Copper is a vital mineral, and an optimal amount of copper is required to support normal physiologic processes in various systems, including the cardiovascular system. Over the past few decades, copper-induced cell death, named cuproptosis, has become increasingly recognized as an important process mediating the pathogenesis and progression of cardiovascular disease (CVD), including atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure. Therefore, an in-depth understanding of the regulatory mechanisms of cuproptosis in CVD may be useful for improving CVD management. Here, we review the relationship between copper homeostasis and cuproptosis-related pathways in CVD, as well as therapeutic strategies addressing copper-induced cell death in CVD.

Ischemia/reperfusion (I/R) injury is a life-threatening vascular emergency following myocardial infarction. Our previous study showed cardioprotective effects of metformin against myocardial I/R injury. In this study, we further examined the involvement of AMPK mediated activation of NLRP3 inflammasome in this cardioprotective effect of metformin. Myocardial I/R injury was simulated in a rat heart Langendorff model and neonatal rat ventricle myocytes (NRVMs) were subjected to hypoxi/reoxygenation (H/R) to establish an in vitro model. Outcome measures included myocardial infarct size, hemodynamic monitoring, myocardial tissue injury, myocardial apoptotic index and the inflammatory response. myocardial infarct size and cardiac enzyme activities. First, we found that metformin postconditioning can not only significantly alleviated myocardial infarct size, attenuated cell apoptosis, and inhibited myocardial fibrosis. Furthermore, metformin activated phosphorylated AMPK, decreased pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β, and decreased NLRP3 inflammasome activation. In isolated NRVMs metformin increased cellular viability, decreased LDH activity and inhibited cellular apoptosis and inflammation. Importantly, inhibition of AMPK phosphorylation by Compound C (CC) resulted in decreased survival of cardiomyocytes mainly by inducing the release of inflammatory cytokines and increasing NLRP3 inflammasome activation. Finally, in vitro studies revealed that the NLRP3 activator nigericin abolished the anti-inflammatory effects of metformin in NRVMs, but it had little effect on AMPK phosphorylation. Collectively, our study confirmed that metformin exerts cardioprotective effects by regulating myocardial I/R injury-induced inflammatory response, which was largely dependent on the enhancement of the AMPK pathway, thereby suppressing NLRP3 inflammasome activation.

With long-term metabolic malfunction, diabetes can cause serious damage to whole-body tissue and organs, resulting in a variety of complications. Therefore, it is particularly important to further explore the pathogenesis of diabetes complications and develop drugs for prevention and treatment. In recent years, different from apoptosis and necrosis, ferroptosis has been recognized as a new regulatory mode of cell death and involves the regulation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Evidence shows that ferroptosis and ferritinophagy play a significant role in the occurrence and development of diabetes complications. we systematically review the current understanding of ferroptosis and ferritinophagy, focusing on their potential mechanisms, connection, and regulation, discuss their involvement in diabetes complications, and consider emerging therapeutic opportunities and the associated challenges with future prospects. In summary, ferroptosis and ferritinophagy are worthy targets for the treatment of diabetes complications, but their complete molecular mechanism and pathophysiological process still require further study.

Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aβ deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.

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.

ChatGPT, an artificial intelligence (AI) system powered by large-scale language models, has garnered significant interest in healthcare. Its performance dependent on the quality and quantity of training data available for a specific language, with the majority of it being in English. Therefore, its effectiveness in processing the Chinese language, which has fewer data available, warrants further investigation. This study aims to assess the of ChatGPT’s ability in medical education and clinical decision-making within the Chinese context. We utilized a dataset from the Chinese National Medical Licensing Examination (NMLE) to assess ChatGPT-4’s proficiency in medical knowledge in Chinese. Performance indicators, including score, accuracy, and concordance (confirmation of answers through explanation), were employed to evaluate ChatGPT’s effectiveness in both original and encoded medical questions. Additionally, we translated the original Chinese questions into English to explore potential avenues for improvement. ChatGPT scored 442/600 for original questions in Chinese, surpassing the passing threshold of 360/600. However, ChatGPT demonstrated reduced accuracy in addressing open-ended questions, with an overall accuracy rate of 47.7%. Despite this, ChatGPT displayed commendable consistency, achieving a 75% concordance rate across all case analysis questions. Moreover, translating Chinese case analysis questions into English yielded only marginal improvements in ChatGPT’s performance (p = 0.728). ChatGPT exhibits remarkable precision and reliability when handling the NMLE in Chinese. Translation of NMLE questions from Chinese to English does not yield an improvement in ChatGPT’s performance.