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https://www.readbyqxmd.com/read/29666476/hif1a-inactivation-rescues-photoreceptor-degeneration-induced-by-a-chronic-hypoxia-like-stress
#1
Maya Barben, Divya Ail, Federica Storti, Katrin Klee, Christian Schori, Marijana Samardzija, Stylianos Michalakis, Martin Biel, Isabelle Meneau, Frank Blaser, Daniel Barthelmes, Christian Grimm
Reduced choroidal blood flow and tissue changes in the ageing human eye impair oxygen delivery to photoreceptors and the retinal pigment epithelium. As a consequence, mild but chronic hypoxia may develop and disturb cell metabolism, function and ultimately survival, potentially contributing to retinal pathologies such as age-related macular degeneration (AMD). Here, we show that several hypoxia-inducible genes were expressed at higher levels in the aged human retina suggesting increased activity of hypoxia-inducible transcription factors (HIFs) during the physiological ageing process...
April 17, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29653185/sex-differences-in-the-development-of-hepatic-steatosis-in-cafeteria-diet-induced-obesity-in-young-mice
#2
Fabiana Rodrigues Silva Gasparin, Fernando Olinto Carreño, Juliana Moraes Mewes, Eduardo Hideo Gilglioni, Clairce Luzia Salgueiro Pagadigorria, Maria Raquel Marçal Natali, Karina Sayuri Utsunomiya, Rodrigo Polimeni Constantin, Amanda Tomie Ouchida, Carlos Curti, Ingrid C Gaemers, Ronald Petrus Johannes Oude Elferink, Jorgete Constantin, Emy Luiza Ishii-Iwamoto
The present study was planned to improve our understanding about sex differences in the development of hepatic steatosis in cafeteria diet-induced obesity in young mice. Female (FCaf) and male (MCaf) mice fed a cafeteria diet had similar body weight gain and adiposity index, but FCaf had a more extensive steatosis than MCaf. FCaf livers exhibited a higher non-alcoholic fatty liver disease activity score, elevated lipid percentage area (+34%) in Sudan III staining and increased TG content (+25%) compared to MCaf...
April 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29652520/hemolysis-induced-lung-vascular-leakage-contributes-to-the-development-of-pulmonary-hypertension
#3
Olga Rafikova, Elissa R Williams, Matthew L McBride, Marina Zemskova, Anup Srivastava, Vineet Nair, Ankit A Desai, Paul R Langlais, Evgeny Zemskov, Marc Simon, Lawrence J Mandarino, Ruslan Rafikov
RATIONALE: While hemolytic anemia-associated pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are more common than the prevalence of idiopathic PAH alone, the role of hemolysis in the development of PAH is poorly characterized. OBJECTIVES: We hypothesized that hemolysis independently contributes to PAH pathogenesis via endothelial barrier dysfunction with resulting perivascular edema and inflammation. METHODS: Plasma samples from patients with and without PAH (both confirmed by right heart catheterization) were used to measure free hemoglobin (Hb) and its correlation with PAH severity...
April 13, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29626523/expression-of-genes-in-primo-vasculature-floating-in-lymphatic-endothelium-under-lipopolysaccharide-and-acupuncture-electric-stimulation
#4
Jun-Young Shin, Jong-Ok Ji, Da-Woon Choi, Sang-Heon Choi, Jong-Gu Choi, Min-Suk Rho, Ji Yoon Lee, Sang-Suk Lee
It is known that the existence of primo vascular system (PVS) including the primo nodes and vessels. However, it is poorly understood the relevant genes in the PVS system both patho- and physiologic condition. Here, we first examined the gene expression in primo vessels (PV) floating in lymphatic endothelium by isolation of PVS and lymphatic vessels (LV) containing PVS. To investigate therapeutic effects, both PV and LV containing PVS were isolated after lipopolysaccharides (LPS) injection and acupuncture electric stimulation (AES) at two acupoints of Joksamni (ST36) and Hapgok (LI04) following LPS...
April 4, 2018: Journal of Acupuncture and Meridian Studies
https://www.readbyqxmd.com/read/29625581/evaluation-of-the-effects-of-ascorbic-acid-on-metabolism-of-human-mesenchymal-stem-cells
#5
Koichi Fujisawa, Kazusa Hara, Taro Takami, Sae Okada, Toshihiko Matsumoto, Naoki Yamamoto, Isao Sakaida
BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells holding much promise for applications in regenerative medicine. However, with problems such as aging, increases in heteroploid cells, genomic instability, and reduced maintenance of stemness, more stable culturing methods and the production of MSCs with an improved therapeutic effect are desired. Ascorbic acid (AsA), which is a cofactor for a variety of enzymes and has an antioxidant effect, cannot be synthesized by certain animals, including humans...
April 6, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29601782/hepatic-phd2-hif-1%C3%AE-axis-is-involved-in-postexercise-systemic-energy-homeostasis
#6
Beibei Luo, Dao Xiang, Die Wu, Changcheng Liu, Yiqun Fang, Peijie Chen, Yi-Ping Hu
Exercise plays an important role in the prevention and treatment of chronic liver disease and associated metabolic disorders. A single bout of exercise induces tissue blood flow redistribution, which decreases splanchnic circulation and leads to physiologic hypoxia in the gastrointestinal system and liver. The transcription factor, hypoxia inducible factor-1α (HIF-1α), and its regulator, prolylhydroxylase 2 (PHD2), play pivotal roles in the response to oxygen flux by regulating downstream gene expression levels in the liver...
March 30, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29587528/diet-dependent-changes-in-the-intestinal-dna-methylome-after-introduction-of-enteral-feeding-in-preterm-pigs
#7
Xiaoyu Pan, Desheng Gong, Fei Gao, Per Torp Sangild
AIM: To examine how enteral feeding affects the intestinal epigenome and gene expression just after preterm birth. MATERIALS & METHODS: Intestinal tissue from preterm pigs, modeling preterm infants, was collected at birth and 5 days after gradual introduction of infant formula or bovine colostrum. The intestinal tissue was analyzed by reduced representation bisulfite sequencing and real-time qPCR. RESULTS: Relative to colostrum, formula increased bacterial epithelial adherence and LBP (lipopolysaccharide binding protein) expression, which was regulated by promoter methylation...
March 28, 2018: Epigenomics
https://www.readbyqxmd.com/read/29568350/eif3c-enhanced-exosome-secretion-promotes-angiogenesis-and-tumorigenesis-of-human-hepatocellular-carcinoma
#8
Hsin-Yi Lee, Chi-Kuan Chen, Chun-Ming Ho, Szu-Shuo Lee, Chieh-Yu Chang, Kuan-Ju Chen, Yuh-Shan Jou
Targeting tumor angiogenesis is a common strategy against human hepatocellular carcinoma (HCC). However, identification of molecular targets as biomarker for elevating therapeutic efficacy is critical to prolong HCC patient survival. Here, we showed that EIF3C (eukaryotic translation initiation factor 3 subunit C) is upregulated during HCC tumor progression and associated with poor patient survival. Expression of EIF3C did not alter proliferation and expression of other tumor progressive genes such as HIF1A, TGFβ1 and VEGF, but reduced cell migration in HCC cells...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29552196/curcumin-may-serve-an-anticancer-role-in-human-osteosarcoma-cell-line-u-2-os-by-targeting-itpr1
#9
Zhanpeng Luo, Dawei Li, Xiaobo Luo, Litao Li, Suxi Gu, Long Yu, Yuanzheng Ma
The present study aimed to determine the mechanisms of action of curcumin in osteosarcoma. Human osteosarcoma U-2 OS cells was purchased from the Cell Bank of the Chinese Academy of Sciences. RNA sequencing analysis was performed for 2 curcumin-treated samples and 2 control samples using Illumina deep sequencing technology. The differentially expressed genes were identified using Cufflink software. Enrichment and protein-protein interaction network analyses were performed separately using cluster Profiler package and Cytoscape software to identify key genes...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29552123/expression-profiling-analysis-of-autophagy-related-genes-in-perineural-invasion-of-cutaneous-squamous-cell-carcinoma
#10
Li-Qiang Zheng, Shan-Yi Li, Cheng-Xin Li
The aim of the present study was to identify the potential autophagy-related genes and to explore the underlying molecular mechanisms involved in cutaneous squamous cell carcinoma of head and neck (cSCCHN) by bioinformatics analysis. The Gene Expression Omnibus (GEO) series GSE86544 was downloaded from the GEO database. The primary data was generated from cSCCHN with clinical perineural invasion (PNI) and cSCCHN without PNI, and was further analyzed in order to identify differentially expressed genes (DEGs)...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29535421/astrocyte-derived-ccl20-reinforces-hif-1-mediated-hypoxic-responses-in-glioblastoma-by-stimulating-the-ccr6-nf-%C3%AE%C2%BAb-signaling-pathway
#11
Peng Jin, Seung-Hyun Shin, Yang-Sook Chun, Hyun-Woo Shin, Yong Jae Shin, Yeri Lee, Donggeon Kim, Do-Hyun Nam, Jong-Wan Park
During tumor development, stromal cells are co-opted to the tumor milieu and provide favorable conditions for the tumor. Hypoxia stimulates cancer cells to acquire a more malignant phenotype via activation of hypoxia-inducible factor 1 (HIF-1). Given that cancer cells and astrocytes in glioblastomas coexist in a hypoxic microenvironment, we examined whether astrocytes affect the adaptation of glioblastoma cells to hypoxia. Immunoblotting, reporter assays, quantitative RT-PCR, and chromatin immunoprecipitation were performed to evaluate HIF-1 signaling in glioblastoma cells...
March 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29514656/targeting-hif1a-rescues-cone-degeneration-and-prevents-subretinal-neovascularization-in-a-model-of-chronic-hypoxia
#12
Maya Barben, Christian Schori, Marijana Samardzija, Christian Grimm
BACKGROUND: Degeneration of cone photoreceptors leads to loss of vision in patients suffering from age-related macular degeneration (AMD) and other cone dystrophies. Evidence, such as choroidal ischemia and decreased choroidal blood flow, implicates reduced tissue oxygenation in AMD pathology and suggests a role of the cellular response to hypoxia in disease onset and progression. Such a chronic hypoxic situation may promote several cellular responses including stabilization of hypoxia-inducible factors (HIFs)...
March 7, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29511172/rb-is-required-for-retinal-angiogenesis-and-lamination
#13
Yi Zhou, Ran Wei, Liu Zhang, Yongjiang Chen, Suying Lu, Chen Liang, Yujiao Wang, Lirong Xiao, Junjun Zhang, Rod Bremner, Danian Chen
Retinoblastoma tumor suppressor (Rb) promotes cell cycle exit, survival, differentiation, and tumor suppression in the retina. Here, we show it is also essential for vascularization and lamination. Despite minimal effects on Hif1a target expression, intraretinal vascular plexi did not form in the Rb-/- murine retina. Deleting adenovirus E2 promoter binding factor 3 (E2f3), which rescues starburst amacrine cell differentiation, or E2f2, had no effect, but deleting E2f1, which promotes neuronal cell cycle exit and survival, restored retinal vasculature...
March 6, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29483579/hypoxia-inducible-factor-2-alpha-dependent-induction-of-amphiregulin-dampens-myocardial-ischemia-reperfusion-injury
#14
Michael Koeppen, Jae W Lee, Seong-Wook Seo, Kelley S Brodsky, Simone Kreth, Ivana V Yang, Peter M Buttrick, Tobias Eckle, Holger K Eltzschig
Myocardial ischemia-reperfusion injury (IRI) leads to the stabilization of the transcription factors hypoxia-inducible factor 1-alpha (HIF1-alpha) and hypoxia-inducible factor 2-alpha (HIF2-alpha). While previous studies implicate HIF1-alpha in cardioprotection, the role of HIF2-alpha remains elusive. Here we show that HIF2-alpha induces the epithelial growth factor amphiregulin (AREG) to elicit cardioprotection in myocardial IRI. Comparing mice with inducible deletion of Hif1a or Hif2a in cardiac myocytes, we show that loss of Hif2-alpha increases infarct sizes...
February 26, 2018: Nature Communications
https://www.readbyqxmd.com/read/29460267/hypoxia-preconditioned-human-umbilical-vein-endothelial-cells-protect-against-neurovascular-damage-after-hypoxic-ischemia-in-neonatal-brain
#15
Yi-Chao Lee, Ying-Chao Chang, Chia-Ching Wu, Chao-Ching Huang
Therapy targeting the neurovascular unit may provide effective neuroprotection against neonatal hypoxia-ischemia (HI). We hypothesized that the peripheral injection of hypoxia-preconditioned human umbilical vein endothelial cells (HUVECs) following HI protects against neurovascular damage and provides long-term neuroprotection in a postpartum (P) day-7 rat pup model. Compared with normoxic HUVECs, hypoxic HUVECs showed enhanced migration and angiogenesis in vitro and had augmented migration effects into the brain when administered intraperitoneally in vivo after HI...
February 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29456535/liver-x-receptor-agonist-therapy-prevents-diffuse-alveolar-hemorrhage-in-murine-lupus-by-repolarizing-macrophages
#16
Shuhong Han, Haoyang Zhuang, Stepan Shumyak, Jingfan Wu, Chao Xie, Hui Li, Li-Jun Yang, Westley H Reeves
The generation of CD138+ phagocytic macrophages with an alternative (M2) phenotype that clear apoptotic cells from tissues is defective in lupus. Liver X receptor-alpha (LXRα) is an oxysterol-regulated transcription factor that promotes reverse cholesterol transport and alternative (M2) macrophage activation. Conversely, hypoxia-inducible factor 1-α (HIF1α) promotes classical (M1) macrophage activation. The objective of this study was to see if lupus can be treated by enhancing the generation of M2-like macrophages using LXR agonists...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29449623/targeted-disruption-of-the-inos-gene-improves-adipose-tissue-inflammation-and-fibrosis-in-leptin-deficient-ob-ob-mice-role-of-tenascin-c
#17
S Becerril, A Rodríguez, V Catalán, L Méndez-Giménez, B Ramírez, N Sáinz, M Llorente, X Unamuno, J Gómez-Ambrosi, G Frühbeck
BACKGROUND/OBJECTIVES: Obesity is related to a dynamic extracellular matrix (ECM) remodeling, which involves the synthesis and degradation of different proteins, such as tenascin C (TNC) in the adipose tissue (AT). Given the functional relationship between leptin and inducible nitric oxide synthase (iNOS), our aim was to analyze the impact of the absence of the iNOS gene in AT inflammation and ECM remodeling in ob/ob mice. SUBJECTS/METHODS: The expression of genes involved in inflammation and ECM remodeling was evaluated in 10-week-old male double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes as well as in ob/ob mice classified into three groups [control, leptin-treated (1 mg kg -1 day -1 ) and pair-fed]...
February 15, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29447016/tgf-b1-or-hypoxia-enhance-glucose-metabolism-and-lactate-production-via-hif1a-signaling-in-tendon-cells
#18
Katie J Sikes, Jun Li, Shu-Guang Gao, Quan Shen, John D Sandy, Anna Plaas, Vincent M Wang
Healthy tendons are maintained in homeostasis through controlled usage of glucose for energy and redox equilibrium. Tendon cell stress imposed by overuse injury or vascular insufficiency is accompanied by activation of wound healing pathways which facilitate an adaptive response and the restoration of homeostasis. To understand this response at the gene expression level we have studied the in vivo effects of injected TGF-β1 in a murine model of tendinopathy, as well as treatment of murine tendon explants with either TGF-β1 or hypoxia in vitro...
February 15, 2018: Connective Tissue Research
https://www.readbyqxmd.com/read/29438518/obesity-and-high-fat-diet-induce-distinct-changes-in-placental-gene-expression-and-pregnancy-outcome
#19
Erica B Mahany, Xingfa Han, Beatriz C Borges, Sanseray da Silveira Cruz-Machado, Susan J Allen, David Garcia-Galiano, Mark J Hoenerhoff, Nicole H Bellefontaine, Carol F Elias
Obese women are at high risk of pregnancy complications, including preeclampsia, miscarriage, preterm birth, stillbirth and neonatal death. In the present study, we aimed to determine the effects of obesity on pregnancy outcome and placental gene expression in preclinical mouse models of genetic and nutritional obesity. The leptin receptor null reactivatable (LepRloxTB), the LepR deficient (Leprdb/+) and high fat diet (HFD) fed mice were assessed for fertility, pregnancy outcome, placental morphology and placental transcriptome using standard qPCR and qPCR arrays...
February 9, 2018: Endocrinology
https://www.readbyqxmd.com/read/29409830/hif1-alpha-regulates-acinar-cell-function-and-response-to-injury-in-mouse-pancreas
#20
Min-Jung Park, Sapna Iyer, Xiang Xue, Juliana Bragazzi Cunha, Shufang Gu, David Moons, Steven W Pipe, John A Williams, Diane M Simeone, Yatrik M Shah, M Bishr Omary
We investigated whether intra-pancreatic coagulation, with deposition of the fibrinogen-γ dimer (Fib-γD) and hypoxia, affect the severity of acute pancreatitis (AP) in mice. Pancreata of mice with AP induced by administration of cerulein or by L-arginine, or from patients with AP, had increased deposition of Fib-γD compared to control pancreata. Heparin administration protected mice from cerulein-induced AP and prevented Fib-γD formation. Cerulein administration resulted in activation and stabilization of HIF1-alpha in pancreata of ODD-luc HIF1-alpha reporter mice...
January 31, 2018: Gastroenterology
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