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Pancreatic cancer (PC) is a great health burden to patients owing to its poor overall survival rate. Long noncoding RNAs (lncRNAs) interact with microRNAs (miRs) to participate in tumorigenesis. Therefore, we aim to uncover the role and related mechanism of LINC00473 in PC through the modulation of miR‐195‐5p and programmed death‐ligand 1 (PD‐L1). Increased LINC00473 and PD‐L1 but declined miR‐195‐5p were determined in PC tissues and cell lines, and it was found that LINC00473 mainly situated in the cytoplasm. Also, miR‐195‐5p was verified to bind with both LINC00473 and PD‐L1. Next, with the aim to examine the ability of LINC00473, miR‐195‐5p, and PD‐L1 on the PC progression, the expression of LINC00473, miR‐195‐5p and PD‐L1 were altered with mimics, inhibitors, overexpression vectors or siRNAs in PC cells and cocultured CD8+ T cells. It was demonstrated that LINC00473 sponged miR‐195‐5p to upregulate PD‐L1 expression. More important, the obtained results revealed that LINC00473 silencing or miR‐195‐5p upregulation elevated the expression of Bcl‐2 associated X protein (Bax), interferon (IFN)‐γ, and interleukin (IL)‐4 but reduced the expression of B‐cell lymphoma‐2 (Bcl‐2), matrix metalloproteinase (MMP)‐2, MMP‐9, and IL‐10, thus inducing the enhancement of the apoptosis as along with the inhibition of proliferation, invasion, and migration of the PC cells. LINC00473 silencing or miR‐195‐5p elevation activated the CD8+ T cells. Taken together, LINC00473 silencing blocked the PC progression through enhancing miR‐195‐5p‐targeted downregulation of PD‐L1. This finding offers new therapeutic options for treating this devastating disease. [ABSTRACT FROM AUTHOR]

Hypoglossal motoneurons innervate genioglossus muscle, the contraction of which is critical in the maintenance of upper airway patency in patients with obstructive sleep apnea. As a potassium channel distributed in hypoglossal motoneurons, TWIK‐related acid‐sensitive K+ channel‐1 (TASK‐1) could be inhibited by 5‐HT. This study aimed to investigate if TASK‐1 expression in hypoglossal nucleus could be influenced by chronic intermittent hypoxia (CIH) and 5‐HT2A receptors antagonist. Two hundred twenty‐eight rats were exposed to CIH or normoxia (NO) in the presence and absence of 5‐HT 2A receptor antagonist (MDL‐100907) microinjected into the hypoglossal nucleus. The expression of 5‐HT and TASK‐1 in the hypoglossal nucleus were detected by immunohistochemistry and reverse transcription quantitative polymerase chain reaction on the 1st, 3rd, 7th, 14th and 21st day of CIH exposure. The mean optical density (MOD) of 5‐HT in the XII nucleus was significantly increased in the CIH and CIH + MDL group than the NO group on the 7th and 21st day (p < 0.05). Compared with the NO group, the MOD and gene expression of TASK‐1 in the CIH group was significantly increased on the 7th and 14th day (p < 0.05), then normalized on the 21st day. The TASK‐1 expression in the CIH + MDL group was significantly lower than the CIH + PBS and CIH group on the 7th and 14th day (p < 0.05). The CIH‐induced transiently upregulation of the TASK‐1 expression in the hypoglossal nucleus could be reversed by 5‐HT 2A receptor antagonist, indicating that the modulation of the TASK‐1 expression in response to CIH involves 5‐HT and 5‐HT 2A receptors, and this CIH effect might be 5‐HT 2A receptor‐dependent. [ABSTRACT FROM AUTHOR]

The members of the tumor necrosis factor (TNF) family play pivotal roles in the regulation of the immune system. LIGHT is a type II transmembrane protein belonging to the TNF family that was originally identified as a weak inducer of apoptosis. This cytokine has been extensively studied for its role in T cell regulation. Recently, we identified its role in inducing maturation of dendritic cells, such as LIGHT upregulated CD86 expression on dendritic cells in our previous report. However, the signal transduction pathway on this regulation remains unknown. In this study, we found that LIGHT activated NF-κB, p44/42 MAPK, but not JNK. LIGHT upregulates CD86 expression on DCs through activation of NF-κB, but not p44/42 signal pathway, because inhibition of NF-κB activity by its inhibitor could blunt the effect of LIGHT in up-regulation of CD86 expression, but neither inhibitor of p44/42 MAPK nor JNK inhibitor has this effect. Thus we demonstrate that LIGHT regulates CD86 expression through NF-κB signal transduction pathway but neither p44/42 MAPK nor JNK/AP-1 signaling pathway. We conclude that NF-κB signal plays a key role in LIGHT-mediated upregulation of CD86 expression. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We investigated whether vascular smooth muscle cells (VSMC)-derived from human produce angiotensin (Ang) II upon change from the contractile phenotype to the synthetic phenotype by incubation with fibronectin (FN). Expression of α-smooth muscle (SM) actin, apparent in the contractile phenotype, was decreased by FN. Expressions of matrix Gla and osteopontin, apparent in the synthetic phenotype, were increased by FN. Ang II measured by radioimmunoassay (RIA) was significantly increased in human VSMC by FN. Expression of mRNAs for Ang II-generating proteases cathepsin D, cathepsin G, ACE, and chymase was increased by FN. Expressions of cathepsin D and cathepsin G proteins were also increased by FN. Ang I-generating activity, which was inhibited by an aspartyl protease inhibitor pepstatin A, was readily detected in the conditioned medium from human VSMC. Antisense oligodeoxynucleotides (ODNs) that hybridize with cathepsin D and cathepsin G significantly inhibited FN-increased Ang II in conditioned medium and cell extracts. In VSMC conditioned medium, FN-induced elevation of Ang II was significantly inhibited by temocapril but not by chymostatin. Ang II type 1 receptor antagonist CV11974 completely, and antisense cathepsin D and cathepsin G ODNs partially inhibited the FN-stimulated growth of human VSMC. These results indicate that the change of homogeneous cultures of human VSMC from the contractile to the synthetic phenotype sequentially increases expression of proteases cathepsin D, cathepsin G, and ACE, production of Ang II and productions of growth factors, culminating in VSMC proliferation. These findings implicate a new mechanism for the pathogenesis of human vascular proliferative diseases. J. Cell. Physiol. 196: 284–292, 2003. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]