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Luteolin, a flavonoid present in botanical drugs, plants, and dietary sources, has demonstrated anticancer properties against various tumors, yet its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to uncover the molecular mechanism of luteolin in DLBCL treatment using a combination of in vitro and in vivo experiments and computational analysis. Human DLBCL cell lines U2932 and OCI-LY10 were utilized to assess luteolin’s impact on cell growth, apoptosis, cell cycle progression, and the modulation of JAK2/STAT3 pathway proteins. In vivo, a U2932 tumor-bearing nude mice model was employed to evaluate luteolin’s antitumor efficacy and its effects on JAK2/STAT3 pathway protein expression. Additionally, molecular dynamics simulations were conducted to explore the interaction between luteolin and JAK2. The findings revealed that luteolin significantly suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase in both cell lines. In the mouse model, luteolin effectively inhibited tumor growth and downregulated the expression of phosphorylated JAK2 and STAT3 without altering the total protein levels of JAK2 and STAT3. Computational analysis indicated stable binding of luteolin to JAK2. Collectively, these results suggest that luteolin’s anti-DLBCL activity may be mediated through the regulation of the JAK2/STAT3 signaling pathway, positioning it as a potential therapeutic agent for DLBCL.

Abstract Janus Kinases (JAKs) play a crucial role as therapeutic targets for various cancers. However, the current JAK inhibitors (JAKi) available have limited therapeutic benefits due to their lack of selectivity. This review focuses on the structural analysis to elucidate the molecular determinants of JAKs specificity and the discovery and design of selective JAKi. It includes descriptions and comparison of different JAK structures and their binding sites, a comparative analysis of JAKi and their binding modes, detailed interaction fingerprints (IFPs), and an extensive structure‐selectivity relationship (SSRs). Moreover, the review also explores the challenges and possibilities of using computational structure‐based methods for discovering and designing selective JAKi. Other structure‐based approaches, such as targeting the pseudokinase domain, as well as covalent and allosteric designs, are also covered. Based on this analysis, key determinants corresponding to JAK specificity and rational medicinal chemistry strategies are proposed to facilitate the development of highly selective JAKi. Overall, we aim to enhance the understanding of JAK specificity and explore strategies that can lead to the discovery of effective and selective JAKi in cancer therapy, thus improving the prognosis for cancer patients.

The dynamic balance of cardiomyocytes and neurons is essential to maintain the normal physiological functions of heart and brain. If excessive cells die in tissues, serious Cardio-Cerebrovascular Diseases would occur, namely, hypertension, myocardial infarction, and ischemic stroke. The regulation of cell death plays a role in promoting or alleviating Cardio-Cerebrovascular Diseases. Ferroptosis is an iron-dependent new type of cell death that has been proved to occur in a variety of diseases. In our review, we focus on the critical role of ferroptosis and its regulatory mechanisms involved in Cardio-Cerebrovascular Diseases, and discuss the important function of ferroptosis-related inhibitors in order to propose potential implications for the prevention and treatment of Cardio-Cerebrovascular Diseases.

Cardio-Cerebrovascular Disease is a collective term for cardiovascular disease and cerebrovascular disease, being a serious threat to human health. A growing number of studies have proved that the content of inflammatory factors or mediators determines the stability of vascular plaque and the incidence of cardio-cerebrovascular event, and involves in the process of Cardio-Cerebrovascular Diseases. Interleukin-6 is a widely used cytokine that causes inflammation and oxidative stress, which would further result in cardiac and cerebral injury. The increased expression of interleukin-6 is closely related to atherosclerosis, myocardial infarction, heart failure and ischemic stroke. It is a key risk factor for these diseases by triggering inflammatory reaction and inducing other molecules release. Therefore, interleukin-6 may become a potential target for Cardio-Cerebrovascular Diseases in the future. This paper is aimed to discuss the expression changes and pathological mechanisms of interleukin-6 in Cardio-Cerebrovascular Diseases, and to provide a novel strategy for the prevention and treatment of Cardio-Cerebrovascular Diseases.