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https://www.readbyqxmd.com/read/28538980/downregulation-of-lysyl-oxidase-protects-retinal-endothelial-cells-from-high-glucose-induced-apoptosis
#1
Dongjoon Kim, Robert P Mecham, Philip C Trackman, Sayon Roy
Purpose: To investigate the effect of reducing high glucose (HG)-induced lysyl oxidase (LOX) overexpression and increased activity on retinal endothelial cell apoptosis. Methods: Rat retinal endothelial cells (RRECs) were grown in normal (N) or HG (30 mM glucose) medium for 7 days. In parallel, RRECs were grown in HG medium and transfected with LOX small interfering RNA (siRNA), scrambled siRNA as control, or exposed to β-aminopropionitrile (BAPN), a LOX inhibitor...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28537923/aldehyde-dehydrogenase-1a1-increases-nadh-levels-and-promotes-tumor-growth-via-glutathione-dihydrolipoic-acid-dependent-nad-reduction
#2
Baiyun Wang, Xue Chen, Zixi Wang, Wei Xiong, Tao Xu, Xinyuan Zhao, Yang Cao, Yanru Guo, Lin Li, She Chen, Song Huang, Xiaodong Wang, Min Fang, Zhirong Shen
Aldehyde dehydrogenase 1A1 (ALDH1A1) is a member of the aldehyde dehydrogenase superfamily that oxidizes aldehydes to their corresponding acids, reactions that are coupled to the reduction of NAD+ to NADH. We report here that ALDH1A1 can also use glutathione (GSH) and dihydrolipoic acid (DHLA) as electron donors to reduce NAD+ to NADH. The GSH/DHLA-dependent NAD+-reduction activity of ALDH1A1 is not affected by the aldehyde dehydrogenase inhibitor or by mutation of the residues in its aldehyde-binding pocket...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28535607/generation-of-the-new-discovered-resistant-gene-mcr-1-knockout-in-escherichia-coli-using-crispr-cas9-system
#3
Lichang Sun, Tao He, Lili Zhang, Maoda Pang, Qiaoyan Zhang, Yan Zhou, Hongduo Bao, Ran Wang
The mcr-1 gene was the new discovered "superbug" gene which makes the bacteria highly resistant to the last-resort class of antibiotics in China in 2016. The mcr-1 gene raised serious concern about its possible global dissemination and spread. Here, we report a potential anti-resistant strategy that CRISPR/Cas9 mediated approach can efficiently induce mcr-1 gene knockout in Escherichia coli. Our findings suggested that using CRISPPR/Cas9 system to knockout the resistant gene mcr-1 might be a potential anti-resistant strategy...
May 24, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28535426/new-role-of-pcsk9-in-atherosclerotic-inflammation-promotion-involving-the-tlr4-nf-%C3%AE%C2%BAb-pathway
#4
Zhi-Han Tang, Juan Peng, Zhong Ren, Jing Yang, Ting-Ting Li, Tao-Hua Li, Zuo Wang, Dang-Heng Wei, Lu-Shan Liu, Xi-Long Zheng, Zhi-Sheng Jiang
BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin 9 (PCSK9) has emerged as a popular target in the development of new cholesterol-lowering drugs and therapeutic interventions for atherosclerosis. PCSK9 could accelerate atherosclerosis through mechanisms beyond the degradation of the hepatic low-density lipoprotein receptor. Several clinical studies suggested that PCSK9 is involved in atherosclerotic inflammation. Accordingly, this study aimed to explore the role of PCSK9 in vascular inflammation that promotes atherosclerotic progression...
April 29, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28535417/ezrin-nf-kb-activation-regulates-epithelial-mesenchymal-transition-induced-by-egf-and-promotes-metastasis-of-colorectal-cancer
#5
Yingru Li, Zhaoyu Lin, Bin Chen, Shuang Chen, Zhipeng Jiang, Taicheng Zhou, Zehui Hou, Youyuan Wang
There is growing evidence that epithelial mesenchymal-transition (EMT) plays significant roles in terms of tumor metastasis. There are a lot of cytokines inducing EMT of tumor cells, EGF is one of the important cytokines.Ezrin is a connexin between the cytoskeleton and the cell membrane, which is closely related to the morphological movement and metastasis of tumor cells.EGF can activate Ezrin and affects cell motility. In recent years, many studies have shown that NF-kB acts as an important transcription factor, involving in the process of EMT...
May 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28535201/regulatory-t-cells-ameliorate-tissue-plasminogen-activator-induced-brain-haemorrhage-after-stroke
#6
Leilei Mao, Peiying Li, Wen Zhu, Wei Cai, Zongjian Liu, Yanling Wang, Wenli Luo, Ruth A Stetler, Rehana K Leak, Weifeng Yu, Yanqin Gao, Jun Chen, Gang Chen, Xiaoming Hu
Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia...
May 22, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28535182/characterization-of-liver-injury-oval-cell-proliferation-and-cholangiocarcinogenesis-in-glutathione-s-transferase-a3-knockout-mice
#7
Dana R Crawford, Zoran Ilic, Ian Guest, Ginger L Milne, John D Hayes, Stewart Sell
We recently generated glutathione S-transferase (GST) A3 knockout (KO) mice as a novel model to study the risk factors for liver cancer. GSTA3 KO mice are sensitive to the acute cytotoxic and genotoxic effects of aflatoxin B1 (AFB1), confirming the crucial role of GSTA3 in resistance to AFB1. We now report histopathological changes, tumor formation, biochemical changes and gender response following AFB1 treatment as well as the contribution of oxidative stress. Using a protocol of weekly 0.5 mg AFB1/kg administration, we observed extensive oval (liver stem) cell (OC) proliferation within 1-3 weeks followed by microvesicular lipidosis, megahepatocytes, nuclear inclusions, cholangiomas, and small nodules...
May 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28535009/microrna-let-7g-alleviates-atherosclerosis-via-the-targeting-of-lox-1-in-vitro-and-in-vivo
#8
Mingxin Liu, Guizhou Tao, Qifeng Liu, Kun Liu, Xinchun Yang
Atherosclerosis is a chronic arterial disease and the leading cause of stroke and myocardial infarction. Micro-RNAs (miRNAs or miRs) have been reported to act as essential modulators during the progression of atherosclerosis. Although miR-let-7g has been demonstrated to contribute to maintaining endothelial function and vascular homeostasis, it is not known whether miR-let-7g exerts a therapeutic effect on experimental atherosclerosis. The aim of this study was to investigate the effects of miR-let-7g on atherosclerosis in vivo and in vitro and to explore its underlying mechanisms...
May 18, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28534931/leucine-rich-glioma-inactivated-3-integrative-analyses-support-its-role-in-the-cytokine-network
#9
Hyun A Kim, Nyoun Soo Kwon, Kwang Jin Baek, Dong-Seok Kim, Hye-Young Yun
Leucine-rich glioma inactivated (LGI)3 is a secreted protein member of LGI family. We previously repo-rted that LGI3 was upregulated in adipose tissues from obese mice and suppressed adipogenesis through its receptor, a disintegrin and metalloproteinase domain-containing protein 23 (ADAM23). We demonstrated that LGI3 regulated tumor necrosis factor-α and adiponectin, and proposed that LGI3 may be a pro-inflammatory adipokine involved in adipose tissue inflammation. In this study, we analyzed adipokine and cytokine profiles in LGI3 knockout mice and demonstrated that multiple factors were increased or decreased in the adipose tissues and plasma of the LGI3 knockout mice...
May 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28534515/stat3-activation-in-endothelial-cells-is-important-for-tumor-metastasis-via-increased-cell-adhesion-molecule-expression
#10
K-J Kim, S-H Kwon, J-H Yun, H-S Jeong, H-R Kim, E H Lee, S-K Ye, C-H Cho
Metastasis is a life-threatening feature of cancer and is primarily responsible for cancer patient mortality. Cross talk between tumor cells and endothelium is important for tumor progression and metastasis. However, very little is known about the mechanisms by which endothelial cells (ECs) that are close to tumor cells, respond to the tumor cells during tumor progression and metastasis. In this study, we exploited the use of EC-specific signal transducer activator of transcription 3 (STAT3) knockout mice to investigate the role of STAT3 in ECs in tumor progression and metastasis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534495/exercise-induces-cerebral-vegf-and-angiogenesis-via-the-lactate-receptor-hcar1
#11
Cecilie Morland, Krister A Andersson, Øyvind P Haugen, Alena Hadzic, Liv Kleppa, Andreas Gille, Johanne E Rinholm, Vuk Palibrk, Elisabeth H Diget, Lauritz H Kennedy, Tomas Stølen, Eivind Hennestad, Olve Moldestad, Yiqing Cai, Maja Puchades, Stefan Offermanns, Koen Vervaeke, Magnar Bjørås, Ulrik Wisløff, Jon Storm-Mathisen, Linda H Bergersen
Physical exercise can improve brain function and delay neurodegeneration; however, the initial signal from muscle to brain is unknown. Here we show that the lactate receptor (HCAR1) is highly enriched in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in pericyte-like cells along intracerebral microvessels. Activation of HCAR1 enhances cerebral vascular endothelial growth factor A (VEGFA) and cerebral angiogenesis. High-intensity interval exercise (5 days weekly for 7 weeks), as well as L-lactate subcutaneous injection that leads to an increase in blood lactate levels similar to exercise, increases brain VEGFA protein and capillary density in wild-type mice, but not in knockout mice lacking HCAR1...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28534493/usp13-negatively-regulates-antiviral-responses-by-deubiquitinating-sting
#12
He Sun, Qiang Zhang, Ying-Ying Jing, Man Zhang, Hai-Ying Wang, Zeng Cai, Tianzi Liuyu, Zhi-Dong Zhang, Tian-Chen Xiong, Yan Wu, Qi-Yun Zhu, Jing Yao, Hong-Bing Shu, Dandan Lin, Bo Zhong
STING (also known as MITA) is critical for host defence against viruses and the activity of STING is regulated by ubiquitination. However, the deubiquitination of STING is not fully understood. Here, we show that ubiquitin-specific protease 13 (USP13) is a STING-interacting protein that catalyses deubiquitination of STING. Knockdown or knockout of USP13 potentiates activation of IRF3 and NF-κB and expression of downstream genes after HSV-1 infection or transfection of DNA ligands. USP13 deficiency results in impaired replication of HSV-1...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28534119/splenic-ly6c-hi-monocytes-contribute-to-adverse-late-post-ischemic-left-ventricular-remodeling-in-heme-oxygenase-1-deficient-mice
#13
Mateusz Tomczyk, Izabela Kraszewska, Krzysztof Szade, Karolina Bukowska-Strakova, Marco Meloni, Alicja Jozkowicz, Jozef Dulak, Agnieszka Jazwa
Heme oxygenase-1 (Hmox1) is a stress-inducible protein crucial in heme catabolism. The end products of its enzymatic activity possess anti-oxidative, anti-apoptotic and anti-inflammatory properties. Cardioprotective effects of Hmox1 were demonstrated in experimental models of myocardial infarction (MI). Nevertheless, its importance in timely resolution of post-ischemic inflammation remains incompletely understood. The aim of this study was to determine the role of Hmox1 in the monocyte/macrophage-mediated cardiac remodeling in a mouse model of MI...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28533980/mitochondrial-complex-i-deficiency-leads-to-the-retardation-of-early-embryonic-development-in-ndufs4-knockout-mice
#14
Mei Wang, Ya-Ping Huang, Han Wu, Ke Song, Cong Wan, A-Ni Chi, Ya-Mei Xiao, Xiao-Yang Zhao
BACKGROUND: The NDUFS4 gene encodes an 18-kD subunit of mitochondria complex I, and mutations in this gene lead to the development of a severe neurodegenerative disease called Leigh syndrome (LS) in humans. To investigate the disease phenotypes and molecular mechanisms of Leigh syndrome, the Ndufs4 knockout (KO) mouse has been widely used as a novel animal model. Because the homozygotes cannot survive beyond child-bearing age, whether Ndufs4 and mitochondrial complex I influence early embryonic development remains unknown...
2017: PeerJ
https://www.readbyqxmd.com/read/28533928/leucine-nicotinic-acid-synergy-stimulates-ampk-sirt1-signaling-and-regulates-lipid-metabolism-and-lifespan-in-caenorhabditis-elegans-and-hyperlipidemia-and-atherosclerosis-in-mice
#15
Antje Bruckbauer, Jheelam Banerjee, Quiang Cao, Xin Cui, Jia Jing, Lin Zha, Fenfen Li, Bingzhong Xue, Hang Shi, Michael B Zemel
BACKGROUND/AIMS: Nicotinic acid (NA), a lipid-lowering drug, serves as a source of NAD(+), the cofactor for Sirt1. Leucine (Leu) stimulates the AMPK/Sirt1 axis and amplifies the effects of other AMPK/Sirt1 activating compounds. Therefore, we tested the interactive effects of leucine and low dose NA on AMPK/Sirt1 signaling and downstream effects of lipid metabolism in cell culture, C. elegans and mice. METHODS: LDL-receptor knockout mice were fed an atherogenic Western diet supplemented with leucine (24 g/kg diet) and sub-therapeutic NA combinations (50 mg/kg diet and 250 mg/kg diet) or low therapeutic NA (1000 mg/kg diet) for 8 weeks to evaluate markers of hyperlipidemia and atherosclerosis...
2017: American Journal of Cardiovascular Disease
https://www.readbyqxmd.com/read/28533515/perivascular-aqp4-dysregulation-in-the-hippocampal-ca1-area-after-traumatic-brain-injury-is-alleviated-by-adenosine-a2a-receptor-inactivation
#16
Zi-Ai Zhao, Ping Li, Shi-Yang Ye, Ya-Lei Ning, Hao Wang, Yan Peng, Nan Yang, Yan Zhao, Zhuo-Hang Zhang, Jiang-Fan Chen, Yuan-Guo Zhou
Traumatic brain injury (TBI) can induce cognitive dysfunction due to the regional accumulation of hyperphosphorylated tau protein (p-tau). However, the factors that cause p-tau to concentrate in specific brain regions remain unclear. Here, we show that AQP4 polarization in the perivascular astrocytic end feet was impaired after TBI, which was most prominent in the ipsilateral brain tissue surrounding the directly impacted region and the contralateral hippocampal CA1 area and was accompanied by increased local p-tau, changes in dendritic spine density and morphology, and upregulation of the adenosine A2A receptor (A2AR)...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533359/selective-regulation-of-notch-ligands-during-angiogenesis-is-mediated-by-vimentin
#17
Daniel Antfolk, Marika Sjöqvist, Fang Cheng, Kimmo Isoniemi, Camille L Duran, Adolfo Rivero-Muller, Christian Antila, Rasmus Niemi, Sebastian Landor, Carlijn V C Bouten, Kayla J Bayless, John E Eriksson, Cecilia M Sahlgren
Notch signaling is a key regulator of angiogenesis, in which sprouting is regulated by an equilibrium between inhibitory Dll4-Notch signaling and promoting Jagged-Notch signaling. Whereas Fringe proteins modify Notch receptors and strengthen their activation by Dll4 ligands, other mechanisms balancing Jagged and Dll4 signaling are yet to be described. The intermediate filament protein vimentin, which has been previously shown to affect vascular integrity and regenerative signaling, is here shown to regulate ligand-specific Notch signaling...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533336/a-coding-variant-in-the-gene-bardet-biedl-syndrome-4-bbs4-is-associated-with-a-novel-form-of-canine-progressive-retinal-atrophy
#18
Tracy Chew, Bianca Haase, Roslyn Bathgate, Cali E Willet, Maria K Kaukonen, Lisa J Mascord, Hannes T Lohi, Claire M Wade
Progressive retinal atrophy is a common cause of blindness in the dog and affects over 100 breeds. It is characterized by gradual vision loss that occurs due to the degeneration of photoreceptor cells in the retina. Similar to the human counterpart retinitis pigmentosa, the canine disorder is clinically and genetically heterogeneous and the underlying cause remains unknown for many cases. We use a positional candidate gene approach to identify putative variants in the Hungarian Puli breed using genotyping data of 14 family-based samples (CanineHD BeadChip array, Illumina) and whole genome sequencing data of two proband and two parental samples (Illumina HiSeq 2000)...
May 22, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28533326/prostaglandin-e-receptor-subtype-4-regulates-lipid-droplet-size-and-mitochondrial-activity-in-murine-subcutaneous-white-adipose-tissue
#19
Fan Ying, Yin Cai, Yu Cai, Yu Wang, Eva Hoi Ching Tang
The purpose of this study was to investigate whether genetic ablation of prostaglandin E receptor subtype 4 (EP4) affects white adipose tissue (WAT) remodeling mediated by β3-adrenergic stimulation. The selective β3-adrenergic agonist, CL316243 (1 mg/kg/d, i.p.) caused a greater increase in metabolic rate in EP4-knockout mice. CL316243 fragmented the unilocular lipid droplet into multilocular lipid vacuoles and increased mitochondrial biogenesis and its activity. These changes were amplified in mice with EP4 deficiency and were selectively seen in subcutaneous WAT...
May 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28533325/physiologic-regulation-of-heart-rate-and-blood-pressure-involves-connexin-36-containing-gap-junctions
#20
Varinder K Lall, Gareth Bruce, Larysa Voytenko, Mark Drinkhill, Kerstin Wellershaus, Klaus Willecke, Jim Deuchars, Susan A Deuchars
Chronically elevated sympathetic nervous activity underlies many cardiovascular diseases. Elucidating the mechanisms contributing to sympathetic nervous system output may reveal new avenues of treatment. The contribution of the gap junctional protein connexin 36 (Cx36) to the regulation of sympathetic activity and thus blood pressure and heart rate was determined using a mouse with specific genetic deletion of Cx36. Ablation of the Cx36 protein was confirmed in sympathetic preganglionic neurons of Cx36 knockout (KO) mice...
May 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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