Objective: Research suggests that Puerarin may protect against sepsis-induced myocardial damage. However, the mechanisms responsible for Puerarin’s cardioprotective effect remain largely unclear. In this study, our objective is to investigate the role of Puerarin-induced AMPK-mediated ferroptosis signaling in protecting myocardial injury. Methods: 48 male Sprague-Dawley rats were randomly divided into four groups: control group, LPS group, LPS + Pue group, LPS + Pue + Era (Erastin, ferroptosis activator) group, or LPS + Pue + CC (compound C, AMPK inhibitor) group. During the experiment, cardiac systolic function indexes and myocardial histopathological changes were monitored. The serum levels of myocardial injury marker enzyme, inflammatory response related marker enzyme, and oxidative stress related-marker enzyme were measured with ELISA. Apoptotic cardiomyocytes, the iron content in myocardial tissue, apoptosis-related proteins, AMPK, and ferroptosis-related proteins were determined. Results: Puerarin inhibited the myocardial injury induced by LPS. The cardioprotective effects of Puerarin decreased after adding ferroptosis-activating compound Erastin. The protein expression levels of GPX4 and ferritin were down-regulated, whereas ACSL4, TFR, and heart iron content were up-regulated in LPS + Pue + Era group compared with LPS+Pue group. A significant difference was identified between LPS + Pue + Era group and LPS + Pue group in P-AMPK and T-AMPK levels. Meanwhile, after providing CC, P-AMPK/T-AMPK was significantly reduced, the protein expression levels of GPX4 and ferritin were down-regulated. ACSL4, TFR, and the heart iron content were up-regulated in LPS + Pue + CC group compared to LPS + Pue group. Conclusions: Puerarin protected against sepsis-induced myocardial injury, and AMPK-mediated ferroptosis signaling played a crucial role in its cardioprotective effect.

Myocardial ischemia-reperfusion injury (MIRI) results in the aggravation of myocardial injury caused by rapid recanalization of the ischemic myocardium. In the past few years, there is a growing interest in investigating the complex pathophysiological mechanism of MIRI for the identification of effective targets and drugs to alleviate MIRI. Currently, pyroptosis, a type of inflammatory programmed death, has received greater attention. It is involved in the MIRI development in combination with other mechanisms of MIRI, such as oxidative stress, calcium overload, necroptosis, and apoptosis, thereby forming an intertwined association between different pathways that affect MIRI by regulating common pathway molecules. This review describes the pyroptosis mechanism in MIRI and its relationship with other mechanisms, and also highlights non-coding RNAs and non-cardiomyocytes as regulators of cardiomyocyte pyroptosis by mediating associated pathways or proteins to participate in the initiation and development of MIRI. The research progress on novel small molecule drugs, clinical drugs, traditional Chinese medicine, etc. for regulating pyroptosis can play a crucial role in effective MIRI alleviation. When compared to research on other mature mechanisms, the research studies on pyroptosis in MIRI are inadequate. Although many related protective drugs have been identified, these drugs generally lack clinical applications. It is necessary to further explore and verify these drugs to expand their applications in clinical setting. Early inhibition of MIRI by targeted regulation of pyroptosis is a key concern that needs to be addressed in future studies.

Inhalation anesthetics have been demonstrated to have protective effects against myocardial ischemia reperfusion injury (MIRI). O-linked GlcNAcylation (O-GlcNAc) modifications have been shown to protect against MIRI. This study aimed to investigate whether O-GlcNAcylation and necroptosis signaling were important for sevoflurane postconditioning (SPC) induced cardioprotective effects. Apart from rats in the SHAM and sevoflurane (SEVO) group, rats underwent 30 min ischemia followed by 2 h reperfusion. Cardiac hemodynamics and function were determined. In addition, myocardial infarction size, cardiac function parameters, myocardial lactic dehydrogenase (LDH) content, myocardium histopathological changes, necrotic myocardium, O-GlcNAcylation, and protein expression levels of necroptosis biomarkers were measured, together with co-immunoprecipitation experiments using proteins associated with the necroptosis pathway and O-GlcNAcylation. SPC reduced myocardial infarction size, ameliorated cardiac function, restored hemodynamic performance, improved histopathological changes, and reduced receptor-interacting protein kinase 1 (RIPK1)/receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like (MLKL) mediated necroptosis. In addition, SPC up-regulated O-GlcNAc transferase (OGT) mediated O-GlcNAcylation, increased O-GlcNAcylated RIPK3, and inhibited the association of RIPK3 and MLKL. However, OSMI-1, an OGT inhibitor, abolished SPC mediated cardioprotective effects and inhibited OGT mediated up-regulation of O-GlcNAcylation and down-regulation of RIPK3 and MLKL proteins induced by SPC. Our study demonstrated that SPC restrained MIRI induced necroptosis via regulating OGT mediated O-GlcNAcylation of RIPK3 and lessening the formulation of RIPK3/MLKL complex.

Local anesthetics are widely used clinically for perioperative analgesia to achieve comfort in medical treatment. However, when the concentration of local anesthetics in the blood exceeds the tolerance of the body, local anesthetic systemic toxicity (LAST) will occur. With the development and popularization of positioning technology under direct ultrasound, the risks and cases of LAST associated with direct entry of the anesthetic into the blood vessel have been reduced. Clinical occurrence of LAST usually presents as a series of severe toxic reactions such as myocardial depression, which is life-threatening. In addition to basic life support (airway management, advanced cardiac life support, etc.), intravenous lipid emulsion (ILE) has been introduced as a treatment option in recent years and has gradually become the first-line treatment for LAST. This review introduces the mechanisms of LAST and identifies the clinical symptoms displayed by the central nervous system and cardiovascular system. The paper features the multimodal mechanism of LAST reversal by ILE, describes research progress in the field, and identifies other anesthetics involved in the resuscitation process of LAST. Finally, the review presents key issues in lipid therapy. Although ILE has achieved notable success in the treatment of LAST, adverse reactions and contraindications also exist; therefore, ILE requires a high degree of attention during use. More in-depth research on the treatment mechanism of ILE, the resuscitation dosage and method of ILE, and the combined use with other resuscitation measures is needed to improve the efficacy and safety of clinical resuscitation after LAST in the future.

With the increasing incidence of metabolic diseases year by year and their impact on the incidence of cardiovascular diseases, metabolic diseases have attracted great attention as a major health care problem, but there is still no effective treatment. Oxidative stress and inflammation are the main mechanisms leading to metabolic diseases. T cells are involved in the inflammatory response, which can also regulate the development of metabolic diseases, CD4+ T cells and CD8+ T cells are mainly responsible for the role. Th1 and Th17 differentiated from CD4+ T promote inflammation, while Th2 and Treg inhibit inflammation. CD8+ T cells also contribute to inflammation. The severity and duration of inflammatory reactions can also lead to different degrees of progression of metabolic diseases. Moreover, mTOR, PI3K-Akt, and AMPK signaling pathways play unique roles in the regulation of T cells, which provide a new direction for the treatment of metabolic diseases in the future. In this review, we will elaborate on the role of T cells in regulating inflammation in various metabolic diseases, the signaling pathways that regulate T cells in metabolic diseases, and the latest research progress.

Therapeutic hypothermia (TH) may attenuate myocardial ischaemia–reperfusion injury, thereby improving outcomes in acute myocardial infarction. However, the specific mechanism by which TH alleviates MIRI has not been elucidated so far. In this study, 120 healthy male Sprague‐Dawley rats were randomly divided into five groups. Haemodynamic parameters, myocardial infarction area, histological changes and the levels of cardiac enzymes, caspase‐1 and inflammatory cytokines were determined. In addition, the extent of myocardial fibrosis, the degree of cardiomyocyte apoptosis and the expression levels of SIRT3, GSDMD‐N, fibrosis‐related proteins and inflammation‐related proteins were estimated.TH reduced myocardial infarct area and cardiac enzyme levels, improved cardiomyopathic damage and haemodynamic indexes, and attenuated myocardial fibrosis, the protein expression levels of collagen I and III, myocardial apoptosis, the levels of inflammatory cytokines and inflammation‐related proteins. Notably, the immunofluorescence and protein expression levels of SIRT3 were upregulated in the 34H+DMSO group compared to the I/R group, but this protective effect was abolished by the SIRT3 inhibitor 3‐TYP. After administration of Mcc950, the reversal effects of 3‐TYP were significantly abolished, and TH could protect against MIRI in a rat isolated heart model by inhibiting inflammation and fibrosis. The SIRT3/NLRP3 signalling pathway is one of the most important signalling pathways in this regard.