LncRNA CDKN2B-AS1 contributes to glioma development by regulating the miR-199a-5p/DDR1 axis.

BACKGROUND: Although cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) is upregulated in glioma, its function and potential mechanism in glioma remain unclear. METHODS: CDKN2B-AS1 level in glioma tissues and cell lines LN229, U251, and U87 was measured by qRT-PCR. Loss-of-function assays using short hairpin RNA for CDKN2B-AS1 (sh-CDKN2B-AS1) were performed to evaluate the effect of CDKN2B-AS1 on cell invasion, migration, proliferation, and apoptosis. The relationship among CDKN2B-AS1, miR-199a-5p, and DDR1 was determined by bioinformatics analysis and luciferase reporter assay. Rescue experiments were conducted to explore the function of CDKN2B-AS1 and miR-199a-5p in glioma. An in vivo animal model of lentivirally transduced U87 glioma xenografts in mice was established to confirm the role of CDKN2B-AS1. RESULTS: CDKN2B-AS1 is significantly upregulated in glioma tissues and cell lines. CDKN2B-AS1 knockdown significantly inhibits cell proliferation, invasion, and migration, while promoting apoptosis of glioma cell lines U251 and U87. Further, a miR-199a-5p inhibitor attenuates the inhibitory effects of sh-CDKN2B-AS1 on these cell phenotypes. CDKN2B-AS1 positively regulates DDR1 expression by directly sponging miR-199a-5p. Moreover, CDKN2B-AS1 knockdown efficiently inhibits U87 tumor xenograft growth in mice. CONCLUSION: Our study reveals that CDKN2B-AS1 promotes glioma development by regulating the miR-199a-5p/DDR1 axis, suggesting that this lncRNA might be a potential therapeutic target.

Protectin DX promotes epithelial injury repair and inhibits fibroproliferation partly via ALX/PI3K signalling pathway.

Acute respiratory distress syndrome/acute lung injury (ARDS/ALI) is histologically characterized by extensive alveolar barrier disruption and excessive fibroproliferation responses. Protectin DX (PDX) displays anti-inflammatory and potent inflammation pro-resolving actions. We sought to investigate whether PDX attenuates LPS (lipopolysaccharide)-induced lung injury via modulating epithelial cell injury repair, apoptosis and fibroblasts activation. In vivo, PDX was administered intraperitoneally (IP) with 200 ng/per mouse after intratracheal injection of LPS, which remarkedly stimulated proliferation of type II alveolar epithelial cells (AT II cells), reduced the apoptosis of AT II cells, which attenuated lung injury induced by LPS. Moreover, primary type II alveolar cells were isolated and cultured to assess the effects of PDX on wound repair, apoptosis, proliferation and transdifferentiation in vitro. We also investigated the effects of PDX on primary rat lung fibroblast proliferation and myofibroblast differentiation. Our result suggests PDX promotes primary AT II cells wound closure by inducing the proliferation of AT II cells and reducing the apoptosis of AT II cells induced by LPS, and promotes AT II cells transdifferentiation. Furthermore, PDX inhibits transforming growth factor-ß1 (TGF-ß1 ) induced fibroproliferation, fibroblast collagen production and myofibroblast transformation. Furthermore, the effects of PDX on epithelial wound healing and proliferation, fibroblast proliferation and activation partly via the ALX/ PI3K signalling pathway. These data present identify a new mechanism of PDX which targets the airway epithelial cell and fibroproliferation are potential for treatment of ARDS/ALI.

Case report: Endovascular intervention of internal carotid artery pseudoaneurysm secondary to nasopharyngeal carcinoma radiotherapy.

Background: Internal carotid artery pseudoaneurysm (PSA) is a serious complication after radiotherapy for nasopharyngeal carcinoma, and once it ruptures and bleeds, it will seriously affect the patient's survival and prognosis. However, because of its relatively low incidence, many medical institutions lack experience in managing this type of emergency. Case information: In this case report, we described two cases suffered ruptured internal carotid artery PSA after radiotherapy for nasopharyngeal carcinoma, including their history, diagnosis, and treatment. Both cases underwent emergency endovascular interventions, one of which with long-term healing after embolization of the PSA, and the other one with re-bleeding after embolization and was eventually stopped by embolization of the parent artery. Ultimately, both cases received timely and effective treatment. Conclusion: This case report detailed the diagnosis and treatment course of internal carotid artery PSA after radiotherapy for nasopharyngeal carcinoma, which enhanced the understanding of this emergency, and provided valuable information and experience for the treatment strategy of similar PSA on the internal carotid artery.

Protectin DX promotes the inflammatory resolution via activating COX-2/L-PGDS-PGD2 and DP1 receptor in acute respiratory distress syndrome.

PURPOSE: Acute respiratory distress syndrome (ARDS) is characterized by uncontrollable inflammation. Cyclooxygenase-2(COX-2) and its metabolite prostaglandins are known to promote the inflammatory resolution of ARDS. Recently, a newly discovered endogenous lipid mediator, Protectin DX (PDX), was also shown to mediate the resolution of inflammation. However, the regulatory of PDX on the pro-resolving COX-2 in ARDS remains unknown. MATERIAL AND METHODS: PDX (5 µg/kg) was injected into rats intravenously 12 h after the lipopolysaccharide (LPS, 3 mg/kg) challenge. Primary rat lung fibroblasts were incubated with LPS (1 µg/ml) and/or PDX (100 nM). Lung pathological changes examined using H&E staining. Protein levels of COX-2, PGDS and PGES were evaluated using western blot. Inflammatory cytokines were tested by qPCR, and the concentration of prostaglandins measured by using ELISA. RESULTS: Our study revealed that, COX-2 and L-PGDS has biphasic activation characteristics that LPS could induce induced by LPS both in vivo and in vitro.. The secondary peak of COX-2, L-PGDS-PGD2 promoted the inflammatory resolution in ARDS model with the DP1 receptor being activated and PDX up-regulated the inflammatory resolutionvia enhancing the secondary peak of COX-2/L-PGDS-PGD2 and activating the DP1 receptor. CONCLUSION: PDX promoted the resolution of inflammation of ARDS model via enhancing the expression of secondary peak of COX-2/L-PGDS-PGD2 and activating the DP1 receptor. PDX shows promising therapeutic potential in the clinical management of ARDS.