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Objective To investigate the role of macrophages in the process of fine particulate matter (PM2.5) exposure induced damage to pulmonary blood-air barrier. Methods Eighteen male BALB/C mice (aged of 10 weeks, weighing 24~27 g) were randomly divided into control group and low- and high-dose PM2.5 exposure groups (receiving 1.8 and 16.2 mg/kg, respectively), with 6 mice in each group. The control group received tracheal instillations of normal saline on days 1, 4, and 7, whereas the exposure groups were administered corresponding dose of PM2.5 exposure at the same time points. In 24 h after last exposure, pathological changes in the lung tissues were observed, and the contents of total protein (TP), lactate dehydrogenase (LDH), and alkaline phosphatase (AKP) in bronchoalveolar lavage fluid (BALF), and F4/80 protein level in lung tissue were measured to evaluate the blood-air barrier damage and macrophage infiltration within the lung tissues. Additionally, an in vitro model of the blood-air barrier was established using A549 alveolar epithelial cells and EA.hy926 vascular endothelial cells. In combination with a THP-1 macrophage model, the supernatant PM2.5 supernatant, macrophage supernatant, and PM2.5-macrophage supernatant were incubated with the barrier model for 24 h, respectively. Transmembrane electrical resistance (TEER), sodium fluorescein permeability of the barrier model, and LDH release from the barrier cells were measured to ascertain the extent of macrophage-mediated enhancement in barrier damage induced by PM2.5 exposure. Furthermore, the expression of inflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-8 in the macrophages after PM2.5 exposure was analyzed with quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). Results PM2.5 exposure induced lung tissue damage in mice in a dose-dependent manner, significantly elevated the contents of TP, LDH and AKP in the BALF and caused marked infiltration of macrophages into the lung tissue, especially the high-dose exposure when compared with the mice from the control group (P

Breast cancer (BrCa) is the malignant tumor that most seriously threatens female health; however, the molecular mechanism underlying its progression remains unclear. Here, we found that conditional deletion of hypermethylated in cancer 1 (HIC1) in the mouse mammary gland might contribute to premalignant transformation in the early stage of tumor formation. Moreover, the chemokine (C-X-C motif) ligand 14 (CXCL14) secreted by HIC1-deleted BrCa cells bound to its cognate receptor GPR85 on mammary fibroblasts in the microenvironment and was responsible for activating these fibroblasts via the ERK1/2, Akt, and neddylation pathways, whereas the activated fibroblasts promoted BrCa progression via the induction of epithelial-mesenchymal transition (EMT) by the C-C chemokine ligand 17 (CCL17)/CC chemokine receptor 4 (CCR4) axis. Finally, we confirmed that the HIC1-CXCL14-CCL17 loop was associated with the malignant progression of BrCa. Therefore, the crosstalk between HIC1-deleted BrCa cells and mammary fibroblasts might play a critical role in BrCa development. Exploring the progression of BrCa from the perspective of microenvironment will be beneficial for identifying the potential prognostic markers of breast tumor and providing more effective treatment strategies., IntroductionBreast cancer (BrCa) is the most frequently diagnosed malignant tumor in women worldwide and represents the main cause of cancer-related death (1). Although systematic therapeutic approaches have decreased cancer-specific mortality, [...]

Background: Gout is a common inflammatory arthritis, which is mainly caused by the deposition of monosodium urate (MSU) in tissues. Transcriptomics was used to explore the pathogenesis and treatment of gout in our work., Objective: The objective of the study was to analyze and validate potential therapeutic targets and biomarkers in THP-1 cells that were exposed to MSU., Methods: THP-1 cells were exposed to MSU. The inflammatory effect was characterized, and RNA-Seq analysis was then carried out. The differential genes obtained by RNA-Seq were analyzed with gene expression omnibus (GEO) series 160170 (GSE160170) gout-related clinical samples in the GEO database and gout-related genes in the GeneCards database. From the three analysis approaches, the genes with significant differences were verified by the differential genes' transcription levels. The interaction relationship of long non-coding RNA (lncRNA) was proposed by ceRNA network analysis., Results: MSU significantly promoted the release of IL-1β and IL-18 in THP-1 cells, which aggravated their inflammatory effect. Through RNA-Seq, 698 differential genes were obtained, including 606 differential mRNA and 92 differential `LncRNA. Cross-analysis of the RNA-Seq differential genes, the GSE160170 differential genes, and the gout-related genes in GeneCards revealed a total of 17 genes coexisting in the tripartite data. Furthermore, seven differential genes-C-X-C motif chemokine ligand 8 (CXCL8), C-X-C motif chemokine ligand 2 (CXCL2), tumor necrosis factor (TNF), C-C motif chemokine ligand 3 (CCL3), suppressor of cytokine signaling 3 (SOCS3), oncostatin M (OSM), and MIR22 host gene (MIR22HG)-were verified as key genes that analyzed the weight of genes in pathways, the enrichment of inflammationrelated pathways, and protein-protein interaction (PPI)nodes combined with the expression of genes in RNA-Seq and GSE160170. It is suggested that MIR22HG may regulate OSM and SOCS3 through microRNA 4271 (miR-4271), OSM, and SOCS3m; CCL3 through microRNA 149-3p (miR-149-3p); and CXCL2 through microRNA 4652-3p (miR-4652-3p)., Conclusion: The potential of CXCL8, CXCL2, TNF, CCL3, SOCS3, and OSM as gout biomarkers and MIR22HG as a therapeutic target for gout are proposed, which provide new insights into the mechanisms of gout biomarkers and therapeutic methods., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)