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https://www.readbyqxmd.com/read/29050006/recent-insights-into-the-biological-functions-of-sestrins-in-health-and-disease
#1
Menglong Wang, Yao Xu, Jianfang Liu, Jing Ye, Wenhui Yuan, Huimin Jiang, Zhen Wang, Hong Jiang, Jun Wan
Sestrins (Sesns) have been identified as a family of highly conserved stress-inducible proteins that are strongly up-regulated by various stresses, including DNA damage, oxidative stress, and hypoxia. The Sesns play protective roles in most physiological and pathological conditions mainly through the regulation of oxidative stress, inflammation, autophagy, endoplasmic reticulum stress, and metabolic homeostasis. In this review, we discussed the possible regulators of Sesns expression, such as p53, forkhead box O, nuclear factor erythroid 2 like 2 (Nrf2), NH (2)-terminal kinase (JNK)/c-Jun pathway and hypoxia-inducible factor-1α (Hif-1α), and the downstream pathways regulated by the Sesns including AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, mitogen-activated protein kinases (MAPKs) signaling, Nrf2 signaling, NADPH oxidase signaling and transforming growth factor β (TGF-β) signaling in heart diseases, lung diseases, gastrointestinal tract diseases, liver and metabolism diseases, neurological diseases, kidney diseases and immunological diseases...
October 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29045477/tubastatin-ameliorates-pulmonary-fibrosis-by-targeting-the-tgf%C3%AE-pi3k-akt-pathway
#2
Shigeki Saito, Yan Zhuang, Bin Shan, Svitlana Danchuk, Fayong Luo, Martina Korfei, Andreas Guenther, Joseph A Lasky
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal disease. Histone deacetylase 6 (HDAC6) alters function and fate of various proteins via deacetylation of lysine residues, and is implicated in TGF-β1-induced EMT (epithelial-mesenchymal transition). However, the role of HDAC6 in pulmonary fibrosis is unknown. METHODS: HDAC6 expression in IPF and control lungs was assessed by quantitative real-time PCR (qRT-PCR) and immunoblots. Lung fibroblasts were treated with TGF-β1 ± HDAC6 inhibitors (Tubacin, Tubastatin, ACY1215, or MC1568), and fibrotic markers such as type I collagen were assessed using qRT-PCR and immunoblots...
2017: PloS One
https://www.readbyqxmd.com/read/29044946/aquaporin-1-inhibition-reduces-metastatic-formation-in-a-mouse-model-of-melanoma
#3
Laura Simone, Concetta Domenica Gargano, Francesco Pisani, Antonio Cibelli, Maria Grazia Mola, Antonio Frigeri, Maria Svelto, Grazia Paola Nicchia
Aquaporin-1 (AQP1) is a proangiogenic water channel protein promoting endothelial cell migration. We previously reported that AQP1 silencing by RNA interference reduces angiogenesis-dependent primary tumour growth in a mouse model of melanoma. In this study, we tested the hypothesis that AQP1 inhibition also affects animal survival and lung nodule formation. Melanoma was induced by injecting B16F10 cells into the back of C57BL6J mice. Intratumoural injection of AQP1 siRNA and CTRL siRNA was performed 10 days after tumour cell implantation...
October 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29029445/microrna-200c-increases-radiosensitivity-of-human-cancer-cells-with-activated-egfr-associated-signaling
#4
Taeryool Koo, Bong Jun Cho, Dan Hyo Kim, Ji Min Park, Eun Jung Choi, Hans H Kim, David J Lee, In Ah Kim
MicroRNA-200c (miR-200c) recently was found to have tumor-suppressive properties by inhibiting the epithelial-mesenchymal transition (EMT) in several cancers. miR-200c also interacts with various cellular signaling molecules and regulates many important signaling pathways. In this study, we investigated the radiosensitizing effect of miR-200c and its mechanism in a panel of human cancer cell lines. Malignant glioma (U251, T98G), breast cancer (MDA-MB-468), and lung carcinoma (A549) cells were transfected with control pre-microRNA, pre-miR-200c, or anti-miR-200c...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28965583/the-copper-dependent-lysyl-oxidases-contribute-to-the-pathogenesis-of-pulmonary-emphysema-in-chronic-obstructive-pulmonary-disease-patients
#5
Neziha Besiktepe, Ozgecan Kayalar, Ezel Ersen, Fusun Oztay
Abnormalities in the elastic fiber biology are seen in pulmonary emphysema (PE). The copper-dependent lysyl oxidases regulate the production and accumulation of elastic fibers in the connective tissue. This study focused on the relationship between lysyl oxidase (LOX), LOX-like protein 1 (LOXL1), and LOXL2 and PE pathogenesis. Lung samples with or without PE from patients with chronic obstructive lung disease (n=35) were used. Protein levels of elastin, LOX, LOXL1, LOXL2, hypoxia inducible factor 1-alpha (HIF-1α), copper metabolism domain containing-1 (COMMD1), and phosphatase and tensin homolog (PTEN) were assayed using microscopic and biochemical methods The emphysematous areas were characterized by enlargement of the alveoli, destruction of the alveolar structure, accumulation of macrophages in the alveolar lumens, and showed increased HIF-1α immunoreactivity...
December 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28965117/quercetin-inhibits-cell-migration-and-invasion-in-human-osteosarcoma-cells
#6
Haifeng Lan, Wei Hong, Pan Fan, Dongyang Qian, Jianwei Zhu, Bo Bai
BACKGROUND/AIMS: Osteosarcoma is a malignant tumor associated with high mortality; however, no effective therapies for the disease have been developed. Several studies have focused on elucidating the pathogenesis of osteosarcoma and have aimed to develop novel therapies for the disease. Quercetin is a vital dietary flavonoid that has been shown to have a variety of anticancer effects, as it induces cell cycle arrest, apoptosis, and differentiation and is involved in cell adhesion, metastasis and angiogenesis...
September 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28961193/fascaplysin-exerts-anti-cancer-effects-through-the-downregulation-of-survivin-and-hif-1%C3%AE-and-inhibition-of-vegfr2-and-trka
#7
Taek-In Oh, Yoon-Mi Lee, Taek-Jin Nam, Young-San Ko, Shinmee Mah, Jinhee Kim, Younghoon Kim, Rallabandi Harikrishna Reddy, Young Jun Kim, Sungwoo Hong, Ji-Hong Lim
Fascaplysin has been reported to exert anti-cancer effects by inhibiting cyclin-dependent kinase 4 (CDK4); however, the precise mode of action by which fascaplysin suppresses tumor growth is not clear. Here, we found that fascaplysin has stronger anti-cancer effects than other CDK4 inhibitors, including PD0332991 and LY2835219, on lung cancer cells that are wild-type or null for retinoblastoma (RB), indicating that unknown target molecules might be involved in the inhibition of tumor growth by fascaplysin. Fascaplysin treatment significantly decreased tumor angiogenesis and increased cleaved-caspase-3 in xenografted tumor tissues...
September 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28956952/role-of-the-aryl-hydrocarbon-receptor-in-sugen-5416-induced-experimental-pulmonary-hypertension
#8
Afshan Dean, Teja Gregorc, Craig K Docherty, Katie Y Harvey, Margaret Nilsen, Nicholas W Morrell, Margaret R MacLean
RATIONALE: Rats dosed with the vascular endothelial growth factor (VEGF) inhibitor Sugen 5416 (Su), placed in hypoxia then restored to normoxia has become a widely used model of pulmonary arterial hypertension (PAH). The mechanism by which Su exaccerbates pulmonary hypertension is, however, unclear. OBJECTIVES: We investigated Su-activation of the aryl hydrocarbon receptor (AhR) in patient human pulmonary arterial smooth muscle cells (hPASMCs) and patient blood outgrowth endothelial cells (BOECs)...
September 28, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28951129/ras-inhibitors-display-an-anti-metastatic-effect-by-downregulation-of-lysyl-oxidase-through-inhibition-of-the-ras-pi3k-akt-hif-1%C3%AE-pathway
#9
Yoko Yoshikawa, Osamu Takano, Ichiro Kato, Yoshihisa Takahashi, Fumi Shima, Tohru Kataoka
Metastasis stands as the major obstacle for the survival from cancers. Nonetheless most existing anti-cancer drugs inhibit only cell proliferation, and discovery of agents having both anti-proliferative and anti-metastatic properties would be more beneficial. We previously reported the discovery of small-molecule Ras inhibitors, represented by Kobe0065, that displayed anti-proliferative activity on xenografts of human colorectal cancer (CRC) cell line SW480 carrying the K-ras(G12V)gene. Here we show that treatment of cancer cells carrying the activated ras genes with Kobe0065 or a siRNA targeting Ras downregulates the expression of lysyl oxidase (LOX), which has been implicated in metastasis...
September 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28949968/normalisation-of-surfactant-protein-a-and-b-expression-in-the-lungs-of-low-birth-weight-lambs-by-21-days-old
#10
Jia Yin Soo, Sandra Orgeig, Erin Victoria McGillick, Song Zhang, I Caroline McMillen, Janna L Morrison
Intrauterine growth restriction (IUGR) induced by placental restriction (PR) in the sheep negatively impacts lung and pulmonary surfactant development during fetal life. Using a sheep model of low birth weight (LBW), we found that there was an increase in mRNA expression of surfactant protein (SP)-A, -B and -C in the lung of LBW lambs but no difference in the protein expression of SP-A or -B. LBW also resulted in increased lysosome-associated membrane glycoprotein (LAMP)-3 mRNA expression, which may indicate an increase in either the density of type II Alveolar epithelial cells (AEC) or maturity of type II AECs...
2017: PloS One
https://www.readbyqxmd.com/read/28945477/epithelial-barrier-regulation-by-hypoxia-inducible-factor
#11
Louise E Glover, Sean P Colgan
Mucosal tissues represent surfaces that are exposed to the outside world and provide a conduit for internal and external communication. Tissues such as the intestine and the lung are lined by layer(s) of epithelial cells that, when organized in three dimensions, provide a critical barrier to the flux of luminal contents. This selective barrier is provided through the regulated expression of junctional proteins and mucins. Tissue oxygen metabolism is central to the maintenance of homeostasis in the mucosa. In some organs (e...
September 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28918043/mir-206-133b-cluster-a-weapon-against-lung-cancer
#12
REVIEW
Jing-Yu Pan, Cheng-Cao Sun, Zhuo-Yue Bi, Zhen-Long Chen, Shu-Jun Li, Qing-Qun Li, Yu-Xuan Wang, Yong-Yi Bi, De-Jia Li
Lung cancer is a deadly disease that ends numerous lives around the world. MicroRNAs (miRNAs) are a group of non-coding RNAs involved in a variety of biological processes, such as cell growth, organ development, and tumorigenesis. The miR-206/133b cluster is located on the human chromosome 6p12.2, which is essential for growth and rebuilding of skeletal muscle. The miR-206/133b cluster has been verified to be dysregulated and plays a crucial role in lung cancer. miR-206 and miR-133b participate in lung tumor cell apoptosis, proliferation, migration, invasion, angiogenesis, drug resistance, and cancer treatment...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28901751/sulfate-aerosols-promote-lung-cancer-metastasis-by-epigenetically-regulating-the-epithelial-to-mesenchymal-transition-emt
#13
Yang Yun, Rui Gao, Huifeng Yue, Lin Guo, Guangke Li, Nan Sang
Secondary inorganic aerosols (SIA), particularly sulfate aerosols, are central particulate matter (PM) constituents of severe haze formation in China and exert profound impacts on human health; however, our understanding of the mechanisms by which sulfate aerosols cause malignancy in lung carcinogenesis remains incomplete. Here, we show that exposure to secondary inorganic aerosols induced the invasion and migration of lung epithelial cells, and that (NH4)2SO4 exerted the most serious effects in vitro and promoted lung tumor metastasis in vivo...
September 13, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28900510/egln1-c-myc-induced-lymphoid-specific-helicase-inhibits-ferroptosis-through-lipid-metabolic-gene-expression-changes
#14
Yiqun Jiang, Chao Mao, Rui Yang, Bin Yan, Ying Shi, Xiaoli Liu, Weiwei Lai, Yating Liu, Xiang Wang, Desheng Xiao, Hu Zhou, Yan Cheng, Fenglei Yu, Ya Cao, Shuang Liu, Qin Yan, Yongguang Tao
Ferroptosis is a newly discovered form of non-apoptotic cell death in multiple human diseases. However, the epigenetic mechanisms underlying ferroptosis remain poorly defined. First, we demonstrated that lymphoid-specific helicase (LSH), which is a DNA methylation modifier, interacted with WDR76 to inhibit ferroptosis by activating lipid metabolism-associated genes, including GLUT1, and ferroptosis related genes SCD1 and FADS2, in turn, involved in the Warburg effect. WDR76 targeted these genes expression in dependent manner of LSH and chromatin modification in DNA methylation and histone modification...
2017: Theranostics
https://www.readbyqxmd.com/read/28865600/the-association-of-genetic-polymorphisms-of-hypoxia-inducible-factor-1-alpha-and-vascular-endothelial-growth-factor-with-increased-risk-of%C3%A2-chronic-obstructive-pulmonary-disease-a%C3%A2-case-control-study
#15
Zhen-Gang Yu, Bing-Zhe Wang, Zhao-Zhong Cheng
Accumulated data over the years have suggested that hypoxia inducible factor-1 alpha (HIF-1α) and its downstream vascular endothelial growth factor (VEGF) gene may be linked with chronic obstructive pulmonary disease (COPD). This study aims to investigate the association of HIF-1α and VEGF genetic polymorphisms and their correlated risks with COPD. COPD patients (case group) and healthy individuals (control group) were recruited. DNA was extracted to detect HIF-1α and VEGF genetic polymorphisms. Basal lung volume and forced expiratory capacity in 1st second (FEV1)/forced vital capacity (FVC) and FEV1/predicted value (pred)% were calculated...
September 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28856747/anticancer-effects-of-a-korean-herbal-medicine-formula-h9-via-ampk-and-her2-pi3k-akt-signaling-in-breast-cancer-cells
#16
Ju-Hee Lee, Young Hoon Son, Young-Won Kwon, Sung Yun Park, Byung-Soo Koo, Seung Hyun Jung
An H9 is a formula of nine medicinal herbs derived from Osuyubujaijung-tang, a traditional Korean prescription for Soeumin constitution. In our previous study, H9 showed anticancer effects against breast cancer and non-small-cell lung cancer. However, the underlying mechanisms of these effects have not yet been elucidated. In this study, we investigated the effects of H9, both alone and in combination with trastuzumab, on breast cancer cells and sought to elucidate the mechanisms involved. H9 suppressed the proliferation of human breast cancer cells, induced arrest of the cell cycle at the G0/G1 phase, and caused mitochondrial dysfunction and apoptosis...
August 30, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28855210/cd73-promotes-resistance-to-her2-erbb2-antibody-therapy
#17
Martin Turcotte, David Allard, Deepak Mittal, Yacine Bareche, Laurence Buisseret, Vinu José, Sandra Pommey, Vincent Delisle, Sherene Loi, Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Christos Sotiriou, Mark J Smyth, John Stagg
Expression of the ectonucleotidase CD73 by tumor cells, stromal cells, and immune cells is associated in cancer with immune suppression. In this study, we investigated the role of CD73 on the activity of the anti-HER2/ErbB2 monoclonal antibody (mAb) trastuzumab. In a prospective, randomized phase III clinical trial evaluating the activity of trastuzumab, high levels of CD73 gene expression were associated significantly with poor clinical outcome. In contrast, high levels of PD-1 and PD-L1 were associated with improved clinical outcome...
October 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28838387/tr3-is-involved-in-hypoxia-induced-apoptosis-resistance-in-lung-cancer-cells-downstream-of-hif-1%C3%AE
#18
Christoph Wohlkoenig, Katharina Leithner, Andrea Olschewski, Horst Olschewski, Andelko Hrzenjak
OBJECTIVES: Lung cancer is the leading cause of cancer death worldwide. Like in all solid tumors, hypoxia is common in lung cancer and contributes to apoptosis, and thus chemotherapy resistance. However, the underlying mechanisms are not entirely clear. TR3 (NR4A1, Nur77) is an orphan nuclear receptor that induces apoptosis and may mediate chemotherapy-induced apoptosis in cancer cells. MATERIALS AND METHODS: We used A549, H23 and H1299 cell lines to investigate how TR3-mediated apoptosis is affected by hypoxia in non-small cell lung cancer (NSCLC) cells...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28835201/irak-m-alters-the-polarity-of-macrophages-to-facilitate-the-survival-of-mycobacterium-tuberculosis
#19
Pei Shen, Quan Li, Jilei Ma, Maopeng Tian, Fei Hong, Xinjie Zhai, Jianrong Li, Hanju Huang, Chunwei Shi
BACKGROUND: Intracellular bacterium, Mycobacterium tuberculosis (M. tb), infects specifically macrophages as host cells. IRAK-M, a member of IRAK family, is a negative regulator in TLR signaling and specifically expresses in monocytes and macrophages. The role of IRAK-M in intracellular growth of M. tb and macrophage polarization was explored, for deeply understanding the pathogenesis of M. tb, the significance of IRAK-M to innate immunity and pathogen-host interaction. METHODS: IRAK-M expression was detected in M...
August 23, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28819223/levobuipivacaine-induced-dissemination-of-a549-lung-cancer-cells
#20
Shun-Ming Chan, Bo-Feng Lin, Chih-Shung Wong, Wen-Ting Chuang, Yu-Ting Chou, Zhi-Fu Wu
While anaesthetics are frequently used on cancer patients during surgical procedures, their consequence on cancer progression remains to be elucidated. In this study, we sought to investigate the influence of local anesthetics on lung cancer cell dissemination in vitro and in vivo. A549 human non-small lung cancer cells were treated with various local anaesthetics including ropivacaine, lidocaine, levobupivacaine and bupivacaine. Cell barrier property was assessed using an electric cell-substrate impedance sensing (ECIS) system...
August 17, 2017: Scientific Reports
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