Trends in pharmacological sciences最新文献

The psychedelic compound psilocybin has recently emerged as a therapeutic intervention for various mental health conditions. Psilocybin is a potent agonist of serotonin (5-HT) receptors (5-HTRs), which are expressed in the brain and throughout peripheral tissues, with particularly high expression in the gastrointestinal (GI) tract. However, no studies have investigated the possibility that peripheral actions of psilocybin may contribute to improvements in mental health outcomes. This is despite strong evidence for disturbed gut-brain signalling in conditions in which psilocybin is being tested clinically. In this Opinion, we highlight the likely actions of psychedelics in the gut and provide initial support for the premise that peripheral actions may be involved in rapid and long-term therapeutic effects. A greater understanding of all sites and modes of action will guide more targeted approaches to drug development.

Muscle contraction is orchestrated by the well-understood thin filaments and the markedly complex thick filaments. Studies by Dutta et al. and Tamborrini et al., discussed here, have unravelled the structure of the mammalian heart thick filament in exquisite near-atomic detail and pave the way for understanding physiological modulation pathways and mutation-induced dysfunction and for designing potential drugs to modify defects.

Olfactory receptors (ORs) form the most important chemosensory receptor family responsible for our sense of smell in the nasal olfactory epithelium. This receptor family belongs to the class A G protein-coupled receptors (GPCRs). Recent research has indicated that ORs are involved in many nonolfactory physiological processes in extranasal tissue, such as the brain, pancreas, and testes, and implies the possible role of their dysregulation in various diseases. The recently released structures of OR51E2 and consensus OR52 have also unveiled the uniqueness of ORs from other class A GPCR members. In this review, we discuss these recent developments and computational modeling efforts toward understanding the structural properties of unresolved ORs, which could guide potential future OR-targeted drug discovery.

B cell leukemia/lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics were reported to selectively kill senescent cells and improve age-related diseases. Defining why these cells show increased sensitivity to these molecules will help to identify new pharmacological compounds with senolytic activity. Here, we discuss how recent research findings provide new clues to understand this vulnerability.

Abnormal iron metabolism has long been regarded as a key metabolic hallmark of cancer. As a critical cofactor, iron contributes to tumor progression by participating in various processes such as mitochondrial electron transport, gene regulation, and DNA synthesis or repair. Although the role of iron in tumor cells has been widely studied, recent studies have uncovered the interplay of iron metabolism between tumor cells and immune cells, which may affect both innate and adaptive immune responses. In this review, we discuss the current understanding of the regulatory networks of iron metabolism between cancer cells and immune cells and how they contribute to antitumor immunity, and we analyze potential therapeutics targeting iron metabolism. Also, we highlight several key challenges and describe potential therapeutic approaches for future investigations.

Persistent inflammation in damaged joints results in metabolic dysregulation of the synovial microenvironment, causing pathogenic alteration of cell activity in rheumatoid arthritis (RA). Recently, the role of metabolite and metabolite-sensing G protein-coupled receptors (GPCRs) in the RA-related inflammatory immune response (IIR) has become a focus of research attention. These GPCRs participate in the progression of RA by modulating immune cell activation, migration, and inflammatory responses. Here, we discuss recent evidence implicating metabolic dysregulation in RA pathogenesis, focusing on the connection between RA-related IIR and GPCR signals originating from the synovial joint and gut. Furthermore, we discuss future directions for targeting metabolite-sensing GPCRs for therapeutic benefit, emphasizing the importance of identifying endogenous ligands and investigating the various transduction mechanisms involved.

Networking is an important skill for finding social relationships relevant to one's career. However, networking can be difficult to navigate as different social situations and career levels require unique skill sets. Here, we provide tips for effective networking at conferences, dinners, and other events.