The innate immune system is the first line of host defense against infection and involves several different cell types. Here we investigated the role of the phosphatidylinositol 3 kinase (PI3K) signaling pathway in innate immune cells. By blocking this pathway with pharmacological inhibitors, we found that the production of proinflammatory cytokines was drastically suppressed in monocytes and macrophages. Further study revealed that the suppression was mainly related to the mammalian target of rapamycin (mTOR)/p70S6K signaling. In addition, we found that the PI3K pathway was involved in macrophage motility and neovascularization. Our data provide a rationale that inhibition of the PI3K signaling pathway could be an attractive approach for the management of inflammatory disorders.

The synaptonemal complex (SC) is an ordered but highly dynamic structure assembled between homologous chromosomes to control interhomologous crossover formation, ensuring accurate meiotic chromosome segregation. However, the mechanisms regulating SC assembly and dynamics remain unclear. Here, we identified two new SC components, SYP-5 and SYP-6, in Caenorhabditis elegans that have distinct expression patterns and form distinct SC assembly units with other SYPs through stable interactions. SYP-5 and SYP-6 exhibit diverse in vivo SC regulatory functions and distinct phase separation properties in cells. Charge-interacting elements (CIEs) are enriched in SC intrinsically disordered regions (IDRs), and IDR deletion or CIE removal confirmed a requirement for these elements in SC regulation. Our data support the theory that multivalent weak interactions between the SC units drive SC formation and that CIEs confer multivalency to the assembly units.

Mucociliary epithelium lining the upper and lower respiratory tract constitutes the first line of defense of the airway and lungs against inhaled pollutants and pathogens. The concerted beating of multiciliated cells drives mucociliary clearance. Abnormalities in both the structure and function of airway cilia have been implicated in obstructive lung diseases. Emerging evidence reveals a close correlation between lung diseases and environmental stimuli such as sulfur dioxide and tobacco particles. However, the underlying mechanism remains to be described. In this review, we emphasize the importance of airway cilia in mucociliary clearance and discuss how environmental pollutants affect the structure and function of airway cilia, thus shedding light on the function of airway cilia in preventing obstructive lung diseases and revealing the negative effects of environmental pollutants on human health.

Angiogenesis, a process by which the preexisting blood vasculature gives rise to new capillary vessels, is associated with a variety of physiologic and pathologic conditions. However, the molecular mechanism underlying this important process remains poorly understood. Here we show that histone deacetylase 6 (HDAC6), a microtubule-associated enzyme critical for cell motility, contributes to angiogenesis by regulating the polarization and migration of vascular endothelial cells. Inhibition of HDAC6 activity impairs the formation of new blood vessels in chick embryos and in angioreactors implanted in mice. The requirement for HDAC6 in angiogenesis is corroborated in vitro by analysis of endothelial tube formation and capillary sprouting. Our data further show that HDAC6 stimulates membrane ruffling at the leading edge to promote cell polarization. In addition, microtubule end binding protein 1 (EB1) is important for HDAC6 to exert its activity towards the migration of endothelial cells and generation of capillary-like structures. These results thus identify HDAC6 as a novel player in the angiogenic process and offer novel insights into the molecular mechanism governing endothelial cell migration and angiogenesis.

The microtubule cytoskeleton plays a critical role in a wide range of cellular activities and has been shown to be a highly effective target for the treatment of human malignancies. Despite the recent focus on proteomics and high-throughput profiling, it is clear that analysis of plant extracts has yielded several highly efficacious microtubule-targeting agents (MTAs) currently in clinical use, as well as agents in the current pipeline with promising efficacy. To date, a large proportion of the world’s plant biodiversity remains untapped by the pharmaceutical industry, presenting a major opportunity for the discovery of novel pharmacologically active lead compounds. Because plants contain an astonishing array of structurally diverse molecules, they represent an ideal source for the discovery of novel MTA leads. To demonstrate the importance of searching for novel bioactive compounds across the plant kingdom, herein, we summarize the discovery and development of plant-derived MTAs and discuss the challenges associated with searching for novel bioactive compounds from plants. We propose potential solutions to these problems with the aim of facilitating further exploration and identification of novel MTAs from plant biodiversity.