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Hif lung

Minghui Ou, Xuezhi Sun, Jiancheng Liang, Fei Liu, Liqin Wang, Xiaomin Wu, Jie Tu
A water-soluble polysaccharide (STPC2) was isolated from the boiling-water extract of Sargassum thunbergii, purified by CaCl2 precipitation and chromatography on DEAE-cellulose and Sephacryl S-300 column. It was found that STPC2, with a molecular weight of 57kD, was composed of fucose, xylose, galactose and glucuronic acid, in a ratio of 8.1: 3.8: 2.1: 1.0. Additionally, we found that STPC2 significantly inhibited endothelial cell migration and tube formation without toxicity. Moreover, STPC2 significantly inhibited lung cancer cell A549 migration and proliferation...
October 17, 2016: International Journal of Biological Macromolecules
Ho Shin Kim, Mannkyu Hong, Jihyae Ann, Suyoung Yoon, Cong-Truong Nguyen, Su-Chan Lee, Ho-Young Lee, Young-Ger Suh, Ji Hae Seo, Hoon Choi, Jun Yong Kim, Kyu-Won Kim, Joohwan Kim, Young-Myeong Kim, So-Jung Park, Hyun-Ju Park, Jeewoo Lee
Based on the lead compound L-80 (compound 2), a potent heat shock protein 90 (HSP90) inhibitor, a series of C-ring truncated deguelin analogs were designed, synthesized and evaluated for Hypoxia Inducible Factor-1α (HIF-1α) inhibition as a primary screening method. Their structure-activity relationship was investigated in a systematic manner by varying the A/B ring, linker and D/E ring, respectively. Among the synthesized inhibitors, compound 5 exhibited potent HIF-1α inhibition in a dose-dependent manner and significant antitumor activity in human non-small cell lung carcinoma (H1299), with better activities than L-80...
September 30, 2016: Bioorganic & Medicinal Chemistry
Yujiro Matsuishi, Subrina Jesmin, Satoru Kawano, Sakuramoto Hideaki, Nobutake Shimojo, Chishimba Nathan Mowa, Shila Akhtar, Sohel Zaedi, Tanzila Khatun, Yoshiya Tsunoda, Takumi Kiwamoto, Nobuyuki Hizawa, Yoshiaki Inoue, Taro Mizutani
Among the dysfunctions and pathologies associated with sepsis, the underlying molecular mechanisms of sepsis-induced acute lung injury (ALI) are poorly understood. Endothelin (ET)-1, a potent vasoconstrictor and pro-inflammatory peptide, is known to be involved in the pathogenesis of ALI in a rat model of sepsis. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting β-blocker, plays a crucial role in ameliorating and attenuating LPS-induced ALI through modulation of the ET-1 system. Male Wistar rats at 8weeks of age were administered with either saline or lipopolysaccharide (LPS) for three hours (3h) and some of the LPS-administered rats were continuously treated with landiolol for 3h...
October 11, 2016: Life Sciences
Hiroki Daijo, Yuma Hoshino, Shinichi Kai, Kengo Suzuki, Kenichiro Nishi, Yoshiyuki Matsuo, Hiroshi Harada, Kiichi Hirota
Cigarette smoke (CS) is a major contributor to the development of a large number of fatal and debilitating disorders. However, the precise molecular mechanisms underlying the effects of CS in lung disease are largely unknown. To elucidate these pathophysiological processes, we examined the in vitro and in vivo effects of CS extract (CSE) and CS on the transcription factor, hypoxia-inducible factor 1 (HIF-1). CSE induced concentration- and time-dependent accumulation of HIF-1α protein in human lung epithelial-like cells under non-hypoxic conditions...
September 29, 2016: Scientific Reports
Yuh-Feng Lin, I-Jen Chiu, Fong-Yu Cheng, Yu-Hsuan Lee, Ying-Jan Wang, Yung-Ho Hsu, Hui-Wen Chiu
BACKGROUND: Zinc oxide nanoparticles (ZnO NPs) are used in an increasing number of products, including rubber manufacture, cosmetics, pigments, food additives, medicine, chemical fibers and electronics. However, the molecular mechanisms underlying ZnO NP nephrotoxicity remain unclear. In this study, we evaluated the potential toxicity of ZnO NPs in kidney cells in vitro and in vivo. RESULTS: We found that ZnO NPs were apparently engulfed by the HEK-293 human embryonic kidney cells and then induced reactive oxygen species (ROS) generation...
September 27, 2016: Particle and Fibre Toxicology
M Lan, T Xu, J Yue, J Yang, D R Gomez, M D Jeter, Q N Nguyen, Q Shi, S M Hahn, R U Komaki, X Wang, Z Liao
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Wei Lei, Yuan He, Xiaorong Shui, Guoming Li, Guosen Yan, Yu Zhang, Shian Huang, Can Chen, Yuanlin Ding
Pulmonary arterial hypertension (PAH) is characterized by endothelial dysfunction and structural remodeling of the pulmonary vasculature, mediated initially by reduced oxygen availability in the lungs. Hypoxia inducible factor (HIF), consisting of the functional subunit, HIF‑1α, and the constitutively expressed HIF‑1β, is involved in the pathological processes associated with hypoxia. In the current study, the sequences of cDNAs and amino acids of HIF were characterized and analyzed using online bioinformatics tools...
September 20, 2016: Molecular Medicine Reports
Kotaro Higashi, Toshiaki Yamagishi, Yoshimichi Ueda, Yasuhito Ishigaki, Miyako Shimasaki, Yuka Nakamura, Manabu Oguchi, Tsutomu Takegami, Motoyasu Sagawa, Hisao Tonami
OBJECTIVES: Hypoxia is a key element involved in the development and progression of tumors. HIF-1α may transiently induce and mediate the response to acute and severe hypoxia, while HIF-2α may induce a longer response and may control the response to chronic and moderate hypoxia. Hypoxia increases the cellular uptake of FDG. Therefore, HIF may play an important role in the process of the cellular uptake of FDG. The aim of this study was to compare HIF-1α/HIF-2α expression with FDG uptake, Glut-1 expression, and prognosis in the patients with lung adenocarcinoma and to investigate the role of HIF-1α/HIF-2α in the uptake of FDG in lung adenocarcinoma...
September 23, 2016: Annals of Nuclear Medicine
Jing Liang, Xiaolin Liu, Qi Xie, Guoling Chen, Xingyu Li, Yanrui Jia, Beibei Yin, Xun Qu, Yan Li
OBJECTIVE: To investigate the antitumor effect of endostatin combined with tumor antigen-pulsed dendritic cell (DC)-T cell therapy on lung cancer. METHODS: Transplanted Lewis lung cancer (LLC) models of C57BL/6 mice were established by subcutaneous injection of LLC cells in left extremity axillary. Tumor antigen-pulsed DC-T cells from spleen cells and bone of mice were cultured in vitro. Tumor-bearing mice were randomly divided into three groups, including DC-T+endostatin group, DC-T group, and phosphate-buffered saline (PBS) control group...
August 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Kimberly J Dunham-Snary, Danchen Wu, Edward A Sykes, Amar Thakrar, Leah Rg Parlow, Jeffrey D Mewburn, Joel L Parlow, Stephen L Archer
Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism that is intrinsic to the pulmonary vasculature. Intrapulmonary arteries constrict in response to alveolar hypoxia, diverting blood to better-oxygenated lung segments, thereby optimizing ventilation-perfusion matching and systemic oxygen delivery. In response to alveolar hypoxia, a mitochondrial sensor dynamically changes reactive oxygen species and redox couples in PASMC. This inhibits potassium channels, depolarizes PASMC, activates voltage-gated calcium channels, and increases cytosolic calcium, causing vasoconstriction...
September 16, 2016: Chest
Victoria I Holden, Paul Breen, Sébastien Houle, Charles M Dozois, Michael A Bachman
UNLABELLED: Klebsiella pneumoniae is a Gram-negative pathogen responsible for a wide range of infections, including pneumonia and bacteremia, and is rapidly acquiring antibiotic resistance. K. pneumoniae requires secretion of siderophores, low-molecular-weight, high-affinity iron chelators, for bacterial replication and full virulence. The specific combination of siderophores secreted by K. pneumoniae during infection can impact tissue localization, systemic dissemination, and host survival...
2016: MBio
Shuo Wang, Heng Zeng, Xue-Jiao Xie, Yong-Kang Tao, Xiaochen He, Richard J Roman, Judy L Aschner, Jian-Xiong Chen
Pulmonary arterial hypertension (PAH) is a leading cause of heart failure. Although pulmonary endothelial dysfunction plays a crucial role in the progression of the PAH, the underlying mechanisms are poorly understood. The HIF-α hydroxylase system is a key player in the regulation of vascular remodeling. Knockout of HIF-2α has been reported to cause pulmonary hypertension. The present study examined the role of endothelial cell specific prolyl hydroxylase-2 (PHD2) in the development of PAH and pulmonary vascular remodeling...
August 24, 2016: Oncotarget
Chuanzhao Zhang, Wanqing Iris Zhi, Haiquan Lu, Debangshu Samanta, Ivan Chen, Edward Gabrielson, Gregg L Semenza
Exposure of breast cancer cells to hypoxia increases the percentage of breast cancer stem cells (BCSCs), which are required for tumor initiation and metastasis, and this response is dependent on the activity of hypoxia-inducible factors (HIFs). We previously reported that exposure of breast cancer cells to hypoxia induces the ALKBH5-mediated demethylation of N6-methyladenosine (m6A) in NANOG mRNA leading to increased expression of NANOG, which is a pluripotency factor that promotes BCSC specification. Here we report that exposure of breast cancer cells to hypoxia also induces ZNF217-dependent inhibition of m6A methylation of mRNAs encoding NANOG and KLF4, which is another pluripotency factor that mediates BCSC specification...
August 31, 2016: Oncotarget
Christian Heim, Benjamin Motsch, Sabina Jalilova, Wanja Bernhard, Martina Ramsperger-Gleixner, Nicolai Burzlaff, Michael Weyand, Kai-Uwe Eckardt, Stephan M Ensminger
BACKGROUND: Obliterative bronchiolitis (OB) is the major limiting factor for long-term survival after lung transplantation. As previously shown, donor treatment with a PHD-inhibitor activating hypoxia-inducible transcription factors (HIFs) prevents graft injury both in an allogenic kidney and aortic allograft transplant model. The aim of this study was to investigate the effect of HIF activation with a PHD-inhibitor on the development of OB. METHODS: Fully MHC-mismatched C57BL/6 (H-2(b)) donor tracheas were orthotopically transplanted into CBA/J (H-2(k)) recipients...
August 30, 2016: Transplant Immunology
Rui Guo, Bin Lin, Jing Fei Pan, Emily C Liong, Ai Min Xu, Moussa Youdim, Man Lung Fung, Kwok Fai So, George L Tipoe
Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy...
2016: Scientific Reports
Chen Li, Yu Zhou, Anastacia Loberg, Stanley M Tahara, Punam Malik, Vijay K Kalra
Previous studies showed higher levels of placenta growth factor (PlGF) correlated with increased plasma levels of endothelin-1 (ET-1), a potent vasoconstrictor, in sickle cell disease (SCD). PlGF mediated transcription of ET-1 occurred by activation of HIF-1α, and post-transcriptionally by miR-199a2, which targets the 3' -UTR of HIF-1α mRNA. However, relatively less is known how PlGF represses the expression of miR-199a2 located in the DNM3os transcription unit. Here we show PlGF induces the expression of ATF3, which in association with accessory proteins (JDP2, ATF2 and HDAC6), as determined by proteomic analysis, bind to the DNM3os promoter...
August 29, 2016: Molecular and Cellular Biology
Elizabeth J Campbell, Margreet C M Vissers, Christina Wohlrab, Kevin O Hicks, R Matthew Strother, Stephanie M Bozonet, Bridget A Robinson, Gabi U Dachs
Despite recent evidence for an anti-tumour role for high-dose ascorbate, potential mechanisms of action are still unclear. At mM concentrations that are achieved with high-dose intravenous administration, autoxidation of ascorbate can generate cytotoxic levels of H2O2. Ascorbate is also a required co-factor for the hydroxylases that suppress the transcription factor hypoxia-inducible factor (HIF-1). HIF-1 supports an aggressive tumour phenotype and is associated with poor prognosis, and previous studies have shown that optimizing intracellular ascorbate levels down-regulates HIF-1 activation...
August 24, 2016: Free Radical Biology & Medicine
Alberto Grandi, Alice Santi, Susanna Campagnoli, Matteo Parri, Elisa De Camilli, Chaojun Song, Boquan Jin, Aurelien Lacombe, Serenella Castori-Eppenberger, Paolo Sarmientos, Guido Grandi, Giuseppe Viale, Luigi Terracciano, Paola Chiarugi, Piero Pileri, Renata Grifantini
Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are highly activated in cancer and involved in tumorigenesis and resistance to anti-cancer therapy. UPR is becoming a promising target of anti-cancer therapies. Thus, the identification of UPR components that are highly expressed in cancer could offer new therapeutic opportunity.In this study, we demonstrate that Endoplasmic Reticulum Metallo Protease 1 (ERMP1) is broadly expressed in a high percentage of breast, colo-rectal, lung, and ovary cancers, regardless of their stage and grade...
August 23, 2016: Oncotarget
Cheng-Cheng Wang, Jia-Rui Yuan, Chun-Fei Wang, Nan Yang, Juan Chen, Dan Liu, Jie Song, Liang Feng, Xiao-Bin Tan, Xiao-Bin Jia
BACKGROUND: Phyllanthus emblica L (PEL), a well-known medical plant, has been used in Asian countries for a long time. Increasing evidence suggests that it can prevent the tumorigenesis of cancer associated with nonresolving inflammation. However, the possible anti-inflammatory mechanism responsible for preventing tumorigenesis of precancerous lung lesions is not well elucidated. MATERIALS AND METHODS: Male A/J mice were randomly divided into 5 groups with 10 mice in each group: (1) blank group (saline), (2) benzo(a)pyrene [B(a)P] group, (3) and (4) B(a)P + PEL (5 g/kg/d, 10 g/kg/d, administered by gavage), (5) B(a)P + celecoxib (30 mg/kg/d, administered by gavage)...
August 24, 2016: Integrative Cancer Therapies
Yasuyuki Ikezawa, Jun Sakakibara-Konishi, Hidenori Mizugaki, Satoshi Oizumi, Masaharu Nishimura
BACKGROUND: The Notch receptor plays an important role in various cell fate decisions during development and in cancer. We have previously reported that Notch3 is upregulated by radiation in non-small cell lung cancer (NSCLC) cell lines and that the Notch pathway inhibitor γ secretase inhibitor GSI (gamma-secretase inhibitor), when combined with radiation therapy, significantly suppressed the growth of lung cancer cells. However, little is known about the mechanism of Notch upregulation induced by radiation...
August 23, 2016: International Journal of Clinical Oncology
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