CCN1 Secretion Induced by Cigarette Smoking Extracts Augments IL-8 Release from Bronchial Epithelial Cells

Inflammation involves in many cigarette smoke (CS) related diseases including the chronic obstructive pulmonary disease (COPD). Lung epithelial cell released IL-8 plays a crucial role in CS induced lung inflammation. CS and cigarette smoke extracts (CSE) both induce IL-8 secretion and subsequently, IL-8 recruits inflammatory cells into the lung parenchyma. However, the molecular and cellular mechanisms by which CSE triggers IL-8 release remain not completely understood. In this study, we identified a novel extracellular matrix (ECM) molecule, CCN1, which mediated CSE induced IL-8 secretion by lung epithelial cells. We first found that CS and CSE up-regulated CCN1 expression and secretion in lung epithelial cells in vivo and in vitro. CSE up-regulated CCN1 via induction of reactive oxygen spices (ROS) and endoplasmic reticulum (ER) stress. p38 MAPK and JNK activation were also found to mediate the signal pathways in CSE induced CCN1. CCN1 was secreted into ECM via Golgi and membrane channel receptor aquaporin4. After CSE exposure, elevated ECM CCN1 functioned via an autocrine or paracrine manner. Importantly, CCN1 activated Wnt pathway receptor LRP6, subsequently stimulated Wnt pathway component Dvl2 and triggered beta-catenin translocation from cell membrane to cytosol and nucleus. Treatment of Wnt pathway inhibitor suppressed CCN1 induced IL-8 secretion from lung epithelial cells. Taken together, CSE increased CCN1 expression and secretion in lung epithelial cells via induction of ROS and ER stress. Increased ECM CCN1 resulted in augmented IL-8 release through the activation of Wnt pathway

Flotillin-2 Modulates Fas Signaling Mediated Apoptosis after Hyperoxia in Lung Epithelial Cells

Lipid rafts are subdomains of the cell membrane with distinct protein composition and high concentrations of cholesterol and glycosphingolipids. Raft proteins are thought to mediate diverse cellular processes including signal transduction. However, its cellular mechanisms remain unclear. Caveolin-1 (cav-1, marker protein of caveolae) has been thought as a switchboard between extracellular matrix (ECM) stimuli and intracellular signals. Flotillin-2/reggie-1(Flot-2) is another ubiquitously expressed raft protein which defines non-caveolar raft microdomains (planar raft). Its cellular function is largely uncharacterized. Our novel studies demonstrated that Flot-2, in conjunction with cav-1, played important functions on controlling cell death via regulating Fas pathways. Using Beas2B epithelial cells, we found that in contrast to cav-1, Flot-2 conferred cytoprotection via preventing Fas mediated death-inducing signaling complex (DISC) formation, subsequently suppressed caspase-8 mediated extrinsic apoptosis. Moreover, Flot-2 reduced the mitochondria mediated intrinsic apoptosis by regulating the Bcl-2 family and suppressing cytochrome C release from mitochondria to cytosol. Flot-2 further modulated the common apoptosis pathway and inhibited caspase-3 activation via up-regulating the members in the inhibitor of apoptosis (IAP) family. Last, Flot-2 interacted with cav-1 and limited its expression. Taken together, we found that Flot-2 protected cells from Fas induced apoptosis and counterbalanced the pro-apoptotic effects of cav-1. Thus, Flot-2 played crucial functions in cellular homeostasis and cell survival, suggesting a differential role of individual raft proteins

In-Plane Strengthening of Unreinforced Masonry Walls by Glass Fiber-Reinforced Polyurea

Strengthening techniques have been employed in Korea to unreinforced masonry walls (UMWs) for several years to protect them from damage caused by the intermittent occurrence of earthquakes. Polyurea, which has a high tensile strength and elongation rate, can be utilized as a strengthening material to enhance the in-plane strength and ductility of UMWs. Glass fiber-reinforced polyurea (GFRPU) is a composite elastomer manufactured by progressively adding milled glass fiber to polyurea. The purpose of this study is to investigate the enhancement of the in-plane strength and ductility of UMWs using GFRPU, depending on the shape of the GFRPU coating on the wall. Four masonry wall specimens are tested with test variables of the number of strengthening sides and coating shapes. It is illustrated that the GFRPU reinforcement of masonry wall leads to enhanced load-carrying capacity, ductility, and energy absorption. An empirical formula to represent the degree of strengthening effected by GFRPU is proposed in this study. Doi: 10.28991/cej-2021-03091782 Full Text: PD

Out-of-Plane Strengthening of Unreinforced Masonry Walls by Glass Fiber-Reinforced Polyurea

Fiber-reinforced polymer reinforcement or polyurea reinforcement techniques are applied to strengthen unreinforced masonry walls (UMWs). The purpose of this experimental study is to verify the out-of-plane reinforcing effect of sprayed glass fiber-reinforced polyurea (GFRPU), which is a composite elastomer made of polyurea and milled glass fibers on UMW. The out-of-plane strengths and ductile behaviors based on various coating shapes are compared in this study. An empirical formula to describe the degree of reinforcement on the out-of-plane strength of the UMW is derived based on the experimental results. It is observed that the peak load-carrying capacity, ductility, and energy absorption capacity gradually improve with an increase in the strengthening degree or area. Compared with the existing masonry wall reinforcement method, the GFRPU technique is a construction method that can help improve the safety performance along with ease of construction and economic efficiency. Doi: 10.28991/CEJ-2022-08-01-011 Full Text: PD

Autophagy in Idiopathic Pulmonary Fibrosis

Background: Autophagy is a basic cellular homeostatic process important to cell fate decisions under conditions of stress. Dysregulation of autophagy impacts numerous human diseases including cancer and chronic obstructive lung disease. This study investigates the role of autophagy in idiopathic pulmonary fibrosis. Methods: Human lung tissues from patients with IPF were analyzed for autophagy markers and modulating proteins using western blotting, confocal microscopy and transmission electron microscopy. To study the effects of TGF-β1 on autophagy, human lung fibroblasts were monitored by fluorescence microscopy and western blotting. In vivo experiments were done using the bleomycin-induced fibrosis mouse model. Results: Lung tissues from IPF patients demonstrate evidence of decreased autophagic activity as assessed by LC3, p62 protein expression and immunofluorescence, and numbers of autophagosomes. TGF-β1 inhibits autophagy in fibroblasts in vitro at least in part via activation of mTORC1; expression of TIGAR is also increased in response to TGF-β1. In the bleomycin model of pulmonary fibrosis, rapamycin treatment is antifibrotic, and rapamycin also decreases expression of á-smooth muscle actin and fibronectin by fibroblasts in vitro. Inhibition of key regulators of autophagy, LC3 and beclin-1, leads to the opposite effect on fibroblast expression of á-smooth muscle actin and fibronectin. Conclusion: Autophagy is not induced in pulmonary fibrosis despite activation of pathways known to promote autophagy. Impairment of autophagy by TGF-β1 may represent a mechanism for the promotion of fibrogenesis in IPF

Small Bowel Volvulus Induced by Mesenteric Lymphangioma in an Adult: a Case Report

Mesenteric lymphangiomas are rare abdominal masses that are seldom associated with small bowel volvulus, and especially in adult patients. We report here on an unusual case of small bowel volvulus that was induced by a mesenteric lymphangioma in a 43-year-old man who suffered from repeated bouts of abdominal pain. At multidetector CT, we noticed whirling of the cystic mesenteric mass and the adjacent small bowel around the superior mesenteric artery. Small bowel volvulus induced by the rotation of the mesenteric lymphangioma was found on exploratory laparotomy. Lymphangioma should be considered as a rare cause of small bowel volvulus in adult patients

The combination effect of sodium butyrate and 5-Aza-2'-deoxycytidine on radiosensitivity in RKO colorectal cancer and MCF-7 breast cancer cell lines

<p>Abstract</p> <p>Background</p> <p>The overall level of chromatin compaction is an important mechanism of radiosensitivity, and modification of DNA methylation and histone deacetylation may increase radiosensitivity by altering chromatin compaction. In this study, we investigated the effect of a demethylating agent, a histone deacetylase(HDAC) inhibitor, and the two agents combined on radiosensitivity in human colon and breast cancer cell lines.</p> <p>Methods</p> <p>In this study, we used RKO colorectal cancer cell line and MCF-7 breast cancer cell lines and normal colon cell lines. On each of the cell lines, we used three different agents: the HDAC inhibitor sodium butyrate(SB), the demethylating agent 5-Aza-2'-deoxycytidine(5-aza-DC), and radiation. We then estimated the percentage of the cell survival using the XTT method and experimented to determine if there was an augmentation in the therapeutic effect by using different combinations of the two or three of the treatment methods.</p> <p>Results</p> <p>After treatment of each cell lines with 5-aza-DC, SB and 6 grays of radiation, we observed that the survival fraction was lower after the treatment with 5-aza-DC or SB than with radiation alone in RKO and MCF-7 cell lines(p < 0.001). The survival fraction was lowest when the two agents, 5-aza-DC and SB were combined with radiation in both RKO and MCF-cell lines.</p> <p>Conclusion</p> <p>In conclusion, 5-aza-DC and SB can enhance radiosensitivity in both MCF-7 and RKO cell lines. The combination effect of a demethylating agent and an HDAC inhibitor is more effective than that of single agent treatment in both breast and colon cancer cell lines.</p

Clinical effect of double coaxial self-expandable metallic stent in management of malignant colon obstruction

PURPOSEWe aimed to evaluate the clinical effectiveness and safety of double coaxial self-expandable metallic stent (DCSEMS) in management of malignant colonic obstruction as a bridge to surgery or palliation for inoperable patients.METHODSBetween April 2006 and December 2012, 49 patients (27 males and 22 females; median age, 68 years; age range, 38–91 years) were selected to receive decompressive therapy for malignant colonic obstruction by implanting a DCSEMS. Application of DCSEMS was attempted in 49 patients under fluoroscopic guidance. The obstruction was located in the transverse colon (n=2), descending colon (n=7), sigmoid colon (n=24), rectosigmoid junction (n=6), and the rectum (n=10). The intended use of DCSEMS was as a bridge to elective surgery in 23 patients and palliation in 26 patients.RESULTSClinical success, defined as >50% dilatation of the stent with subsequent symptomatic improvement, was achieved in 48 of 49 patients (98%). The stent was properly inserted in all patients. No immediate major procedure-related complications occurred. One patient in the bridge-to-surgery group had colon perforation three days after DCSEMS application. Four patients had late migrations of the double stent.CONCLUSIONApplication of DCSEMS is safe and effective in management of malignant colonic obstruction; it prevents stent migration and tumor ingrowth and lowers perforation rate during the stent application