The Role of P53 in Myocardial Ischemia-Reperfusion Injury.

PURPOSE: P53 is one of the key tumor suppressors. In normal cells, p53 is maintained at low levels by the ubiquitination of the ubiquitinated ligase MDM2. In contrast, under stress conditions such as DNA damage and ischemia, the interaction between p53 and MDM2 is blocked and activated by phosphorylation and acetylation, thereby mediating the trans-activation of p53 through its target genes to regulate a variety of cellular responses. Previous studies have shown that the expression of p53 is negligible in normal myocardium, tends to increase in myocardial ischemia and is maximally induced in ischemia-reperfused myocardium, demonstrating a possible key role of p53 in the development of MIRI. In this review, we detail and summarize recent studies on the mechanism of action of p53 in MIRI and describe the therapeutic agents targeting the relevant targets to provide new strategies for the prevention and treatment of MIRI. METHODS: We collected 161 relevant papers mainly from Pubmed and Web of Science (search terms "p53" and "myocardial ischemia-reperfusion injury"). After that, we selected pathway studies related to p53 and classified them according to their contents. We eventually analyzed and summarized them. RESULTS AND CONCLUSION: In this review, we detail and summarize recent studies on the mechanism of action of p53 in MIRI and validate its status as an important intermediate affecting MIRI. On the one hand, p53 is regulated and modified by multiple factors, especially non-coding RNAs; on the other hand, p53 regulates apoptosis, programmed necrosis, autophagy, iron death and oxidative stress in MIRI through multiple pathways. More importantly, several studies have reported medications targeting p53-related therapeutic targets. These medications are expected to be effective options for the alleviation of MIRI, but further safety and clinical studies are needed to convert them into clinical applications.

The impact of early pregnancy metabolic disorders on pregnancy outcome and the specific mechanism.

Miscarriage is the most common complication of pregnancy. The most common causes of early miscarriage are chromosomal abnormalities of the embryo, maternal endocrine abnormalities, organ malformations, and abnormal immune factors. Late miscarriages are mostly caused by factors such as cervical insufficiency. However, the causes of 50% of miscarriages remain unknown. Recently, increasing attention has been given to the role of metabolic abnormalities in miscarriage. In this review, we mainly discuss the roles of four major metabolic pathways (glucose, lipid, and amino acid metabolism, and oxidation‒reduction balance) in miscarriage and the metabolism-related genes that lead to metabolic disorders in miscarriage. Depending on aetiology, the current treatments for miscarriage include hormonal and immunological drugs, as well as surgery, while there are few therapies for metabolism. Therefore, we also summarize the drugs for metabolism-related targets. The study of altered metabolism underlying miscarriage not only helps us to understand the mechanisms involved in miscarriage but also provides an important basis for clinical research on new therapies.