International journal of drug discovery and pharmacology最新文献

The Rho/ROCK (Rho-associated coiled-coil-containing protein kinase) signaling pathway plays a pivotal role in regulating diverse cellular processes, including cytoskeletal organization, cell migration, proliferation, and apoptosis. Dysregulation of this pathway has been implicated in the pathogenesis of various diseases, such as cardiovascular disorders, cancer, neurological conditions, and fibrotic diseases. Accumulating evidence supports the therapeutic potential of targeting Rho/ROCK, with several inhibitors currently under investigation or in clinical use. This review summarizes the molecular mechanisms underlying Rho/ROCK signaling, explores its involvement in disease progression, and discusses recent advances in the development of and the clinical application of ROCK inhibitors as promising therapeutic agents.

Although previous reviews explored the roles of selected immune checkpoints (ICPs) in cardiovascular diseases (CVD) and cerebrovascular diseases from various perspectives, many related aspects have yet to be thoroughly reviewed and analyzed. Our comprehensive review addresses this gap by discussing the cellular functions of ICPs, focusing on the tissue-specific and microenvironment-localized transcriptomic and posttranslational regulation of ICP expressions, as well as their functional interactions with metabolic reprogramming. We also analyze how 14 pairs of ICPs, including CTLA-4/CD86-CD80, PD1-PDL-1, and TIGIT-CD155, regulate CVD pathogenesis. Additionally, the review covers the roles of ICPs in modulating CD4⁺Foxp3⁺ regulatory T cells (Tregs), T cells, and innate immune cells in various CVDs and cerebrovascular diseases. Furthermore, we outline seven immunological principles to guide the development of new ICP-based therapies for CVDs. This timely and thorough analysis of recent advancements and challenges provide new insights into the role of ICPs in CVDs, cerebrovascular diseases and Tregs, and will support the development of novel therapeutics strategies for these diseases.

Cardiomyocytes are highly dependent on oxygen for optimal function. Disruption of oxygen availability, as in the case of ischemic heart disease, can significantly impair heart function. Moreover, comorbidities like diabetes, hyperlipidemia, and hypertension can exacerbate ischemic cardiac injury. However, cardiomyocytes possess inherent protective mechanisms that can be activated to enhance myocardial survival under such conditions. Understanding the functions and regulatory mechanisms of these cardioprotective genes is crucial for advancing our knowledge of cardiovascular health and for developing therapeutic strategies. This review examines the intricate mechanisms of cardioprotection, with a focus on key genes and proteins, including hypoxia-inducible factor-1 (HIF-1), heme oxygenase-1 (HO-1), glucose transporter 1 (GLUT-1), and GLUT-4. In addition, the review explores the roles and regulation of these factors in the heart under ischemic stress, shedding light on their relevance in conditions like diabetes, hypertension, and hyperlipidemia/atherosclerosis. Moreover, it highlights the complex interplay among their mechanisms and suggests opportunities for developing targeted therapiesfor the treatment of ischemic heart disease, hypertension, and hyperlipidemia.

Integrins are transmembrane receptors that, as critical participants in a vast range of pathological processes, are potential therapeutic targets. However, in only a few cases has the promise been realized by drug approval. In this review, we briefly review basic integrin biology and participation in disease, challenges in the development of safe, effective integrin-targeted therapies, and recent advances that may lead to progress.