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https://www.readbyqxmd.com/read/27922079/proteomic-profiling-reveals-that-collismycin-a-is-an-iron-chelator
#1
Makoto Kawatani, Makoto Muroi, Akira Wada, Gyo Inoue, Yushi Futamura, Harumi Aono, Kenshirou Shimizu, Takeshi Shimizu, Yasuhiro Igarashi, Naoko Takahashi-Ando, Hiroyuki Osada
Collismycin A (CMA), a microbial product, has anti-proliferative activity against cancer cells, but the mechanism of its action remains unknown. Here, we report the identification of the molecular target of CMA by ChemProteoBase, a proteome-based approach for drug target identification. ChemProteoBase profiling showed that CMA is closely clustered with di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone, an iron chelator. CMA bound to both Fe(II) and Fe(III) ions and formed a 2:1 chelator-iron complex with a redox-inactive center...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921309/hypoxia-inducible-factor-1%C3%AE-induced-interleukin-33-expression-in-intestinal-epithelia-contributes-to-mucosal-homeostasis-in-inflammatory-bowel-disease
#2
M Sun, C He, W Wu, G Zhou, F Liu, Y Cong, Z Liu
Intestinal epithelial cells (IECs), an important barrier to gut microbiota, are subject to low oxygen tension, particularly during intestinal inflammation. Hypoxia inducible factor-1α (HIF-1α) is expressed highly in the inflamed mucosa of inflammatory bowel disease (IBD) and functions as a key regulator in maintenance of intestinal homeostasis. However, how IEC-derived HIF-1α regulates intestinal immune responses in IBD is still not understood completely. We report here that the expression of HIF-1α and IL-33 was increased significantly in the inflamed mucosa of IBD patients as well as mice with colitis induced by dextran sulphate sodium (DSS)...
November 7, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27920521/celastrol-nanomicelles-attenuate-cytokine-secretion-in-macrophages-and-inhibit-macrophage-induced-corneal-neovascularization-in-rats
#3
Zhanrong Li, Jingguo Li, Lei Zhu, Ying Zhang, Junjie Zhang, Lin Yao, Dan Liang, Liya Wang
The aim of the present study was to investigate the inhibitory effects of celastrol-loaded nanomicelles (CNMs) on activated macrophage-induced corneal neovascularization (CNV) in rats and cytokine secretion in macrophages. Using an angiogenesis assay in vitro, we detected the effects of CNMs on human umbilical vein endothelial cell (HUVEC) migration and invasion. In addition, the expression levels of cytokines secreted from hypoxia-induced macrophages were assessed through cytokine array analysis. The expression of hypoxia-inducible factors-1α (HIF-1α), nuclear factor-kappa B p65 (NF-κB p65), phospho-nuclear factor-kappa B p65 (phospho-NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), phospho-p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-ERK1/2 was analyzed by western blotting...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27919930/mir-17-20-controls-prolyl-hydroxylase-2-phd2-hypoxia-inducible-factor-1-hif1-to-regulate-pulmonary-artery-smooth-muscle-cell-proliferation
#4
Tianji Chen, Qiyuan Zhou, Haiyang Tang, Melike Bozkanat, Jason X-J Yuan, J Usha Raj, Guofei Zhou
BACKGROUND: Previously we found that smooth muscle cell (SMC)-specific knockout of miR-17~92 attenuates hypoxia-induced pulmonary hypertension. However, the mechanism underlying miR-17~92-mediated pulmonary artery SMC (PASMC) proliferation remains unclear. We sought to investigate whether miR-17~92 regulates hypoxia-inducible factor (HIF) activity and PASMC proliferation via prolyl hydroxylases (PHDs). METHODS AND RESULTS: We show that hypoxic sm-17~92(-/-) mice have decreased hematocrit, red blood cell counts, and hemoglobin contents...
December 5, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27919191/phytotherapeutic-approach-a-new-hope-for-polycyclic-aromatic-hydrocarbons-induced-cellular-disorders-autophagic-and-apoptotic-cell-death
#5
Durgesh Nandini Das, Prashanta Kumar Panda, Prajna Paramita Naik, Subhadip Mukhopadhyay, Niharika Sinha, Sujit K Bhutia
Polycyclic aromatic hydrocarbons (PAHs) comprise the major class of cancer-causing chemicals and are ranked ninth among the chemical compounds threatening to humans. Moreover, interest in PAHs has been mainly due to their carcinogenic property, these compounds are genotoxic, teratogenic, mutagenic, and carcinogenic. Polymorphism in cytochrome P450 (CYP450) and aryl hydrocarbon receptor (AhR) have the capacity to convert procarcinogens into carcinogens, which is an imperative factor contributing to individual susceptibility to cancer development...
December 5, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27918992/investigation-of-the-metabolites-of-the-hif-stabilizer-fg-4592-roxadustat-in-five-different-in-vitro-models-and-in-a-human-doping-control-sample-using-high-resolution-mass-spectrometry
#6
Annelie Hansson, Mario Thevis, Holly Cox, Geoff Miller, Daniel Eichner, Ulf Bondesson, Mikael Hedeland
FG-4592 is a hypoxia-inducible factor (HIF) stabilizer, which can increase the number of red blood cells in the body. It has not been approved by regulatory authorities, but is available for purchase on the Internet. Due to its ability to improve the oxygen transportation mechanism in the body, FG-4592 is of interest for doping control laboratories, but prior to this study, little information about its metabolism was available. In this study, the metabolism of FG-4592 was investigated in a human doping control sample and in five in vitro models: human hepatocytes and liver microsomes, equine liver microsomes and S9 fraction and the fungus Cunninghamella elegans...
November 27, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27918956/the-injury-of-fine-particulate-matter-from-cooking-oil-fumes-on-umbilical-cord-blood-vessels-in-vitro
#7
Lijuan Hou, Jian Zhang, Chao Zhang, Yachun Xu, Xiaoxia Zhu, Cijiang Yao, Ying Liu, Tao Li, Jiyu Cao
Cooking oil fumes (COFs) derived PM2.5 is the major source of indoor air pollution in Asia. For this, a pregnant rat model within different doses of cooking oil fumes (COFs) derived PM2.5 was established in pregnancy in our research. Our previous studies have showed that exposure to COFs-derived PM2.5 was related to adverse pregnancy outcomes. However, the mechanisms of signaling pathways remain unknown. Therefore, this study aimed to investigate the underlying mechanisms induced by COFs-derived PM2.5 injury on umbilical cord blood vessels (UCs) in vitro...
November 21, 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27918936/promoting-angiogenesis-with-mesoporous-microcarriers-through-a-synergistic-action-of-delivered-silicon-ion-and-vegf
#8
Khandmaa Dashnyam, Guang-Zhen Jin, Joong-Hyun Kim, Roman Perez, Jun-Hyeog Jang, Hae-Won Kim
Angiogenic capacity of biomaterials is a key asset to drive vascular ingrowth during tissue repair and regeneration. Here we design a unique angiogenic microcarrier based on sol-gel derived mesoporous silica. The microspheres offer a potential angiogenic stimulator, Si ion, 'intrinsically' within the chemical structure. Furthermore, the highly mesoporous nature allows the loading and release of angiogenic growth factor 'extrinsically'. The Si ion is released from the microcarriers at therapeutic ranges (over a few ppm per day), which indeed up-regulates the expression of hypoxia inducing factor 1α (HIF1α) and stabilizes it by blocking HIF-prolyl hydroxylase 2 (PHD2) in HUVECs...
November 28, 2016: Biomaterials
https://www.readbyqxmd.com/read/27918469/dietary-compound-chrysin-inhibits-retinal-neovascularization-with-abnormal-capillaries-in-db-db-mice
#9
Min-Kyung Kang, Sin-Hye Park, Yun-Ho Kim, Eun-Jung Lee, Lucia Dwi Antika, Dong Yeon Kim, Yean-Jung Choi, Young-Hee Kang
Diabetic retinopathy (DR) develops in a significant proportion of patients with chronic diabetes, characterized by retinal macular edema and abnormal retinal vessel outgrowth leading to vision loss. Chrysin, a naturally-occurring flavonoid found in herb and honeycomb, has anti-inflammatory, antioxidant, and anti-cancer properties. This study sought to determine the protective effects of chrysin on retinal neovascularization with abnormal vessels and blood-retinal barrier (BRB) breakdown in 33 mM glucose-exposed human retinal endothelial cells and in db/db mouse eyes...
December 3, 2016: Nutrients
https://www.readbyqxmd.com/read/27918235/comprehensive-mapping-of-5-hydroxymethylcytosine-epigenetic-dynamics-in-axon-regeneration
#10
Yong-Hwee Eddie Loh, Andrew Koemeter-Cox, Mattéa Finelli, Li Shen, Roland H Friedel, Hongyan Zou
In contrast to central nervous system neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated in DRG neurons, along with increased 5-hydroxymethylcytosine (5 hmC). We generated genome-wide 5 hmC maps in adult DRG, which revealed that peripheral and central axotomy (leading to no regenerative effect) triggered differential 5 hmC changes that are associated with distinct signaling pathways...
December 5, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27918097/sugars-and-fat-a-healthy-way-to-generate-functional-regulatory-t-cells
#11
Sarah Sharon Gabriel, Axel Kallies
Cellular metabolism has emerged as an important regulator of adaptive immunity. While the metabolic requirements of conventional T cells are increasingly understood, the role of cellular metabolism in Foxp3(+) regulatory T (Treg) cells is less clear. Although it is well accepted that repression of Akt/mTOR, HIF-1α and aerobic glycolysis are important for the efficient generation of Treg cells in vitro, clear evidence how these pathways impact on Treg-cell development in vivo is limited. Furthermore, newer studies have shown that the same pathways that appear to suppress Treg-cell development are active in and required for functionally mature Treg cells...
December 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27916987/weight-loss-induced-cellular-stress-in-subcutaneous-adipose-tissue-and-the-risk-for-weight-regain-in-overweight-and-obese-adults
#12
N J T Roumans, R G Vink, F G Bouwman, P Fazelzadeh, M A van Baak, E C M Mariman
BACKGROUND/OBJECTIVE: Weight loss is often followed by weight regain after the dietary intervention (DI). Cellular stress is increased in adipose tissue of obese individuals. However, the relation between cellular stress and weight regain is unclear. Previously, we observed increased adipose tissue cellular stress of participants regaining weight compared to participants maintaining weight loss. In the current study, we further investigated the relation between weight regain and changes in the expression of stress-related genes and stress protein levels to determine possible predictors of weight regain...
December 5, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27915020/multifunctions-of-dual-zn-mg-ion-co-implanted-titanium-on-osteogenesis-angiogenesis-and-bacteria-inhibition-for-dental-implants
#13
Yiqiang Yu, Guodong Jin, Yang Xue, Donghui Wang, Xuanyong Liu, Jiao Sun
In order to improve the osseointegration and long-term survival of dental implants, it is urgent to develop a multifunctional titanium surface which would simultaneously have osteogeneic, angiogeneic and antibacterial properties. In this study, a potential dental implant material-dual Zn/Mg ion co-implanted titanium (Zn/Mg-PIII) was developed via plasma immersion ion implantation (PIII). The Zn/Mg-PIII surfaces were found to promote initial adhesion and spreading of rat bone marrow mesenchymal stem cells (rBMSCs) via the upregulation of the gene expression of integrin α1 and integrin β1...
November 30, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27913198/argininosuccinate-synthetase-1-ass1-is-a-common-metabolic-marker-of-chemosensitivity-for-targeted-arginine-and-glutamine-starvation-therapy
#14
Yan Long, Wen-Bin Tsai, Dajuan Wang, David H Hawke, Niramol Savaraj, Lynn G Feun, Mien-Chie Hung, Helen H W Chen, Macus Tien Kuo
Argininosuccinate synthetase 1 (ASS1) is the rate-limiting enzyme that catalyzes the biosynthesis of arginine (Arg). Many malignant human tumors are auxotrophic for Arg because ASS1 is silenced. ASS1 has been established as a sensor of Arg auxotrophic response and a chemosensitivity marker for Arg starvation therapy. Here, we report that ASS1 is also a sensor for glutamine (Gln)-deprivation response, and that upregulation of ASS1 expression is associated with resistance to Gln-starvation treatments. Knockdown of ASS1 expression resulted in increased sensitivity to both Arg- and Gln-starvation, whereas increased ASS1 expression by ectopic transfection is associated with resistance to both Arg- and Gln-starvation...
November 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27911865/mitochondrial-pyruvate-carrier-function-is-negatively-linked-to-warburg-phenotype-in-vitro-and-malignant-features-in-esophageal-squamous-cell-carcinomas
#15
Yaqing Li, Xiaoran Li, Quancheng Kan, Mingzhi Zhang, Xiaoli Li, Ruiping Xu, Junsheng Wang, Dandan Yu, Mariusz Adam Goscinski, Jian-Guo Wen, Jahn M Nesland, Zhenhe Suo
Aerobic glycolysis is one of the emerging hallmarks of cancer cells. In this study, we investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with MPC blocker UK5099 and the metabolic alteration as well as aggressive features of esophageal squamous carcinoma. It was found that blocking pyruvate transportation into mitochondria attenuated mitochondrial oxidative phosphorylation (OXPHOS) and triggered aerobic glycolysis, a feature of Warburg effect. In addition, the HIF-1α expression and ROS production were also activated upon UK5099 application...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911265/mirna-543-promotes-osteosarcoma-cell-proliferation-and-glycolysis-by-partially-suppressing-prmt9-and-stabilizing-hif-1%C3%AE-protein
#16
Heng Zhang, Xiaofeng Guo, Xing Feng, Tingting Wang, Zhaohua Hu, Xiangyong Que, Qingsong Tian, Tianbo Zhu, Guixian Guo, Wei Huang, Xinzhi Li
Osteosarcoma (OS) is the most common primary bone tumor, occurring frequently in adolescents and possessing a high malignant severity. MicroRNAs play critical roles during OS development. Thus, elucidation of the involvement of specific microRNAs in the development of OS may provide novel therapeutic targets for OS treatment. Here, we showed that in the OS specimens from patients, the levels of miR-543 were significantly increased whereas the levels of PRMT9 were significantly decreased, compared to the paired normal bone tissue...
November 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27909871/nap-interferes-with-hypoxia-inducible-factors-and-vegf-expression-in-retina-of-diabetic-rats
#17
Agata Grazia D'Amico, Grazia Maugeri, Claudio Bucolo, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
The retinal microvascular damage is a complication of diabetic retinopathy (DR). Hyperglycemia and hypoxia are responsible of aberrant vessel's proliferation. The cellular response to hypoxia is mediated through activation of hypoxia-inducible factors (HIFs). Among these, HIF-1α modulates expression of its target gene, VEGF, whose upregulation controls the angiogenic event during DR development. In a previous study, we have demonstrated that a small peptide, NAP, is able to protect retina from hyperglycemic insult...
December 1, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27909249/mortalin-mediated-and-erk-controlled-targeting-of-hif-1%C3%AE-to-mitochondria-confers-resistance-to-apoptosis-under-hypoxia
#18
Ilias Mylonis, Maria Kourti, Martina Samiotaki, George Panayotou, George Simos
Hypoxia inducible factor-1 (HIF-1) is the main transcriptional activator of the cellular response to hypoxia and an important target of anticancer therapy. Phosphorylation by ERK stimulates the transcriptional activity of HIF-1α by inhibiting its CRM1-dependent nuclear export. Here, we demonstrate that phosphorylation by ERK also regulates the association of HIF-1α with a novel interaction partner identified as mortalin (GRP75) which mediates non-genomic involvement of HIF-1α in apoptosis. Mortalin binds specifically to HIF-1α lacking modification by ERK and their complex is localized outside the nucleus...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27908264/hypoxia-and-inflammation-in-prostate-cancer-progression-cross-talk-with-androgen-and-estrogen-receptors-and-cancer-stem-cells
#19
Matteo A Russo, Linda Ravenna, Laura Pellegrini, Elisa Petrangeli, Luisa Salvatori, Thea Magrone, Massimo Fini, Marco Tafani
Tumors are complex tissues in which transformed cells communicate with the surrounding microenvironment and evolve traits promoting their own survival and malignancy. Hypoxia and inflammation are constant characteristics of prostate tumor microenvironment influencing both cancer stem cells and differentiated tumor cells. HIFs and NF-kB are the key regulators of the transcriptional response to hypoxic and inflammatory stresses, respectively, and a crosstalk between HIFs and NF-kB pathways has been widely documented...
November 30, 2016: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/27904680/enhancement-of-early-cardiac-differentiation-of-dedifferentiated-fat-cells-by-dimethyloxalylglycine-via-notch-signaling-pathway
#20
Fuhai Li, Zongzhuang Li, Zhi Jiang, Ye Tian, Zhi Wang, Wei Yi, Chenyun Zhang
Background: Hypoxia has been reported to possess the ability to induce mature lipid-filled adipocytes to differentiate into fibroblast-like multipotent dedifferentiated fat (DFAT) cells and stem cells such as iPSCs (interstitial pluripotent stem cells) and ESCs (embryonic stem cells) and then to differentiate into cardiomyocytes. However, the effect of hypoxia on cardiac differentiation of DFAT cells and its underlying molecular mechanism remains to be investigated. Objective: To investigate the role of hypoxia in early cardiac differentiation of DFAT cells and the underlying molecular mechanism...
2016: American Journal of Translational Research
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