Neutrophil extracellular traps in central nervous system (CNS) diseases.

Excessive induction of inflammatory and immune responses is widely considered as one of vital factors contributing to the pathogenesis and progression of central nervous system (CNS) diseases. Neutrophils are well-studied members of inflammatory and immune cell family, contributing to the innate and adaptive immunity. Neutrophil-released neutrophil extracellular traps (NETs) play an important role in the regulation of various kinds of diseases, including CNS diseases. In this review, current knowledge on the biological features of NETs will be introduced. In addition, the role of NETs in several popular and well-studied CNS diseases including cerebral stroke, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and neurological cancers will be described and discussed through the reviewing of previous related studies.

T cells, NK cells, and tumor-associated macrophages in cancer immunotherapy and the current state of the art of drug delivery systems.

The immune system provides full protection for the body by specifically identifying 'self' and removing 'others'; thus protecting the body from diseases. The immune system includes innate immunity and adaptive immunity, which jointly coordinate the antitumor immune response. T cells, natural killer (NK) cells and tumor-associated macrophages (TAMs) are the main tumor-killing immune cells active in three antitumor immune cycle. Cancer immunotherapy focusses on activating and strengthening immune response or eliminating suppression from tumor cells in each step of the cancer-immunity cycle; thus, it strengthens the body's immunity against tumors. In this review, the antitumor immune cycles of T cells, natural killer (NK) cells and tumor-associated macrophages (TAMs) are discussed. Co-stimulatory and co-inhibitory molecules in the three activity cycles and the development of drugs and delivery systems targeting these molecules are emphasized, and the current state of the art of drug delivery systems for cancer immunotherapy are summarized.

NLRP3 Inflammasome in Atherosclerosis: Putting Out the Fire of Inflammation.

Atherosclerosis (AS) is a chronic inflammatory disease with thickening or hardening of the arteries, which led to the built-up of plaques in the inner lining of an artery. Among all the clarified pathogenesis, the over-activation of inflammatory reaction is one of the most acknowledged one. The nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3 (NLRP3) inflammasome, as a vital and special form of inflammation and innate immunity, has been widely revealed to participate in the onset and development of AS. This review will introduce the process of the pathogenesis and progression of AS, and will describe the biological features of the NLRP3 inflammasome. Furthermore, the role of the NLRP3 inflammasome in AS and the possible mechanisms will be discussed. In addition, several kinds of agents with the effect of anti-atherosclerotic taking advantage of the NLRP3 inflammasome intervention will be described and discussed in detail, including natural compounds (baicalin, dihydromyricetin, luteolin, 5-deoxy-rutaecarpine (R3) and Salvianolic acid A, etc.), microRNAs (microRNA-30c-5p, microRNA-9, microRNA-146a-5p, microRNA-16-5p and microRNA-181a, etc.), and autophagy regulators (melatonin, dietary PUFA and arglabin, etc.). We aim to provide novel insights in the exploration of the specific mechanisms of AS and the development of new treatments of AS.

ING5 inhibits lung cancer invasion and epithelial-mesenchymal transition by inhibiting the WNT/ß-catenin pathway.

BACKGROUND: ING5 is the last member of the Inhibitor of Growth (ING) candidate tumor suppressor family that has been implicated in multiple cellular functions, including cell cycle regulation, apoptosis, and chromatin remodeling. Our previous study showed that ING5 overexpression inhibits lung cancer aggressiveness and epithelial-mesenchymal transition (EMT), with unknown mechanisms. METHODS: Western blotting was used to detect total and phosphorylated levels of ß-catenin and EMT-related proteins. Immunofluorescent staining was used to observe E-cadherin expression. Proliferation and colony formation, wound healing, and Transwell migration and invasion assays were performed to study the proliferative and invasive abilities of cancer cells. RESULTS: ING5 overexpression promotes phosphorylation of ß-catenin at Ser33/37, leading to a decreased ß-catenin protein level. Small hairpin RNA-mediated ING5 knockdown significantly increased the ß-catenin level and inhibited phosphorylation of ß-catenin S33/37. Treatment with the WNT/ß-catenin inhibitor XAV939 inhibited ING5-knockdown promoted proliferation, colony formation, migration, and invasion of lung cancer A549 cells, with increased phosphorylation of ß-catenin S33/37 and a decreased ß-catenin level. XAV939 also impaired ING5-knockdown-induced EMT, as indicated by upregulated expression of the EMT marker E-cadherin, an epithelial marker; and decreased expression of N-cadherin, a mesenchymal marker, and EMT-related transcription factors, including Snail, Slug, Twist, and Smad3. Furthermore, XAV939 could inhibit the activation of both IL-6/STAT3 and PI3K/Akt signaling pathways. CONCLUSION: ING5 inhibits lung cancer invasion and EMT by inhibiting the WNT/ß-catenin pathway.