No abstract

The retinal pigment epithelium is a fundamental component of the retina that plays essential roles in visual functions. Damage to the structure and function of the retinal pigment epithelium leads to a variety of retinopathies, and there is currently no curative therapy for these disorders. Therefore, studying the relationship between the development, function, and pathobiology of the retinal pigment epithelium is important for the prevention and treatment of retinopathies. Here we review the function of the retinal pigment epithelium and its relevance to the pathobiology, and discuss potential strategies for the treatment of retinopathies. In doing so, we provide new viewpoints outlining new ideas for the future study and treatment of retinopathies.

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.

Orientation and positioning of the mitotic spindle are involved in dictating cell division axis and cleavage site, and play important roles in cell fate determination and tissue morphogenesis. However, how spindle movement is controlled to achieve a defined alignment within the dividing cell is not fully understood. Here, we describe an unexpected role for apoptosis signal-regulating kinase 1 (ASK1) in regulating spindle behavior. We find that ASK1 is required for proper mitotic progression and daughter cell adhesion to the substratum. ASK1 interacts with end-binding protein 1 (EB1) and phosphorylates EB1 at serine 40, threonine 154 and threonine 206, enhancing its binding to the plus ends of astral microtubules. Consequently, astral microtubules are stabilized and therefore capable of mediating spindle interaction with the cell cortex, a requirement for spindle movement. These findings reveal a previously undiscovered function of ASK1 in cell division by regulating spindle orientation and positioning, and point to the importance of protein phosphorylation in the regulation of spindle behavior.

Autophagy is a major cellular metabolic pathway that facilitates degradation of a subset of long-lived proteins and cytoplasmic organelles in eukaryotic cells. This pathway plays a vital role in preserving the cellular homeostasis of the cells themselves, in addition to maintaining the normal physiological state of cell renewal. Many stressors, such as starvation, ischaemia and oxidative stress can induce autophagy. In addition to its physiological roles, autophagy also occurs in a wide variety of pathological processes, including tumour progression, metabolic disorders, and neurodegenerative and lung diseases. In recent years, a growing body of evidence has shown that autophagy also plays a key role in the development of mammalian diseases, a function that has garnered substantial attention and study. An in-depth understanding of the molecular role that autophagy plays in pathological settings is vital for both the diagnosis and treatment of mammalian diseases and will aid in the search for novel targets for therapeutic drug intervention. Here, we provide an integrated review of recent studies implicating autophagy dysfunction in the progression of mammalian disorders and summarize research suggesting that the molecular pathways involved in autophagy could serve as potential therapeutic targets.

Scheme 1. Schematic of FGO@MN combined with mild PTT for refractory BBI elimination through an iron-actuated Janus therapy.

Highlights d HDAC6 upregulation drives connecting cilium disassembly in OIR mouse model of ROP d Oxygen changes activate ASK1 to phosphorylate HDAC6 in the OIR mouse retina d HDAC6 phosphorylation blocks its ubiquitination by VHL and proteasomal degradation d Inhibition of ASK1 or HDAC6 protects mice from oxygenchange-induced pathologies

The NOD-like receptors (NLRs) are cytosolic pattern-recognition receptors, which are critically involved in mucosal immune defense. The association of the NLR, NOD2, with inflammatory bowel disease first pointed to the NLRs potential function as guardians of the intestinal barrier. Since then, several studies have emphasized the importance of NLRs in maintaining gut homeostasis and intestinal infections, and in shaping the microbiota. In this review, we will highlight the function of NLRs in intestinal inflammation.