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Background Brain metastasis (BM) is associated with poor prognosis, recurrence, and death in patients with non-small cell lung cancer (NSCLC). Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been reported to be involved in the progression, metastasis and recurrence of malignancies. However, the potential role of LPCAT1 in NSCLC remains poorly understood. This study was aimed to identify genes involved in lung adenocarcinoma (LUAD) brain metastasis, and look into the role of LPCAT1 in LUAD progression. Methods We used integrative genomic analysis to identify genes involved in lung adenocarcinomas. LPCAT1 expression was evaluated in tumor tissues from LUAD patients and LUAD cell lines. The role of LPCAT1 was subsequently investigated both in vitro and in vivo. The mechanism underlying the involvement of LPCAT1 in LUAD progression was explored with the activator of PI3K/AKT pathway. RNA sequencing was performed to confirm the involvement of LPCAT1 and associated pathway in LUAD brain metastasis. Results LPCAT1 was up-regulated in LUAD tissues and cell lines. shRNA-mediated depletion of LPCAT1 not only abrogated cell proliferation, migration and invasion in vitro, but also arrested tumor growth and brain metastases in vivo. Notably, LPCAT1 at least partially influenced LUAD progression through PI3K/AKT signal pathway by targeting MYC transcription. Moreover, expression of LPCAT1 was higher in tissues of LUAD patients with BM than those without BM as revealed by IHC staining, RNA-Sequencing and qPCR analysis. Finally, elevated LPCAT1 expression in patients with lung adenocarcinomas was associated with a poor clinical outcome. Conclusions This study showed that LPCAT1 works as a regulator of cell metastasis and may serve as a novel therapeutic target for BM in lung adenocarcinoma. Electronic supplementary material The online version of this article (10.1186/s13046-019-1092-4) contains supplementary material, which is available to authorized users.

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Whether bone marrow modulates systemic metabolism remains unknown. Here, we found that (i) myeloid cell–specific myeloid-derived growth factor (MYDGF) deficiency exacerbated vascular inflammation, adhesion responses, endothelial injury, and atherosclerosis in vivo. (ii) Myeloid cell–specific MYDGF restoration attenuated vascular inflammation, adhesion responses and leukocyte homing and alleviated endothelial injury and atherosclerosis in vivo. (iii) MYDGF attenuated endothelial inflammation, apoptosis, permeability, and adhesion responses induced by palmitic acid in vitro. (iv) MYDGF alleviated endothelial injury and atherosclerosis through mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4)/nuclear factor κB (NF-κB) signaling. Therefore, we concluded that MYDGF inhibits endothelial inflammation and adhesion responses, blunts leukocyte homing, protects against endothelial injury and atherosclerosis in a manner involving MAP4K4/NF-κB signaling, and serves as a cross-talk factor between bone marrow and arteries to regulate the pathophysiology of arteries. Bone marrow functions as an endocrine organ and serves as a potential therapeutic target for metabolic disorders.

Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. To explore whether curcumin is able to ameliorate HIV-1-associated neurotoxicity, we treated a murine microglial cell line (N9) and primary rat cortical neurons with curcumin in the presence or absence of neurotoxic HIV-1 gp120 (V3 loop) protein. We found that HIV-1 gp120 profoundly induced N9 cells to produce reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). HIV-1 gp120 also induced apoptosis of primary rat cortical neurons. Curcumin exerted a powerful inhibitory effect against HIV-1 gp120-induced neuronal damage, reducing the production of ROS, TNF-α and MCP-1 by N9 cells and inhibiting apoptosis of primary rat cortical neurons. Curcumin may exert its biological activities through inhibition of the delayed rectification and transient outward potassium (K+) current, as curcumin effectively reduced HIV-1 gp120-mediated elevation of the delayed rectification and transient outward K+ channel current in neurons. We conclude that HIV-1 gp120 increases ROS, TNF-α and MCP-1 production in microglia, and induces cortical neuron apoptosis by affecting the delayed rectification and transient outward K+ channel current. Curcumin reduces production of ROS and inflammatory mediators in HIV-1-gp120-stimulated microglia, and protects cortical neurons against HIV-1-mediated apoptosis, most likely through inhibition of HIV-1 gp120-induced elevation of the delayed rectification and transient outward K+ current.

As a natural flavonoid, low-dose diet supplement of LU ameliorates diet-induced obesity and insulin resistance in mice, suggesting a new therapeutic and interventional approach for these diseases.