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BACKGROUND: The repair process of myocardial injury involves complex cellular and molecular mechanisms, especially mitochondrial calcium homeostasis, macrophage autophagy and pyroptosis pathways. Traditional Chinese medicine (TCM) has shown significant clinical efficacy in improving myocardial injury, but its mechanism of action needs to be thoroughly investigated. OBJECTIVE: To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury, and to summarize the progress of TCM in this field. METHODS: A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science, PubMed and CNKI. The search terms were “mitochondrial calcium homeostasis, macrophage autophagy, macrophage pyroptosis, traditional Chinese medicine, myocardial injury, myocardial injury reperfusion” in Chinese and English. Through literature review, we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis, explored the mechanism of their roles in myocardial injury, and summarized the pathways of multi-targeted, multipathway effects of TCM. RESULTS AND CONCLUSION: The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes. Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways. Autophagy contributes to cell clearance and regulation of inflammatory response, while pyroptosis affects myocardial repair by releasing inflammatory factors. TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms. For example, astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C, and epimedium glycoside plays a role in reducing β-amyloid deposition. In addition, herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways, such as PI3K/AKT and nuclear factor-κB signaling pathways. Future studies should focus on the interactions between mitochondrial calcium homeostasis, autophagy and pyroptosis pathways, as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury. [ABSTRACT FROM AUTHOR]

BACKGROUND: Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects, but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury. Therefore, it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE: To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS: CNKI, WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024. The search terms used were “flap, ischemia-reperfusion injury, inflammatory response, oxidative stress, Ca2+ overload, apoptosis, mesenchymal stem cells, platelet-rich plasma, signaling pathways, shock wave, pretreatment” in Chinese and English. After elimination of irrelevant literature, poor quality and obsolete literature, 77 documents were finally included for review. RESULTS AND CONCLUSION: Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response, oxidative stress response, Ca2+ overload, and apoptosis, which can cause apoptosis of vascular endothelial cells, vascular damage and microcirculation disorders in the flap, and eventually lead to flap necrosis. Studies have found that mesenchymal stem cell transplantation, platelet-rich plasma, signaling pathway modulators, shock waves, and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees, and reduce the necrosis rate and necrosis area of the grafted flap. Although there are many therapeutic methods for skin flap ischemia/reperfusion injury, a unified and effective therapeutic method has not yet been developed in the clinic, and the advantages and disadvantages of various therapeutic methods have not yet been compared. Most of the studies remain in the stage of animal experiments, rarely involving clinical observations. Therefore, a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic. [ABSTRACT FROM AUTHOR]

To investigate the protective role of high dose melatonin concerning myocardial I/R injury and inflammation in patients undergoing on-pump coronary artery bypass grafting (CABG) surgery by evaluating IR/inflammatory biomarkers and clinical outcomes. This was a prospective; randomized; single-blinded placebo-controlled study conducted at cardio-thoracic surgery department of the Academy of the Cardiovascular and Thoracic Surgery, Ain Shams University. Eligible patients were randomly allocated to; melatonin-treated group (MTG) or placebo-treated group (PTG). The MTG (n = 17) received 60 mg/day melatonin capsules daily starting 5 days before surgery in addition to the standard of care. PTG (n = 17) received placebo also 5 days before surgery plus standard of care. The levels of nuclear factor kappa beta (NF-κb) (primary outcome), tumor necrosis factor (TNF-α), cardiac troponins I, and IL-6 levels were all assessed for both groups at five time points: baseline before melatonin or placebo administration (T0), before cross-clamp application(T1), 5 min after cross-clamp removal(T2), 6 h after cross-clamp removal(T3) and 24 h after cross-clamp removal(T4). Blood pressure was assessed at baseline, pre-operative and 24-hours post-operative. The Quality of recovery-40 score (QOR-40) was assessed for both groups on day 4 after surgery. TNF-α levels decreased in the MTG at T1(p = 0.034) versus PTG. At T2(p = 0.005), and T3(p = 0.04), TNF-α significantly increased in PTG versus MTG. Troponins significantly increased in PTG at T3 (p = 0.04) versus MTG. NF-κB levels declined at T1 (p = 0.013) and T2 (p = 0.0001) in MTG compared to PTG. IL-6 significantly increased in PTG versus MTG at T3 (p = 0.04). The QOR-40 score significantly decreased in MTG versus PTG. MTG had statistically significant decrease in DBP compared to the placebo group (p = 0.024). MTG had a statistically significant shorter intubation time than did the placebo group (p = 0.03). Melatonin 60 mg was well-tolerated without any reported side effects. Our findings suggested that melatonin could ameliorate myocardial I/R injury after on-pump CABG and that this outcome was essentially correlated to its antiapoptotic and anti-inflammatory effects. Trial registration: ClinicalTrials.gov registration number NCT05552586, 9/2022. [ABSTRACT FROM AUTHOR]

Interleukin-34 (IL-34) was recently reported to be a new biomarker for atherosclerosis diseases, such as coronary artery disease and vascular dementia. IL-34 regulates the expression of proinflammatory cytokines (IL-17A, IL-1 and IL-6), which are classical cytokines involved in myocardial ischemia‒reperfusion (MI/R) injury. However, the exact role of IL-34 in MI/R remains unknown. In this study, a rat MI/R model was used to explore the effect of IL-34 on modulating inflammatory processes during MI/R injury. First, eighteen rats were subjected to 30 min of LAD ligation followed by 0 h, 1 h, 2 h, 4 h, 8 h or 24 h of reperfusion (n = 3 for each group). The level of IL-34 peaked at 4 h after MI/R in the ischemic myocardium. Next, ischemia for 30min and reperfusion for 4h (I/R) model was used. 24 rats were randomly divided into I/R group (n = 8), IL-34+IR group (n = 8) and IL-34+ab12+IR group (n = 8). We found that IL-34 pretreatment increased the expression of inflammatory cytokines, including high mobility group Box 1 (HMGB1), IL-17A, and IL-6; the expression of the apoptosis protein cleaved caspase-3; and the Bcl-2/Bax ratio within the ischemic myocardium. We also observed increased serum cardiac enzymes and a larger myocardial injury area. Treatment with a Janus kinase (JAK) pathway inhibitor, however, partially reduced the expression of these proteins and attenuated myocardial injury. Together, these results showed that IL-34 aggravates MI/R injury by inducing the expression of the HMGB1-IL-17A-IL-6 axis and apoptosis after MI/R, which is partially dependent on the JAK pathway. Therefore, blocking the JAK signaling pathway or inhibiting IL-34 expression might provide a new idea to reduce MI/R injury, but further researches are needed. [ABSTRACT FROM AUTHOR]

The graphic was created with BioRender.com. [Display omitted] Hepatic ischemia–reperfusion injury (HIRI) is an important cause of liver injury following liver transplantation and major resections, and neutrophils are the key effector cells in HIRI. Double-negative T regulatory cells (DNT) are increasingly recognized as having critical regulatory functions in the immune system. Whether DNT expresses distinct immunoregulatory mechanisms to modulate neutrophils, as in HIRI, remains largely unknown. In this study, we found that murine and human DNT highly expressed CD39 that protected DNT from extracellular ATP-induced apoptosis and generated adenosine in tandem with CD73, to induce high levels of neutrophil apoptosis. Furthermore, extracellular adenosine enhanced DNT survival and suppressive function by upregulating survivin and NKG2D expression via the A2AR/pAKT/FOXO1 signaling pathway. Adoptive transfer of DNT ameliorated HIRI in mice through the inhibition of neutrophils in a CD39-dependent manner. Lastly, the adoptive transfer of A2ar -/- DNT validated the importance of adenosine/A2AR signaling, in promoting DNT survival and immunomodulatory function to protect against HIRI in vivo. In conclusion, purinergic signaling is crucial for DNT homeostasis in HIRI. Augmentation of CD39 or activation of A2AR signaling in DNT may provide novel therapeutic strategies to target innate immune disorders. [ABSTRACT FROM AUTHOR]

The correction notice in the journal "Frontiers in Pharmacology" addresses errors in Figures 3, 4, 5, 7, and 8 of the article "Ginkgolide C alleviates myocardial ischemia/reperfusion-induced inflammatory injury via inhibition of CD40-NF-κB pathway." The corrected figures show the effects of ginkgolide C on infarct size, ultrastructure of myocardial tissue, histopathological changes, and expressions of ICAM-1, VCAM-1, iNOS, CD40, NF-κB, and other proteins in a rat model of myocardial ischemia/reperfusion injury. The authors emphasize that the views expressed in the article are their own and do not necessarily reflect those of their institutions or the publisher. [Extracted from the article]

Increasing evidence shows that inflammation plays a vital role in the occurrence and development of ischemia/reperfusion (I/R). Suppression of excessive inflammation can ameliorate impaired cardiac function, which shows therapeutic potential for clinical treatment of myocardial ischemia/reperfusion (MI/R) diseases. In this study, we investigated whether Ginkgolide C (GC), a potent anti-inflammatory flavone, extenuated MI/R injury through inhibition of inflammation. In vivo , rats with the occlusion of the left anterior descending (LAD) coronary artery were applied to mimic MI/R injury. In vitro , primary cultured neonatal ventricular myocytes exposed to hypoxia/reoxygenation (H/R) were applied to further discuss the anti-H/R injury property of GC. The results revealed that GC significantly improved the symptoms of MI/R injury, as evidenced by reducing infarct size, preventing myofibrillar degeneration and reversing the mitochondria dysfunction. Moreover, histological analysis and Myeloperoxidase (MPO) activity measurement showed that GC remarkably suppressed Polymorphonuclears (PMNs) infiltration and ameliorated the histopathological damage. Furthermore, GC pretreatment was shown to improve H/R-induced ventricular myocytes viability and enhance tolerance of inflammatory insult, as evidenced by suppressing expression of CD40, translocation of NF-κB p65 subunit, phosphorylation of IκB-α, as well as the activity of IKK-β. In addition, downstream inflammatory cytokines modulated by NF-κB signaling were effectively down-regulated both in vivo and in vitro , as determined by immunohistochemistry and ELISA. In conclusion, these results indicate that GC possesses a beneficial effect against MI/R injury via inflammation inhibition that may involve suppression of CD40-NF-κB signal pathway and downstream inflammatory cytokines expression, which may offer an alternative medication for MI/R diseases. [ABSTRACT FROM AUTHOR]

Purpose: Due to its increased volume, polycystic ovarian tissue is more prone to torsion than normal ovarian tissue. In treating ovarian torsion, detorsion is applied to ensure oxygenation of hypoxic tissues. However, the resulting oxygen radicals cause tissue damage. Bromelain is a substance obtained from pineapple, and studies in the literature show it is used as an antioxidant. This study aimed to evaluate the damage caused by ischemia-reperfusion (I/R) in the torsion-detorsion model created in normal and polycystic ovarian tissue and investigate the role of bromelain in this damage. Methods: Polycystic ovarian tissue was created by applying dihydroepiandrosterone sulfate to rats. Afterward, a torsion-detorsion model was used for all rats. The rats were divided into six groups: the polycystic ovary sham-operated group (P-S), the normal ovary sham-operated group (N-S), the polycystic ovary ischemia/reperfusion group (P-IR), the normal ovary ischemia/reperfusion group (N-IR), the polycystic ovary ischemia/reperfusion group treated with bromelain (P-IRB), and the normal ovary ischemia/reperfusion group treated with bromelain (N-IRB). After the procedure, tissues were collected for histopathological examination, and MDA, TUNEL, and NF-κB levels were measured. Results: This study detected significant decreases in MDA and NF-κB levels and apoptotic cell numbers assessed by TUNEL staining in groups with IR damage and given bromelain compared to the control groups. The number of TUNEL-positive cells was found to be highest in the P-IR group (8.80 ± 2.98) and significantly lower in the bromelain-administered P-IRB (1.04 ± 1.09) and N-IRB (0.52 ± 0.58) groups (p< 0.05). NF-κB expression was also high in P-IR and N-IR groups, while it was significantly decreased in bromelain-treated groups (P-IRB and N-IRB) (p< 0.05). In addition, IR damage was more pronounced in polycystic ovary tissue than in normal ovary tissue. Conclusion: Ischemia perfusion damage may be more pronounced in polycystic ovarian tissue than in normal ovarian tissue. Bromelain may be preferred to prevent I/R injury caused by ovarian torsion. It is also thought that bromelain may function in treating polycystic ovaries, and further studies can be conducted on this subject. [ABSTRACT FROM AUTHOR]

As an important element of the human body, iron participates in numerous physiological and biochemical reactions. In the past decade, ferroptosis (a form of iron-dependent regulated cell death) has been reported to contribute to the pathogenesis and progression of various diseases. The stability of iron in cardiomyocytes is crucial for the maintenance of normal physiological cardiac activity. Ferroptosis has been detected in many cardiovascular diseases (CVDs), including coronary heart disease, myocardial ischemia–reperfusion injury, heart failure, and chemotherapy-induced myocardial damage. In cardiomyocytes, epigenetic regulation and post-translational modifications regulate the expression of ferroptosis-related factors, maintain iron homeostasis, and participate in the progression of CVDs. Currently, there is no detailed mechanism to explain the relationship between epigenetic regulation and ferroptosis in CVDs. In this review, we provide an initial summary of the core mechanisms of ferroptosis in cardiomyocytes, with first focus on the epigenetic regulation and expression of ferroptosis-related factors in the context of common cardiovascular diseases. We anticipate that the new insights into the pathogenesis of CVDs provided here will inspire the development of clinical interventions to specifically target the active sites of these factors, reducing the harmfulness of ferroptosis to human health. [ABSTRACT FROM AUTHOR]

The study aimed to elucidate the underlying pharmacological mechanism of the traditional Chinese medicine Pue in ameliorating myocardial ischemia-reperfusion injury (MIRI), a critical clinical challenge exacerbated by reperfusion therapy. In vivo MIRI and in vitro anoxia/reoxygenation (A/R) models were constructed. The results demonstrated that Pue pretreatment effectively alleviated MIRI, as manifested by diminishing the levels of serum CK-MB and LDH, mitigating the extent of myocardial infarction and enhancing cardiac functionality. Additionally, Pue significantly alleviated histopathological damage in MIRI-treated myocardium, as evidenced by HE staining and TUNEL assay. In vitro, Pue pretreatment significantly alleviated A/R-induced damage by decreasing LDH levels, increasing cellular activity, inhibiting autophagic lysosomal overactivation, inhibiting oxidative stress (ROS, LIP ROS, MDA), increasing antioxidant defense (SOD, GSH-Px), and increasing P62 protein expression while decreasing LC3II/I ratio. Furthermore, Pue inhibited apoptosis and maintained mitochondrial homeostasis by up-regulating the expression of Hairy and Enhancer of Split-1 (HES1) protein, which was crucial for its cardioprotective effects. Nevertheless, the cardioprotective efficacy of Pue pretreatment was negated via the knockdown of HES1 protein expression via pAD/HES1-shRNA transfection. In conclusion, Pue effectively ameliorated HES1-mediated MIRI-induced autophagy, apoptosis, and mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

The document provides abstracts from the 28th Congress of the Spanish Society for Surgery Research in 2024, covering a wide range of topics such as implantable devices for drug delivery, flow dynamics simulation, soft skills training in residency, nerve regeneration, and vascular graft studies. Research includes investigations into treatments for myocardial infarction, vascular graft development, and the therapeutic use of menstrual blood-derived stromal cells for heart attack management. Other studies focus on predicting small intestine length for bariatric surgery, predictive algorithms for bariatric surgery, advanced therapies for post-myocardial infarction ventricular dysfunction, and surgical skills training in fetoscopy and fetal surgery. The document also delves into laparoscopic ureteral obstruction modeling, artificial intelligence in robotic surgery education, vascular graft validation, endovascular procedures for stroke in large animals, and bioinformatic analyses on the therapeutic potential of secretomes from menstrual blood-derived stromal cells. [Extracted from the article]

Objective(s): Ischemia/reperfusion (IR)-induced ventricular arrhythmia, which mainly occurs after the opening of coronary artery occlusion, poses a clinical problem. This study aims to investigate the effectiveness of pretreatment with coenzyme Q10 (CoQ10) in combination with mitochondrial transplantation on IR-induced ventricular arrhythmias in aged rats. Materials and Methods: Myocardial IR induction was performed by left anterior descending coronary artery occlusion for 30 min, followed by re-opening for 24 hr. CoQ10 was administered intraperitoneally at a dosage of 10 mg/kg/day for two weeks before inducing IR. At the start of reperfusion, 500 µl of the respiration buffer containing 6x106±5x105 mitochondria/ml of respiration buffer harvested from the pectorals major muscle of young donor rats were injected intramyocardially. To investigate arrhythmias, the heart's electrical activity during ischemia and the first 30 min of reperfusion were recorded by electrocardiogram. After 24 hr of reperfusion, cardiac histopathological changes, creatine kinase-MB, nitric oxide metabolites (NOx), oxidative stress markers (malondialdehyde, total antioxidant, superoxide dismutase, and glutathione peroxidase), and the expression of genes regulating mitochondrial fission/fusion were measured. Results: Pretreatment with CoQ10 in combination with mitochondrial transplantation reduced ventricular arrhythmias, cardiac histopathological changes, and creatine kinase-MB levels. Simultaneously, this combined therapeutic approach increased myocardial NOx levels, fostering an improved oxidative balance. It also triggered the down-regulation of mitochondrial fission genes, coupled with the up-regulation of mitochondrial fusion genes. Conclusion: The combination of CoQ10 and mitochondrial transplantation demonstrated a notable anti-arrhythmic effect by elevating NOx levels, reducing oxidative stress, and improving mitochondrial fission/fusion in aged rats with myocardial IRI. [ABSTRACT FROM AUTHOR]

Myocardial ischemia/reperfusion injury (MIRI) is a serious clinical complication that is caused by reperfusion therapy following myocardial infarction (MI). Mitochondria-related genes (Mito-RGs) play important roles in multiple diseases. However, the role of mitochondria-related genes in MIRI remains largely unknown. The GSE67308 dataset from the GEO database was utilized to identify MIRI-related gene modules through WGCNA. Meanwhile, differential expression analysis was conducted to identify differentially expressed genes (DEGs) in the GSE61592 dataset. Next, candidate Mito-RGs related to MIRI were screened by Venn analysis. Thereafter, a myocardial hypoxia/reperfusion (H/R) H9C2 cell model and a mouse ischemia/reperfusion (I/R) model were established to verify the expression level of glycine decarboxylase (Gldc) in MIRI in vitro and in vivo. Based on data from the GEO database, Gldc levels were notably upregulated in murine MIRI samples, compared to the control group. RT-qPCR and western blot confirmed that Gldc levels were obviously elevated in the heart of I/R mice and H/R-exposed cardiomyocytes. Moreover, the deficiency of Gldc notably increased the viability and reduced the apoptosis and inflammatory responses in H9C2 cells exposed to H/R. Meanwhile, Gldc downregulation significantly reduced p-NF-κB p65, Bax and cleaved caspase 3 levels and elevated p-Akt and Bcl-2 levels in H9C2 cells exposed to H/R. The ROC curve analysis further demonstrated that Gldc gene exhibited good diagnostic value for MIRI. Collectively, Gldc deficiency could attenuate H/R injury in cardiomyocytes in vitro through activating Akt and inactivating NF-κB signalings. These data suggested that GLDC may serve as both a diagnostic and therapeutic target for MIRI. [ABSTRACT FROM AUTHOR]

Myocardial dysfunction is a major cause of early mortality after successful cardiopulmonary resuscitation (CPR) following cardiac arrest (CA). Following the return of spontaneous circulation, myocardial ischemia–reperfusion injury can activate the NF-κB pathway, leading to the transcription of inflammatory genes that impair myocardial function. While clinical studies show hydrocortisone (HC) improves outcomes in CA patients during CPR, its specific role in modulating the NF-κB pathway is unclear. In this study, we established an in vitro model by inducing hypoxia/reoxygenation (H/R) injury in H9C2 cardiomyocytes using Na2S2O4, followed by HC treatment. The results showed that HC treatment of H/R-injured cardiomyocytes promoted proliferation, inhibited apoptosis, and suppressed the NF-κB pathway, thereby reducing interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) levels. Moreover, inhibition of the NF-κB pathway enhanced the proliferative capacity of H/R cardiomyocytes, decreased apoptosis rates, and reduced IL-6, IL-8, and TNF-α expression levels, with these effects being further amplified by HC treatment. These findings were further supported by in vivo experiments. In conclusion, our study suggests that HC may promote H/R cardiomyocyte proliferation, inhibit apoptosis, and alleviate inflammatory responses by suppressing the NF-κB pathway, providing new evidence to support its potential clinical application in CA management. [ABSTRACT FROM AUTHOR]

Myocardial ischemia-reperfusion injury (MIRI) injury is a serious health problem, which can seriously affect the recovery of patients with myocardial infarction and even lead to death. Paeoniflorin (PF) is a potential therapeutic drug to prevent reperfusion injury. However, the mechanism of PF in MIRI is not clear. Compared with other cells, cardiomyocytes have the largest number of mitochondria. Therefore, this study researched the protective mechanism of paeoniflorin pretreatment on myocardial ischemia-reperfusion injury (AMI) from the perspective of mitochondrial autophagy. Paeoniflorin was given or not given to H9C2 cells 12 h before reperfusion. Pretreatment of paeoniflorin can significantly increase the viability of H9C2 cells and inhibit the increase of ROS secretion induced by OGD/R. The increase of MDC autophagy fluorescence and mitochondrial membrane potential (MMP) suggested that the myocardial protective effect of paeoniflorin may also be related to mitochondrial autophagy. Next, we detected the related signals in the classical mitochondrial autophagy pathway of PINK1/parkin by Q-PCR and Western blots. The results showed that the pretreatment of paeoniflorin could promote the levels of SIRT1, Beclin1, PINK1, parkin and LC3, inhibit the level of P62. In order to further clarify whether paeoniflorin-induced SIRT1 activation is necessary for autophagy and its potential mechanism, we detected the autophagy level of H9C2 cells with SIRT1 inhibitor (EX527). The results showed that after pretreatment of EX527, the protective effect of paeoniflorin on oxidative damage and autophagy pathway was significantly decreased. The mechanism may relate to SIRT1-PINK1/parkin mitochondrial autophagy pathway. In summary, these results suggested that paeoniflorin may protect H9C2 cells from OGD/R damage by activating SIRT1-PINK1/parkin pathway. This provides new experimental basis for paeoniflorin in the treatment of MIRI. [Display omitted] • Paeoniflorin promotes autophagy of H9C2 cells and reduce mitochondrial dysfunction • Paeoniflorin protects cells from OGD/R-induced reperfusion injury through PINK1/parkin mitochondrial autophagy. • Paeoniflorin activates PINK1/parkin pathway by regulating the expression of SIRT1, which can protect H9C2 cells from OGD/R-induced reperfusion injury. [ABSTRACT FROM AUTHOR]

Myocardial ischemia‐reperfusion injury (MIRI) significantly worsens the outcomes of patients with cardiovascular diseases. Dexmedetomidine (Dex) is recognized for its cardioprotective properties, but the related mechanisms, especially regarding metabolic reprogramming, have not been fully clarified. A total of 60 patients with heart valve disease are randomly assigned to Dex or control group. Blood samples are collected to analyze cardiac injury biomarkers and metabolomics. In vivo and vitro rat models of MIRI are utilized to assess the effects of Dex on cardiac function, lactate production, and mitochondrial function. It is found that postoperative CK‐MB and cTNT levels are significantly lower in the Dex group. Metabolomics reveals that Dex regulates metabolic reprogramming and reduces lactate level. In Dex‐treated rats, the myocardial infarction area is reduced, and myocardial contractility is improved. Dex inhibits glycolysis, reduces lactate, and improves mitochondrial function following MIRI. Lactylation proteomics identifies that Dex reduces the lactylation of Malate Dehydrogenase 2（MDH2), thus alleviating myocardial injury. Further studies reveal that MDH2 lactylation induces ferroptosis, leading to MIRI by impairing mitochondrial function. Mechanistic analyses reveal that Dex upregulates Nuclear Receptor Subfamily 3 Group C Member 1（NR3C1) phosphorylation, downregulates Pyruvate Dehydrogenase Kinase 4 (PDK4), and reduces lactate production and MDH2 lactylation. These findings provide new therapeutic targets and mechanisms for the treatment for MIRI. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced cardiotoxicity is a significant concern in cancer treatment, as certain chemotherapeutic agents can have adverse effects on the cardiovascular system. This can lead to a range of cardiac complications, including heart failure, arrhythmias, myocardial dysfunction, pericardial complications, and vascular toxicity. Strategies to mitigate chemotherapy-induced cardiotoxicity may include the use of cardioprotective agents (e.g., dexrazoxane), dose adjustments, alternative treatment regimens, and the implementation of preventive measures, such as lifestyle modifications and the management of cardiovascular risk factors. Ginsenosides, the active compounds found in ginseng (Panax ginseng), have been studied for their potential cardioprotective effects in the context of chemotherapy-induced cardiotoxicity. In this review, we investigate the cardioprotective effect of ginsenosides in chemotherapy-induced cardiotoxicity. Ginsenosides have been shown to possess potent antioxidant properties, which can help mitigate the oxidative stress and inflammation associated with chemotherapy-induced cardiac injury. They can modulate the expression of antioxidant enzymes and reduce the production of reactive oxygen species, thereby protecting cardiomyocytes from damage. Ginsenosides can also inhibit apoptosis (programmed cell death) of cardiomyocytes, which is a key mechanism underlying chemotherapy-induced cardiotoxicity. Modulation of ion channels, improvement of lipid profiles, anti-platelet and anti-thrombotic effects, and promotion of angiogenesis and neovascularization are another important mechanisms behind potential effects of ginsenosides on cardiovascular health. Ginsenosides can improve various parameters of cardiac function, such as ejection fraction, fractional shortening, and cardiac output, in animal models of chemotherapy-induced cardiotoxicity. The cardioprotective effects of ginsenosides have been observed in preclinical studies using various chemotherapeutic agents, including doxorubicin, cisplatin, and 5-fluorouracil. However, more clinical studies are needed to fully elucidate the therapeutic potential of ginsenosides in preventing and managing chemotherapy-induced cardiotoxicity in cancer patients. [ABSTRACT FROM AUTHOR]

Despite improvements in interventional techniques leading to faster myocardial reperfusion postmyocardial infarction, there has been a significant rise in the occurrence of myocardial ischaemia/reperfusion injury (MI/RI). A deeper understanding of the underlying mechanisms of MI/RI could offer a crucial approach to reducing myocardial damage and enhancing patient outcomes. This study examined the myocardial protective properties of puerarin (PUE) in the context of MI/RI using hypoxia/reoxygenation (H/R) or ischaemia/reperfusion (I/R) injury models were employed in H9c2 cells and C57BL/6 mice. Our findings demonstrate that pretreatment with PUE effectively mitigated cardiomyocyte ferroptosis, restored redox balance, preserved mitochondrial energy production and maintained mitochondrial function following MI/RI. Furthermore, these cardioprotective effects of PUE were found to be mediated by the downregulation of voltage‐dependent anion channel 1 (VDAC1) protein. These data reveal a novel mechanism by which PUE inhibits MI/RI and reveal that this protective effect of PUE is dependent on the downregulation of VDAC1. [ABSTRACT FROM AUTHOR]

Background: Autophagy‒endoplasmic reticulum (ER) stress axis dysregulation is linked to myocardial ischemia‒reperfusion injury (MIRI), which counteracts the benefits of acute myocardial infarction (AMI) reperfusion therapy. Qingre Huoxue decoction (QRHX) improves the short- and long-term prognosis of AMI after percutaneous coronary intervention and alleviates myocardial injury in AMI rats by stimulating autophagy via the PI3K/Akt pathway. We aimed to further explore the efficacy of QRHX in treating MIRI and its regulatory relationship with FAM134B-mediated ER-phagy. Materials and methods: Rats were administered different concentrations of QRHX for 2 weeks, and then MIRI was induced. Ultra-performance liquid chromatography‒tandem mass spectrometry (UPLC‒MS) was used to examine the levels of the main pharmacological metabolites of the serum of rats treated with QRHX. H9c2 cells were pretreated with QRHX-mediating serum (QRHX-MS) for 24 h before being exposed to hypoxia/reoxygenation (H/R). The mechanisms underlying the effects of QRHX-MS were further studied via rescue experiments involving FAM134B knockdown. The myocardial infarct size, cardiac function, morphology and the expression of apoptosis-, autophagy-, and ER stress-related proteins and genes were assessed. The colocalization of autophagosomes with lysosomes and the localization of proteins involved in ER-phagy or autophagic flux was examined. Results: QRHX decreased the myocardial infarct size and oxidative stress, improved cardiac function and alleviated morphological changes in a dose-dependent manner in MIRI rats by promoting autophagic flux to inhibit ER stress and ER stress-related apoptosis, which was related to FAM134B-mediated ER-phagy, as revealed by autophagy analysis. UPLC‒MS analysis of QRHX-MS revealed 20 major active metabolites of QRHX-MS, including baicalin, cryptotanshinone, 3,4-dihydroxybenzaldehyde and caffeic acid. QRHX-MS attenuated H/R-induced cardiomyocyte injury and apoptosis by increasing autophagic flux to suppress ER stress and ER stress-related apoptotic protein and gene expression. When autophagic flux was inhibited or FAM134B was knocked down in H9c2 cells followed by QRHX-MS pretreatment, the protective effect of QRHX was partially reversed. Conclusion: QRHX alleviates myocardial injury, apoptosis and infarct size expansion in MIRI by regulating the autophagy‒ER stress axis via FAM134B-mediated ER-phagy. [ABSTRACT FROM AUTHOR]

Myocardial infarction, the most severe manifestation of coronary artery disease, is a leading cause of mortality worldwide. Here, a novel nanotherapy engineering approach is reported for enhancing therapeutic effects of mesenchymal stem cells (MSCs) on myocardial ischemia‐reperfusion (MI/R) injury. An anti‐oxidative and anti‐inflammatory nanotherapy (TPCD NP) is first fabricated. MSCs are successfully engineered with TPCD NP by endocytosis, and TPCD NP engineering does not affect stemness of MSCs. TPCD NP‐internalized MSCs (tn‐MSCs) are resistant to oxidative stress, cytotoxicity, and apoptosis induced by reactive oxygen species (ROS). Under oxidative distress, tn‐MSCs show stronger paracrine activity compared to MSCs. Consistently, tn‐MSCs effectively enhance angiogenesis of endothelial cells under pathological conditions. Also, tn‐MSCs protect cardiomyocytes from ROS‐induced cytotoxicity and apoptosis by improving mitochondrial membrane potential and regulating the p53 signaling pathway. In mice with MI/R injury, the survival time of tn‐MSCs in the injured heart is prolonged, compared to pristine MSCs. Correspondingly, tn‐MSCs more significantly reduce the infarct size, improve cardiac function, and promote cardiac remodeling in MI/R injury mice. Mechanistically, tn‐MSCs alleviate MI/R injury by attenuating oxidative stress and inflammation, inhibiting cardiomyocyte apoptosis, and promoting cardiac repair. Consequently, tn‐MSCs are promising for treating cardiovascular diseases linked to oxidative distress and inflammation. [ABSTRACT FROM AUTHOR]

This study was aimed at analyzing the ameliorative effect of empagliflozin on cardiac inflammation in sepsis-induced rats and the underlying mechanism of action. Forty male SD rats were randomly divided into four groups of 10 rats each, control group (blank control), sepsis group (rat sepsis model prepared using the cecal ligation/puncture [CLP] method, low-dose group [CLP + 10 mg/kg/day empagliflozin gavage for 8 weeks], and high-dose group [CLP + 30 mg/kg/day empagliflozin gavage for 8 weeks]). The hemodynamic indexes of each group were monitored by physiological recorder, and inflammatory cell infiltration was detected by HE staining; the expression of inflammatory factor protein, apoptosis-related protein, and NF-κB pathway-related protein were detected by Western blot; CD45+ inflammatory cell infiltration in myocardial sections was detected by immunohistochemistry; the serum myocardial injury markers were determined by enzyme-linked immunosorbent assay. The number of CD45+ inflammatory cells infiltrated into myocardial sections was measured by immunohistochemistry, and the oxidative stress response in myocardial tissue was measured by enzyme-linked immunosorbent assay. Heart rate, mean arterial blood pressure (MABP), +LVdp/dtmax, and left ventricular systolic pressure (LVSP) were lower in the sepsis group than in the control group, and –LVdp/dtmax and left ventricular end-diastolic pressure (LVEDP) were higher than in the control group (P < 0.05); the heart rate, MABP, +LVdp/dtmax, and LVSP in the high-dose group > low-dose group > sepsis group; the –LVdp/dtmax, and LVEDP in the high-dose group < low-dose group < sepsis group (P < 0.05); the number of inflammatory cell infiltration scores, CD45+ inflammatory cell infiltration and IL-1 β, IL-6, TNF-α levels, and Caspase, Bax, P50, P65, IKBKG, EGR1, and TLR9 protein expression were higher in the sepsis group than in the control group, and Bcl-2 protein expression and Bcl-2 /Bax levels were lower than those in control group (P < 0.05); the expression of IL-10, Bcl-2 protein, and Bcl-2/Bax in the high-dose group > low-dose group > sepsis group; the inflammatory cell infiltration score and IL-1β, IL-6, TNF-α, Caspase, Bax, P50, P65, IKBKG, EGR1, and TLR9 protein expression in the high-dose group < low-dose group < sepsis group (P < 0.05); CK-MB, TnT, H-FABP, HMGB-1, ROS, MDA, and GSH-Px levels were higher and SOD levels were lower in the sepsis group than in the control group (P < 0.05), and CK-MB, TnT, H-FABP, HMGB-1, ROS, MDA, and GSH-Px levels in the high-dose group < low-dose group < sepsis group, and SOD levels in the high-dose group > low-dose group > sepsis group (P < 0.05). Empagliflozin can reduce sepsis-induced cardiac inflammation, myocardial injury, oxidative stress, and inflammatory cell infiltration, improve hemodynamics, and inhibit cardiomyocyte apoptosis; its mechanism of action may be related to the regulation of the NF-κB signaling pathway by empagliflozin. [ABSTRACT FROM AUTHOR]

Ferroptosis is a regulatory cell death process pivotal in myocardial ischemia–reperfusion (I/R) injury. However, the precise mechanism underlying myocardial ferroptosis remains less known. In this study, we investigated the pathophysiological mechanisms of methylmalonic acid (MMA) associated with ferroptosis activation in cardiomyocytes after I/R. We found an increase level of MMA in patients with acute myocardial injury after reperfusion and AC16 cells under hypoxia/reoxygenation (H/R) condition. MMA treatment was found to be associated with excessive oxidative stress in cardiomyocytes, leading to ferroptosis-related myocardial injury. In mice with I/R injury, MMA treatment aggravated myocardial oxidative stress and ferroptosis, which amplified the myocardial infarct size and cardiac dysfunction. Mechanistically, MMA promoted NOX2/4 expression to increase reactive oxygen species (ROS) production in cardiomyocytes, aggravating myocardial injury. Notably, the increased ROS further activated ferroptosis by inhibiting solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression. In addition, MMA decreased the ectopic nuclear distribution of nuclear factor E2-related factor 2 (NRF2) by increasing the interaction between NRF2 and kelch-like ECH-associated protein 1 (KEAP1). This impeded the activation of GPX4/SLC7A11, downstream of NRF2, activating ferroptosis and aggravating myocardial cell injury. Collectively, our study indicates that MMA activates oxidative stress and ROS generation, which induces ferroptosis to exacerbate cardiomyocyte injury in an I/R model. These findings may provide a new perspective for the clinical treatment of I/R injury and warrant further investigation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the mechanism of emulsified isoflurane in reducing myocardial ischemia-reperfusion injury (MIRI). Materials and methods: Forty-eight healthy male Sprague-Dawley rats were randomly divided into four groups (n = 12). In the sham group (group S) and ischemia-reperfusion group (group I/R), saline (4 ml/kg/h) was administered intravenously for 30 min. In intralipid group (group L), intralipid (4 ml/kg/h) was administered intravenously. In the emulsified isoflurane group (group EI), emulsified isoflurane (4 ml/kg/h) was administered intravenously. The infusion was then discontinued for 15 min during the washout period. Apart from group S, ischemia was produced by occlusion of the left anterior descending artery (LADA) for 30 min. After 30 min of occlusion, all groups received reperfusion for two hours. Results: Creatine kinase MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Myocardial infarct size was measured using triphenyl tetrazolium chloride staining. According to the result, pretreatment with emulsified isoflurane attenuated CK-MB and cTnI concentrations (p < 0.05). And serum TNF-α and IL-6 levels and infarct size in the emulsified isoflurane group obviously decreased. An obvious decrease in the expression of the toll-like receptor-4 (TLR-4) mRNA in group EI was observed compared with group I/R. Discussion and conclusion: Emulsified isoflurane precondition had a potent cardioprotective effect against myocardial ischemia-reperfusion injury. The mechanisms involved may be related to the decrease in the expression of TLR-4 and the reduced inflammatory response. [ABSTRACT FROM AUTHOR]

Ventricular fibrillation (VF)-induced cardiac arrest frequently complicates ST-segment elevation myocardial infarction (STEMI). Although larger infarct sizes (IS) correlate with a higher risk of VF, the influence of VF itself on IS has remained poorly investigated. To address this knowledge gap, we analyzed the effect of VF on IS in patients and two experimental models. From a prospective cohort, 30 STEMI patients with VF were matched 1:2 with STEMI patients without VF on the common determinants of IS. The primary endpoint was IS, assessed using the 48-h area under the curve (AUC) for troponin. We also compared IS in pigs with/without spontaneous VF during STEMI (n = 15/group), and in an isolated rat heart model of myocardial infarction with/without electrically induced VF (n = 7/group). After matching, the patient characteristics, including the area at risk (AR), were similar. IS was 33% lower in the VF group compared to the control group (troponin AUC 1.6 [0.5–3.3] 106 arbitrary units vs. 2.4 [0.9–4.1] 106 arbitrary units; p < 0.05), but infarct scar size (assessed using MRI and ECG) did not differ between the groups at 1 and 6 months. In both experimental models, IS, expressed as a percentage of AR, was lower (p < 0.05) in the VF group than in the control group. When common determinants of IS are comparable, VF occurring prior to myocardial infarction reperfusion appears to be associated with smaller IS. Nevertheless, this finding, observed under specific experimental conditions and in a highly selected group of patients, was not associated with reduced infarct scar size. Registration (HIBISCUS-STEMI cohort): ClinicalTrials.gov NCT05794022. [ABSTRACT FROM AUTHOR]

The editorial discusses the history and challenges of cardioprotection research, focusing on the CAESAR and IMPACT networks. CAESAR, established 15 years ago, set standards for rigorous preclinical studies, while IMPACT, a multinational network, aims to evaluate infarct-sparing strategies in pigs. The IMPACT study on ischemic preconditioning shows promise but highlights the need for standardized protocols and large sample sizes. The editorial emphasizes the importance of rigorous research in advancing cardioprotection and calls for industry support to ensure the network's survival. [Extracted from the article]

Objectives: Intestinal ischemia-reperfusion (I/R) injury is a multifactorial and complex clinical pathophysiological process. Current research indicates that the pathogenesis of intestinal I/R injury involves various mechanisms, including ferroptosis. Methane saline (MS) has been demonstrated to primarily exert anti-inflammatory and antioxidant effects in I/R injury. In this study, we mainly investigated the effect of MS on ferroptosis in intestinal I/R injury and determined its potential mechanism. Methods: In vivo and in vitro intestinal I/R injury models were established to validate the relationship between ferroptosis and intestinal I/R injury. MS treatment was applied to assess its impact on intestinal epithelial cell damage, intestinal barrier disruption, and ferroptosis. Results: MS treatment led to a reduction in I/R-induced intestinal epithelial cell damage and intestinal barrier disruption. Moreover, similar to treatment with ferroptosis inhibitors, MS treatment reduced ferroptosis in I/R, as indicated by a decrease in the levels of intracellular pro-ferroptosis factors, an increase in the levels of anti-ferroptosis factors, and alleviation of mitochondrial damage. Additionally, the expression of Nrf2/HO-1 was significantly increased after MS treatment. However, the intestinal protective and ferroptosis inhibitory effects of MS were diminished after the use of M385 to inhibit Nrf2 in mice or si-Nrf2 in Caco-2 cells. Discussion: We proved that intestinal I/R injury was mitigated by MS and that the underlying mechanism involved modulating the Nrf2/HO-1 signaling pathway to decrease ferroptosis. MS could be a promising treatment for intestinal I/R injury. [ABSTRACT FROM AUTHOR]

Ginseng (Panax ginseng C. A. Meyer), a traditional Chinese medicine, and the rare ginsenosides contained in it have various physiological activities. 25-OH-PPT (T19) is a rare natural dammarane-type ginseng sapogenin. Pharmacological studies have shown that T19 has good hypoglycemic, antioxidant, and anti-inflammatory activities. In the research, we optimized the T19 enrichment process and explored the potential mechanism of T19 in myocardial oxidative stress. Firstly, we studied a hydrolysis process on ginseng stems and leaves ginsenosides. Optimization factors include acid types, acid concentrations, ultrasound time, and ultrasound temperature. To develop safer preparation conditions more suitable for production scaleup, we studied the difference in hydrolysis between inorganic acid and food acids. The results show that using hydrochloric acid to hydrolyze ginsenosides in ginseng stems and leaves can increase the content of T19 to 12.16%. When using edible citric acid, the maximum content of T19 is 1.9%. However, using citric acid for hydrolysis has higher safety and non-toxic properties. Meanwhile, the myocardial protective effect of T19 was evaluated, indicating that T19 could effectively reduce isoproterenol (ISO)-induced oxidative stress injury by reducing the levels of LDH and CK-MB and regulating the contents of antioxidant enzymes SOD, lipid peroxidation product MDA, and non-enzymatic antioxidant GSH in cardiomyocytes. Further study demonstrated that regulation of fibrosis markers Collagen I, Collagen III, and α-SMA was involved in the potential mechanism of T19 efficiency. [ABSTRACT FROM AUTHOR]

2′-Hydroxycinnamaldehyde (HCA), a natural product isolated from the bark of Cinnamomum cassia, has anti-inflammatory and anti-tumor activities. In this study, we explored whether HCA preconditioning could protect the heart against ischemia/reperfusion (I/R)-induced oxidative injury through cytosolic Bcl-2-associated athanogene 3 (BAG3) upregulation. In vivo HCA preconditioning was performed intraperitoneally in adult male Wistar rats (50 mg/kg body weight) three times/week for 2 weeks before cardiac I/R injury. The animals were divided into sham control (sham), I/R, and HCA preconditioning plus I/R (HCA+I/R) groups. We examined left ventricular pressure cardiac hemodynamics, the microcirculation, electrocardiograms, infarct size, and oxidative stress and performed Western blots, immunohistochemistry, and cytokine array assays. HCA pretreatment, via BAG3 overexpression, inhibited H2O2-induced H9c2 cell death. Cardiac I/R injury increased ST-segment elevation, left ventricular end-diastolic pressure, infarct size, myocardial disruption, tissue edema, erythrocyte accumulation, leukocyte infiltration, reactive oxygen species, malondialdehyde, 8-isoprostane, caspase 3-mediated apoptosis, 4HNE/GPX4-mediated ferroptosis, and fibrosis but decreased the microcirculation, cytosolic BAG3, and Beclin-1/LC3 II-mediated autophagy in the I/R hearts. HCA preconditioning significantly decreased these oxidative injuries by increasing cardiac cytosolic BAG3 and Nrf2/HO-1 signaling. HCA preconditioning significantly decreased cardiac I/R-enhanced mitochondrial fission DRP1 expression. Our data suggest that HCA preconditioning can efficiently improve myocardial I/R injury-induced cardiac dysfunction, apoptosis, ferroptosis, mitochondrial fission, and autophagy inhibition through cardiac BAG3 and Nrf2/HO-1 upregulation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Ischemia-reperfusion (I/R) injury is a process in which impaired perfusion is restored by restoring blood flow and tissue recirculation. Nanomedicine uses cutting-edge technologies that emerge from interdisciplinary influences. In the literature, there are very few in vivo and in vitro studies on how cerium oxide (CeO2) affects systemic anti-inflammatory response and inflammation. Therefore, in our study, we aimed to investigate whether CeO2 administration has a protective effect against myocardial I/R injury in the liver and kidneys. Materials and Methods: Twenty-four rats were randomly divided into four groups after obtaining approval from an ethics committee. A control (group C), cerium oxide (group CO), IR (group IR), and Cerium oxide-IR (CO-IR group) groups were formed. Intraperitoneal CeO2 was administered at a dose of 0.5 mg/kg 30 min before left thoracotomy and left main coronary (LAD) ligation, and myocardial muscle ischemia was induced for 30 min. After LAD ligation was removed, reperfusion was performed for 120 min. All rats were euthanized using ketamine, and blood was collected. Liver and kidney tissue samples were evaluated histopathologically. Serum AST (aspartate aminotransferase), ALT (alanine aminotransaminase), GGT (gamma-glutamyl transferase), glucose, TOS (Total Oxidant Status), and TAS (Total Antioxidant Status) levels were also measured. Results: Necrotic cell and mononuclear cell infiltration in the liver parenchyma of rats in the IR group was observed to be significantly increased compared to the other groups. Hepatocyte degeneration was greater in the IR group compared to groups C and CO. Vascular vacuolization and hypertrophy, tubular degeneration, and necrosis were increased in the kidney tissue of the IR group compared to the other groups. Tubular dilatation was significantly higher in the IR group than in the C and CO groups. TOS was significantly higher in all groups than in the IR group (p < 0.0001, p < 0.0001, and p = 0.006, respectively). However, TAS level was lower in the IR group than in the other groups (p = 0.002, p = 0.020, and p = 0.031, respectively). Renal and liver histopathological findings decreased significantly in the CO-IR group compared to the IR group. A decrease in the TOS level and an increase in the TAS level were found compared to the IR group. The AST, ALT, GGT, and Glucose levels are shown. Conclusions: CeO2 administered before ischemia-reperfusion reduced oxidative stress and ameliorated IR-induced damage in distant organs. We suggest that CeO2 exerts protective effects in the myocardial IR model. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human umbilical cord mesenchymal stem cell-derived exosomes are involved in multiple injury repair processes, and the effects and the specific mechanisms of renal ischemia/reperfusion injury have not been fully elucidated. OBJECTIVE: To investigate the molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes in the treatment of renal ischemia/ reperfusion injury. METHODS: (1) Human umbilical cord mesenchymal stem cells were cultured and exosomes were obtained and identified using an exosome extraction kit. (2) The distribution of exosomes in the kidney of mice with renal ischemia/reperfusion injury was examined by intravital fluorescence imaging. (3) Thirty C57/ BL6 male mice were divided into five groups according to the random number table method: sham operation group, renal ischemia/reperfusion group, sham operation group+Compound C group, renal ischemia/reperfusion+exosome group (exosome group), and renal ischemia/reperfusion+exosome+Compound C group (exosome+Compound C group), with 6 mice in each group. Except the sham operation group, bilateral renal pedicles were clamped for 45 minutes and a mouse model of renal ischemia/reperfusion injury was established after 24 hours of reperfusion. In sham operation+Compound C group and exosome+Compound C group, AMPK inhibitor Compound C was intraperitoneally injected 30 minutes before model establishment. In the exosome group and exosome+Copmpound C group, exosomes were injected through the tail vein 15 minutes before renal pedicle clipping. The levels of serum creatinine and urea nitrogen, interleukin 6, and tumor necrosis factor α in renal tissue, and the expression of apoptosis-related factors in renal tissue were detected after 24 hours of reperfusion in each group. RESULTS AND CONCLUSION: (1) Human umbilical cord mesenchymal stem cell exosomes had the typical tea tray morphology, with the diameter distribution in the range of 40-160 nm, and expressed the specific marker membrane protein of exosome surface. (2) Murine kidneys after renal ischemia/reperfusion injury were more likely to gather human umbilical cord mesenchymal stem cell exosomes compared with the sham operation group. (3) Exosome pretreatment reduced renal injury and the level of renal cell apoptosis in mice treated with renal ischemia/reperfusion injury. Moreover, this protective effect could be reversed by AMPK inhibitors. These findings verify that human umbilical cord mesenchymal stem cell-derived exosomes exerting a protective effect on renal ischemia/reperfusion injury may be related to the activation of the AMPK/YAP1 pathway to antiapoptosis. [ABSTRACT FROM AUTHOR]

Background: High-density lipoprotein (HDL) protects against myocardial ischemia-reperfusion (I/R) injury. Mammalian target of rapamycin complexes 1 and 2 (mTORC1 and mTORC2) play opposing roles in protecting against I/R injury, whereby mTORC1 appears to be detrimental while mTORC2 is protective. However, the role of HDL and mTORC signaling in protecting against I/R in hypertensive rodents is not clearly understood. In this study, we investigated the involvement of mTORC1 and mTORC2 in HDL-mediated protection against myocardial I/R injury in normotensive Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Methods: Hearts from WKY and SHR were subjected to I/R injury using a modified Langendorff system. Hemodynamics data were collected, and infarct size was measured. Rapamycin and JR-AB2-011 were used to test the role of mTORC1 and mTORC2, respectively. MK-2206 was used to test the role of Akt in HDL-mediated cardiac protection. The expression levels and the activation states of mediators of mTORC1 and mTORC2 signaling and myocardial apoptosis were measured by immunoblotting and/or enzyme-linked immunosorbent assay (ELISA). Results: HDL protected hearts from WKY and SHR against I/R injury as indicated by significant improvements in cardiac hemodynamics and reduction in infarct size. HDL induced greater protection in WKY compared to SHR. HDL treatment attenuated mTORC1 signaling in WKY by reducing the phosphorylation of P70S6K (mTORC1 substrate). In SHR however, HDL attenuated mTORC1 signaling by reducing the levels of phospho-mTORC1, Rag C (mTORC1 activator), and phospho-PRAS40 (mTORC1 inhibitor). HDL increased the phosphorylation of mTORC2 substrate Akt, specifically the Akt2 isoform in SHR and to a greater extent in WKY. HDL-induced protection was abolished in the presence of Akt antagonist and involved attenuation of GSK, caspases 7 and 8 activation, and cytochrome C release. Conclusion: HDL mediates cardiac protection via attenuation of mTORC1, activation of mTORC2-Akt2, and inhibition of myocardial apoptosis. HDL regulates mTORC1 and mTORC2 signaling via distinct mechanisms in normotensive and hypertensive rats. HDL attenuation of mTORC1 and activation of mTORC2-Akt2 signaling could be a mechanism by which HDL protects against myocardial I/R injury in hypertension. [ABSTRACT FROM AUTHOR]

Despite the widespread adoption of emergency coronary reperfusion therapy, reperfusion‐induced myocardial injury remains a challenging issue in clinical practice. Following myocardial reperfusion, S100A8/A9 molecules are considered pivotal in initiating and regulating tissue inflammatory damage. Effectively reducing the S100A8/A9 level in ischemic myocardial tissue holds significant therapeutic value in salvaging damaged myocardium. In this study, HA (hemagglutinin)‐ and RAGE (receptor for advanced glycation end products)‐ comodified macrophage membrane‐coated siRNA nanoparticles (MMM/RNA NPs) with siRNA targeting S100A9 (S100A9‐siRNA) are successfully prepared. This nanocarrier system is able to target effectively the injured myocardium in an inflammatory environment while evading digestive damage by lysosomes. In vivo, migration of MMM/RNA NPs to myocardial injury lesions is confirmed in a myocardial ischemia‐reperfusion injury (MIRI) mouse model. Intravenous injection of MMM/RNA NPs significantly reduced S100A9 levels in serum and myocardial tissues, further decreasing myocardial infarction area and improving cardiac function. Targeted reduction of S100A8/A9 by genetically modified macrophage membrane‐coated nanoparticles may represent a new therapeutic intervention for MIRI. [ABSTRACT FROM AUTHOR]

Fibronectin type III domain containing 4 (FNDC4) is highly homologous with FNDC5, which possesses various cardiometabolic protective functions. Emerging evidence suggests a noteworthy involvement of FNDC4 in fat metabolism and inflammatory processes. This study aimed to characterize the role of FNDC4 in myocardial ischemia/reperfusion (MI/R) injury and decrypt its underlying mechanisms. MI/R models of mice were established to investigate the alteration of FNDC4 in plasma and myocardium. We observed that plasma FNDC4 in MI/R-injury mice and patients experiencing acute myocardial infarction were both significantly reduced as opposed to their respective controls. Likewise, FNDC4 expression of myocardium decreased markedly in MI/R mice compared to the sham-operated group. Mice of FNDC4 knockout and myocardial overexpression were further introduced to elucidate the role of FNDC4 in MI/R injury by detecting cardiomyocyte apoptosis, myocardial infarct size, and cardiac function. Ablation of FNDC4 exacerbated cardiac dysfunction, increased myocardial infarction area and cardiomyocyte apoptosis when matched with wild-type mice post-MI/R. In contrast, FNDC4 overexpression through intramyocardial injection of rAAV9-Fndc4 significantly ameliorated cardiac function, reduced myocardial infarction area and cardiomyocyte apoptosis compared to sham group. Additionally, hypoxia-reoxygenation (H/R) was used to induce cardiomyocyte apoptosis, and to further elucidate the direct effects of FNDC4 on cardiomyocytes in vitro , and the results demonstrated that neonatal rat ventricular cardiomyocytes overexpressing FNDC4 showed less H/R-induced apoptosis, as evidenced by cleaved caspase 3 expression, TUNEL staining and flow cytometry. By performing RNA-seq analysis followed by cause-effect analysis, ERK1/2-Nrf2 pathway-mediated antioxidative effects were responsible for the protective roles of FNDC4 on cardiomyocytes. In summary, FNDC4 exerts cardioprotection against MI/R injury predominantly through mitigating oxidative stress responses and reducing cardiomyocyte apoptosis. These insights solidify the proposition of FNDC4 as a potential therapeutic aim for tackling MI/R damage. [Display omitted] • Cardiac and plasma FNDC4 was downregulated in mice with myocardial ischemia/reperfusion injury (MI/R). • FNDC4 deficiency exacerbates cardiac dysfunction, whereas FNDC4 overexpression leads to marked improvements in MI/R mice. • ERK1/2-Nrf2 was identified to mediate the anti-oxidative stress and anti-apoptotic effects of FNDC4 in cardiomyocytes. [ABSTRACT FROM AUTHOR]

Introduction: Acute aortic occlusion (AAO) is a rare vascular emergency with significant associated morbidity and mortality Methods: This case report discusses a 39‐year‐old gentleman with methamphetamine‐associated cardiomyopathy (MACM) who presented with bilateral lower limb ischaemia. A POCUS was performed to rapidly evaluate the patient on arrival, which demonstrated AAO. A literature review was conducted to identify similar cases where AAO was detected by POCUS. Results: POCUS showed a left ventricular thrombus (LVT), an embolus in the distal abdominal aorta and no flow distal to the embolus, which is consistent with AAO. The patient was successfully reperfused and had a good outcome after a timely diagnosis and management. Discussion: This case report outlines a rare pathology in an uncommon age group where POCUS can expedite diagnosis and management. Conclusion: POCUS is a valuable tool, which can expedite and facilitate rapid revascularisation of AAO. [ABSTRACT FROM AUTHOR]

Objective: To investigate protective effect of wogonin on myocardial ischemia/reperfusion (MI/R) injury in rats, and to analyze its potential mechanism. Methods: SD rats were randomly separated into sham operation group, MI/R group, trimetazi- dine group (10 mg/kg), wogonin low, medium and high doses groups (5, 10, 20 mg/kg), with 12 rars per group. MI/R model was established by ligation of left anterior descending coronary artery for 30 min and reperfusion for 24 h. Echocardiography was applied to detect cardiac function in rats, ELISA was applied to detect activities of serum lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) and levels of TNF-a, 1L-6 and IL-l(i in rats; TTC staining was applied to detect myocardial infarct size; HE staining was applied to detect myocardial histo pathological changes; TUN EL staining was applied to detect apoptosis level of cardiomyocytes; immunohistochemistry (IHC) method was applied to detect expression of nuclear factor-KB (NF-KB) p65 in myocardial tissue; Western blot was applied to detect myocardial apoptosis and expressions of NF-KB/mitogen-activated protein kinase (MAPK) pathway- related proteins. Results:Compared with sham operation group, LVESD, LVEDD, serum CK-MB and LDH activities, levels of IL-6, IL-1β and TNF-α, myocardial infarction area percentage, myocardial cell apoptosis rate, protein level of Bax, expression of nuclear NF-κB p65, and Cleaved-Caspase-3/Caspase-3, p-P38 MAPK/P38 MAPK in MI/R group were obviously increased, EF, FS and protein levels of Bcl-2 were obviously decreased (P<0.05), myocardial fibers were disordered, and a large number of inflammatory cells were infiltrated; compared with MI/R group, LVESD, LVEDD, serum CK-MB and LDH activities, levels of IL-6, IL-1β and TNF-α, myocardial infarction area percentage, myocardial cell apoptosis rate, protein level of Bax, expression of nuclear NF-KB p65, and Cleaved-Caspase-3/Caspase-3 and p-P38 MAPK/P38 MAPK in trimetazidine group and wogonin high, medium and low doses groups were obviously decreased, EF, FS and protein levels of Bcl-2 were obviously increased (P<0.05), myocardial inflammatory cell infiltration and muscle fiber fragmentation were reduced in a dose-dependent manner. Conclusion: Wogonin may improve MI/R injury in rats by inhibiting NF-κB/MAPK signaling pathway, inhibiting inflammatory response and cardiomyocyte apoptosis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ginsenoside fraction from Panax ginseng decreased the acetylated protein levels of spliceosome in cardiomyocytes. • Ginsenoside Rb2 inhibited SF3A2 acetylation at lysine 10 to promote mitochondrial function against myocardial ischemic/reperfusion injury. • Ginsenoside Rb2 promoted Fscn1 alternative splicing to enhance mitochondrial respiration. • The decreased acetylation of SF3A2 (K 10) by ginsenoside Rb2 was mediated by p300 inhibition. Ginsenosides (GS) derived from Panax ginseng can regulate protein acetylation to promote mitochondrial function for protecting cardiomyocytes. However, the potential mechanisms of GS for regulating acetylation modification are not yet clear. This study aimed to explore the potential mechanisms of GS in regulating protein acetylation and identify ginsenoside monomer for fighting myocardial ischemia-related diseases. The 4D-lable free acetylomic analysis was employed to gain the acetylated proteins regulated by GS pretreatment. The co-immunoprecipitation assay, immunofluorescent staining, and mitochondrial respiration measurement were performed to detect the effect of GS or ginsenoside monomer on acetylated protein level and mitochondrial function. RNA sequencing, site-specific mutation, and shRNA interference were used to explore the downstream targets of acetylation modificationby GS. Cellular thermal shift assay and surface plasmon resonance were used for identifying the binding of ginsenoside with target protein. In the cardiomyocytes of normal, oxygen glucose deprivation and/or reperfusion conditions, the acetylomic analysis identified that the acetylated levels of spliceosome proteins were inhibited by GS pretreatment and SF3A2 acetylation at lysine 10 (K 10) was significantly decreased as a potential target of GS. Ginsenoside Rb2 was identified as one of the active ginsenoside monomers for reducing the acetylation of SF3A2 (K 10), which enhanced mitochondrial respiration against myocardial ischemic injury in in vivo and in vitro experiments. RNA-seq analysis showed that ginsenoside Rb2 promoted alternative splicing of mitochondrial function-related genes and the level of fascin actin-bundling protein 1 (Fscn1) was obviously upregulated, which was dependent on SF3A2 acetylation. Critically, thermodynamic, kinetic and enzymatic experiments demonstrated that ginsenoside Rb2 directly interacted with p300 for inhibiting its activity. These findings provide a novel mechanism underlying cardiomyocyte protection of ginsenoside Rb2 by inhibiting p300-mediated SF3A2 acteylation for promoting Fscn1 expression, which might be a promising approach for the prevention and treatment of myocardial ischemic diseases. [ABSTRACT FROM AUTHOR]

Introduction. Ischemia followed by reperfusion in organ transplantations can lead to ischemia-reperfusion (I-R) injury, which is associated with oxidative stress and inflammatory responses. Alpha-pinene is an organic terpene with well-known antioxidant, anti-inflammatory, and anti-apoptotic properties. This study examines the preventive effects of alpha-pinene against renal I-Rinduced kidney dysfunction, oxidative and inflammatory status, apoptosis, and histopathology changes. Methods. Forty-two adult male Wistar rats weighting 200-250 gr were divided into six groups (n = 7): Control, Right Nephrectomy, Ischemia-Reperfusion (45 min ischemia and 24 h reperfusion), and I-R + three different doses of alpha-pinene (2.5, 5, and 10 mg/kg) 24 hours and just before induction of ischemia through gavage. After 24 hours, urine, serum, and the remaining kidney were collected for biochemical and tissue analysis. Results. Renal I-R caused kidney damage indicated by a significant decrease in creatinine clearance, induction of oxidative stress, increased inflammatory cytokines, and histopathological injuries. Alpha-pinene significantly improved the damage by restoring the changes toward the control group. Alpha-pinene, in the effective dose (2.5 mg/kg), reduced the levels of Bax, Bcl-2, TNF-a, and IL1ß and contributed to regenerating tissue damage following renal I-R. Conclusions. Aalpha-pinene has been able to reduce the complications due to its antioxidant, anti-inflammatory, and anti-apoptotic properties. It is suggested that it can be used as a pretreatment in reducing renal complications in renal transplantation. [ABSTRACT FROM AUTHOR]

Objectives: We compared the cardioprotective capacity of Del Nido cardioplegia and warm Calafiore blood cardioplegia in an experimental setting during 90 min of ischaemia. Methods: 20 adult and 20 senescent rat hearts were isolated and mounted on a blood-perfused, pressure-controlled Langendorff apparatus. After a stabilization period, cardiac arrest (90 min) was induced by the administration of either Calafiore (Cala) or Del Nido solution (DNS). While Cala was given warm and intermittently, DNS was given as a cold single shot. During 90 min of reperfusion, cardiac function and metabolism were evaluated and biomarker levels were measured. After the end of the experiment, hearts were prepared for electronmicroscopic investigation. Results: Hearts exposed to Cala recovered faster during reperfusion compared with hearts administered DNS (Cala vs DNS at 30 min reperfusion: left ventricular developed pressure 72, SD: 22% of baseline (BL) versus 40, SD: 32% of BL, p <.001, and positive derived left ventricular pressure over time was better in both adult and senescent Cala groups (96, SD: 31% of BL) than in the DNS groups (39, SD: 27% of BL, p <.001). Ischaemic contractures were seen in the DNS groups starting after 30 min of ischaemia, whereas no rise in diastolic pressure was observed for the Cala groups. Accordingly, lactate production was higher after DNS (1.23 mg/dl (SD 0.87) than after Cala (0.33 mg/dl (SD 0.68), p =.015) at the beginning of reperfusion. Troponin I levels at the end of reperfusion were higher after DNS treatment in adult hearts (DNS: 287.9 SD: 147.7 ng/mL vs Cala 91.2: SD: 94.7 ng/mL, p =.02) and in senescent hearts (DNS: 376.5 (SD: 162.8) ng/ml versus Cala 104.7 (SD: 150.2) ng/ml, p =.025). Electron microscopy showed that the cellular oedema index was higher in adult DNS hearts (1.2 ± 0.2) than in adult Cala hearts (0.8 ± 0.1, p =.012), whereas the VS ratio was similar (0.18 ± 0.01 vs 0.17 ± 0.03). Conclusion: Calafiore cardioplegia offers better myocardial protection from ischaemia/reperfusion-related damage in isolated perfused adult and senescent rat hearts than Del Nido cardioplegia. [ABSTRACT FROM AUTHOR]

Revascularization procedures such as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are crucial to restore blood flow to the heart and are used in the treatment of myocardial infarction (MI). However, these techniques are known to cause myocardial reperfusion injury in the ischemic heart. The present study aims to mimic ischemia–reperfusion injury in vitro on primary human cardiomyocytes (HCMs) and use the established injury model to study the rescue mechanism of skeletal muscle cell (SkM)-seeded electrospun fiber-coated human amniotic membrane scaffold (EF–HAM) on injured cardiomyocytes through paracrine secretion. An in vitro ischemia–reperfusion injury model was established by exposing the HCM to 5 h of hypoxia, followed by a 6 h reoxygenation period. Six different conditioned media (CM) including three derived from SkM-seeded EF–HAMs were introduced to the injured cells to investigate the cardioprotective effect of the CM. Cell survival analysis, caspase-3 and XIAP expression profiling, mitochondrial membrane potential analysis, and measurement of reactive oxygen species (ROS) were conducted to evaluate the outcomes of the study. The results revealed a significant increase in the viability of HCM exposed to H/R injury by 77.2% (p < 0.01), 111.8% (p < 0.001), 68.7% (p < 0.05), and 69.5% (p < 0.05) when supplemented with HAM CM, EF–HAM 3 min CM, EF–HAM 5 min CM, and EF–HAM 7 min CM, respectively. Furthermore, CM derived from SkM-seeded EF–HAM scaffolds positively impacted hypoxia-/reoxygenation-induced changes in caspase-3 expression, mitochondrial membrane potential, and reactive oxygen species generation, but not in XIAP expression. These findings suggest that EF–HAM composite scaffolds can exert antiapoptotic and cardioregenerative effects on primary human cardiomyocytes through the paracrine mechanism. [ABSTRACT FROM AUTHOR]

Organic nanocrystals, particularly those composed of conjugated molecules, hold immense potential for various applications. However, their practical utility is often hindered by the challenge of achieving stable aqueous dispersions, which are essential for biological compatibility and effective delivery. This study introduces a novel and versatile strategy for preparing stable aqueous organic nanocrystals using a modified reprecipitation method. We demonstrate the broad applicability of this approach by successfully preparing a diverse library of nanocrystals from 27 conjugated molecules. Our findings reveal a charge-balanced aggregation mechanism for nanocrystal formation, highlighting the crucial role of surface charge in controlling particle size and stability. Based on this mechanism, we establish a comprehensive molecular combination strategy that directly links molecular properties to colloidal behaviour, enabling the straightforward prediction and preparation of stable aqueous dispersions without the need for excipients. This strategy provides a practical workflow for tailoring the functionality of these nanocrystals for a wide range of applications. To illustrate their therapeutic potential, we demonstrate the enhanced efficacy of these nanocrystals in treating acute ulcerative colitis, myocardial ischemia/reperfusion injury, and cancer in mouse models. This work paves the way for developing next-generation nanomaterials with tailored functionalities for diverse biomedical applications. [Display omitted] • Bridging Disciplines: This research bridges crystal engineering and colloid science by achieving aqueous stability of organic nanocrystals. • New Design Rules: Charge-balanced aggregation links molecular properties to colloidal behaviour for stable nanocrystals. • Predictive Strategy: A strategy for identifying suitable molecular combinations for aqueous organic nanocrystals. • Practical Workflow: A practical workflow for preparing diverse aqueous organic nanocrystals. • Functional Control & Applications: Diverse molecular combinations enable control over nanocrystal functionality for bioapplications. [ABSTRACT FROM AUTHOR]

Background/Aim: Although it has been reported that different molecules are effective in preventing ischemia-reperfusion (I/R) injury, the most effective treatment is still unknown. Materials and Methods: The rats were divided into four groups of eight rats each. Group C: 1 ml intraperitoneal (IP) isotonic + laparotomy + IP 2 ml isotonic +I/R. Group D: 100 μg kg-1/1 ml IP dexmedetomidine + laparotomy + IP 2 ml isotonic +I/R. Group L: 1 ml IP isotonic + laparotomy + IP levobupivacaine (2.5 mg kg-1/2 ml) +I/R. Group DL: 100 μg kg-1/1 ml IP dexmedetomidine + laparotomy + IP levobupivacaine (2.5 mg kg-1/2 ml) +I/R. Brain, heart, lung, and liver tissue samples were collected for histopathological examination. Biochemically, levels of aspartate amino transaminase, alanine amino transaminase, serum glucose, total antioxidant status (TAS), total oxidant status, ischemia modified albumin, and malondialdehyde were measured in blood samples. Results: Group D mean blood TAS levels were found to be statistically significantly higher than those in Group C and Group L (p=0.037, p=0.048 respectively). Group DL oxidative stress index (OSI) value was found to be statistically significantly lower than that of Group C (p=0.010). Conclusion: Both dexmedetomidine and levobupivacaine demonstrated protective effects in I/R injury. When used in combination, the effects of these treatments were further enhanced, reaching statistical significance. As our literature review found no studies on the combined use of dexmedetomidine and levobupivacaine in I/R injury, it is anticipated that supporting these results with clinical studies may significantly contribute to clinical practice. [ABSTRACT FROM AUTHOR]

Background/Objectives: Treatment of patients with myocardial ischemic diseases crucially involves cardiac reperfusion (CR). However, oxidative stress and tissue lesions caused by CR may also lead to lethal complications, such as arrythmias and vasoplegic syndrome (VS). Although methylene blue (MB) has long been used to treat VS due to cardiac ischemia and reperfusion (CIR) and/or surgery because of its vascular effects, MB's effects on the heart are unclear. Therefore, we investigated the potential cardioprotective or arrhythmogenic effects of MB in an animal model of CIR. To this end, 12–16-week-old male Wistar rats were divided into four experimental groups: (a) rats subjected to SHAM surgery with no ischemia; (b) rats subjected to CIR and treated with a vehicle (SS + CIR); and (c) rats subjected to CIR and treated with 2 mg/kg i.v. MB before ischemia (MB + ISQ) or (d) after ischemia but before reperfusion (ISQ + MB). An ECG analysis was used to evaluate the incidence of ventricular arrhythmias (VAs), atrioventricular blocks (AVBs), and lethality (LET) resulting from CIR. After CIR, rat hearts were removed for histopathological analysis and lipid hydroperoxide (LH) measurements. Results: The incidence of VA, AVB, and LET was significantly increased in the MB + ISQ group (VA = 100%; AVB = 100%; LET = 100%) but significantly reduced in the ISQ + MB group (VA = 42.8%; AVB = 28.5%; LET = 21.4%) compared with the SS + CIR group (VA = 85.7%; AVB = 71.4%; LET = 64.2%). LH concentration was significantly reduced in both MB-treated groups, but myocardial injuries were increased only in the MB + ISQ group when compared with the SS + CIR group. Conclusions: These results indicate that MB produces a biphasic effect on CIR, with cardiotoxic effects when administered before cardiac ischemia and cardioprotective effects when administered after ischemia but before cardiac reperfusion. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases are the leading cause of death worldwide, including the United Arab Emirates. Ischemia–reperfusion (IR) injury results in the death of cardiac myocytes that were viable immediately before myocardial reperfusion. We aim to investigate the role of galectin-3 (Gal-3) in autophagy during ischemia–reperfusion injuries. Methods: Male C57B6/J and Gal-3 knockout (KO) mice were used for the murine model of IR injury. Heart samples and serum were collected 24 h post-IR and were processed for immunohistochemical and immunofluorescent labeling and an enzyme-linked immunosorbent assay. Results: There was a significant increase in left ventricle (LV) concentrations of Gal-3 in Gal-3 wild-type mice compared to sham mice. There were significantly higher concentrations of LV autophagy proteins and phospho-AMPK in IR Gal-3 KO mice than in IR Gal-3 wild-type mice, compared to lower concentrations of LV phospho-mTOR and p62 in IR Gal-3 KO than in IR wild-type mice. Antioxidant activities were higher in the LVs of IR Gal-3 wild-type mice, while oxidative stress was higher in the LVs of IR Gal-3 KO mice. Conclusions: Our study supports the interaction of Gal-3 with autophagy proteins, oxidative stress, and antioxidant proteins and demonstrates that the absence of Gal-3 can enhance autophagy in the heart after IR injury. [ABSTRACT FROM AUTHOR]

Uremic cardiomyopathy (UC) represents a complex syndrome characterized by different cardiac complications, including systolic and diastolic dysfunction, left ventricular hypertrophy, and diffuse fibrosis, potentially culminating in myocardial infarction (MI). Revascularization procedures are often necessary for MI management and can induce ischemia reperfusion injury (IR). Despite this clinical relevance, the role of fine particulate matter (PM2.5) in UC pathology and the underlying subcellular mechanisms governing this pathology remains poorly understood. Hence, we investigate the impact of PM2.5 exposure on UC susceptibility to IR injury. Using a rat model of adenine-induced chronic kidney disease (CKD), the animals were exposed to PM2.5 at 250 µg/m3 for 3 h daily over 21 days. Subsequently, hearts were isolated and subjected to 30 min of ischemia followed by 60 min of reperfusion to induce IR injury. UC hearts exposed to PM2.5 followed by IR induction (Adenine + PM_IR) exhibited significantly impaired cardiac function and increased cardiac injury (increased infarct size and apoptosis). Analysis at the subcellular level revealed reduced mitochondrial copy number, impaired mitochondrial bioenergetics, decreased expression of PGC1-α (a key regulator of mitochondrial biogenesis), and compromised mitochondrial quality control mechanisms. Additionally, increased mitochondrial oxidative stress and perturbation of the PI3K/AKT/AMPK signaling axis were evident. Our findings therefore collectively indicate that UC myocardium when exposed to PM2.5 is more vulnerable to IR-induced injury, primarily due to severe mitochondrial impairment. [ABSTRACT FROM AUTHOR]

This research focused on investigating the effects of sevoflurane (Sev) on myocardial autophagy levels after myocardial ischemia reperfusion (I/R) injury via the microRNA-542-3p (miR-542-3p)/ADAM9 axis. Mice underwent 30 min occlusion of the left anterior descending coronary (LAD) followed by 2 h reperfusion. Cardiac infarction was determined by 2,3,5-triphenyltetrazolium chloride triazole (TTC) staining. Cardiac function was examined by echocardiography. Cardiac markers and oxidative stress factors were evaluated by ELISA. Autophagy-associated factors were detected by western blot. Relationship between miR-542-3p and ADAM9 was tested by dual-luciferase reporter gene assay, RT-qPCR, and western blot. Sev treatment ameliorated cardiac dysfunction, myocardial oxidative stress, and histopathological damages, decreased myocardial infarction size and myocardial apoptotic cells after myocardial I/R injury. Sev treatment elevated miR-542-3p expression and decreased ADAM9 expression in myocardial tissues after myocardial I/R injury. miR-542-3p overexpression could enhance the ameliorative effects of Sev on myocardial injury and myocardial autophagy in I/R mice. miR-542-3p targeted and negatively regulated ADAM9 expression. ADAM9 overexpression reversed the ameliorative effects of miR-542-3p up-regulation on myocardial injury and myocardial autophagy in Sev-treated I/R mice. Sev treatment could ameliorate myocardial injury and myocardial autophagy in I/R mice, mediated by mechanisms that include miR-542-3p up-regulation and ADAM9 down-regulation. [ABSTRACT FROM AUTHOR]

The article "Highlights from the Circulation Family of Journals" covers various topics such as the association of C-reactive protein with incident heart failure, the impact of telehealth coverage on hypertension management, the association of circulating PCSK9 with myocardial ischemia, the incidence of failure to rescue after percutaneous coronary intervention complications, the study of contact force in pulsed field ablation, and the addition of a metabolomics risk score for coronary heart disease. The research presented in the article focuses on diverse populations and provides valuable insights into cardiovascular health. [Extracted from the article]

Introduction: Eleclazine is a highly selective late sodium current inhibitor, possibly effective in reducing ventricular fibrillation (VF) in heart failure (HF) with ischemia-reperfusion (IR) injury. The electrophysiological effects of eleclazine at therapeutic hypothermia (TH) are unknown. We investigated the effects of eleclazine in suppressing VF in failing rabbit hearts with IR injury undergoing TH. Method: HF was induced by right ventricular pacing. An IR model was created using coronary artery ligation for 60 min, followed by reperfusion for 30 min. Hearts were excised and Langendorff-perfused for optical mapping and electrophysiological studies. Electrophysiological studies were repeated after TH (33°C) for 30 min or eleclazine (1 μm) infusion for 20 min. Results: In failing IR-injured hearts, eleclazine reduced action potential duration (APD) dispersion and accelerated intracellular Ca2+ uptake to suppress arrhythmogenic alternans but also exacerbated rate-dependent conduction slowing, resulting in neutral effects on VF inducibility at normothermia. TH increased VF severity. Eleclazine after TH ameliorated TH-induced APD dispersion and further depressed conduction to reduce VF inducibility and severity. TH after eleclazine also slowed conduction to a greater extent to reduce VF inducibility and severity by extrastimulus pacing. In control IR-injured hearts, eleclazine increased VF severity by dynamic pacing at normothermia, which was counteracted by TH. Conclusions: Eleclazine does not prevent VF at normothermia but reduces VF inducibility and severity by extrastimulus pacing at TH in isolated failing hearts with regional IR injury. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the role and underlying mechanisms of Peroxisome proliferator-activated receptor gamma (PPARγ) and its m6A methylation in renal ischemia-reperfusion (I/R) injury and ferroptosis of tubular epithelial cells (TECs). High-throughput transcriptome sequencing was performed on renal tissue samples from I/R injury models and sham-operated mice, complemented by in vivo and in vitro experiments focusing on the PPARγ activator Rosiglitazone and the manipulation of METTL14 and IGF2BP2 expression. Key evaluations included renal injury assessment, ferroptosis indicator measurement, and m6A methylation analysis of PPARγ. Our findings highlight the critical role of the PPARγ pathway and ferroptosis in renal I/R injury, with Rosiglitazone ameliorating renal damage and TEC ferroptosis. METTL14-mediated m6A methylation of PPARγ, dependent on IGF2BP2, emerged as a pivotal regulator of PPARγ expression, renal injury, and ferroptosis. This study reveals that PPARγ m6A methylation, orchestrated by METTL14 through an IGF2BP2-dependent mechanism, plays a crucial role in mitigating renal I/R injury and TEC ferroptosis. These insights offer promising avenues for therapeutic strategies targeting acute kidney injury. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to test different anesthetic mixtures in order to identify the most suitable one for a surgical cardiac ischemia-reperfusion model in mice. Methods: 1) Sixty four mice were submitted to one of the 6 combinations of ketamine or alfaxalone associated to xylazine, medetomidine or midazolam. Depth and quality of anesthesia were evaluated via 5 reflex scores. 2) Impact of analgesic (buprenorphine or butorphanol), anesthesia reversal (with atipamezole) and surgery (cardiac ischemia-reperfusion surgery) have been tested in the selected protocols. 3) infarction size has been measured with TTC (Triphenyl Tetrazolium Chloride) method in mice anesthetized with best protocols. Results: Protocol involving medetomidine induced the longest surgical anesthesia: (median = 120, {interquartile range = 100–125}) min with ketamine and 53 {25–100} min with alfaxalone. Butorphanol substitution with buprenorphine did not alter time-related anesthesia parameters. Atipamezole reversal considerably reduced both recovery and immobilization time (respectively 22 {18–30} min and 98 {88–99} min vs. 55 {40–70} min and 143 {131–149} min, in groups with no reversal, p = 0.001) with no impact on infarction size measurement. Conclusion: In this study, the combination alfaxalone/medetomidine/buprenorphine (80/0,3/0,075 mg.kg-1, s.c.) associated with reversal by atipamezole was a reliable anesthetic protocol for murine surgery, particularly for the study of ischemia-reperfusion. [ABSTRACT FROM AUTHOR]