. Our findings suggest that DEX can potentially protect vital organs mainly by regulating iron metabolism and the antioxidant defense system. This is the first review that summarizes all evidence of ferroptosis's role in DEX's protective effects against vital organ injuries. Our work aims to provide new insights into organ therapy with DEX and accelerate its translation from the laboratory to clinical settings.

Radical resection of colon cancer under general anesthesia is one of the main treatment methods for this malignancy. However, due to the physiological characteristics of elderly patients, the safety of perioperative anesthesia needs special attention. As an α2-adrenergic receptor agonist, dexmedetomidine (Dex) has attracted much attention from anesthesiologists due to its stabilizing effect on heart rate and blood pressure, inhibitory effect on inflammation, and sedative and analgesic effects. Its application in general anesthesia may have a positive impact on the quality of anesthesia and postoperative recovery in elderly patients undergoing radical resection of colon cancer.

To investigate the anesthetic effects of Dex during radical surgery for colon cancer under general anesthesia in elderly patients.

A total of 165 colon cancer patients who underwent radical surgery for colon cancer under general anesthesia at Qingdao University Affiliated Haici Hospital, Qingdao, China were recruited and divided into two groups: A and B. In group A, Dex was administered 30 min before surgery, while group B received an equivalent amount of normal saline. The hemodynamic changes, pulmonary compliance, airway pressure, inflammatory factors, confusion assessment method scores, Ramsay Sedation-Agitation Scale scores, and cellular immune function indicators were compared between the two groups.

Group A showed less intraoperative hemodynamic fluctuations, better pulmonary compliance, and lower airway resistance compared with group B. Twelve hours after the surgery, the serum levels of TLR-2, TLR-4, IL-6, and TNF-α in group A were significantly lower than those of group B (P < 0.05). After extubation, the Ramsay Sedation-Agitation Scale score of group A patients was significantly higher than that of group B patients, indicating a higher level of sedation. The incidence of delirium was significantly lower in group A than in group B (P < 0.05).

The use of Dex as an adjunct to general anesthesia for radical surgery in elderly patients with colon cancer results in better effectiveness of anesthesia.