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https://www.readbyqxmd.com/read/27908781/heme-oxygenase-1-metabolite-biliverdin-not-iron-inhibits-porcine-reproductive-and-respiratory-syndrome-virus-replication
#1
Angke Zhang, Hong Duan, Na Li, Lijuan Zhao, Fengxing Pu, Baicheng Huang, Chunyan Wu, Yuchen Nan, Taofeng Du, Yang Mu, Qin Zhao, Yani Sun, Gaiping Zhang, Julian A Hiscox, En-Min Zhou, Shuqi Xiao
Porcinereproductiveandrespiratorysyndromevirus (PRRSV) causes significant economic losses to the pork industry worldwide. Previously, we demonstrated that heme oxygenase-1 (HO-1) interferes with PRRSV replication. To elucidate the mechanisms involved, here we assess whether the HO-1 downstream metabolites biliverdin (BV) and/or iron mediate the HO-1 antiviral effect. We demonstrate a BV concentration-dependent suppression of PRRSV replication and show that virions are not directly inactivated by BV. Additionally, BV or N-acetyl cysteine (NAC) significantly reduced reactive oxygen species (ROS) in PRRSV-infected MARC-145 cells; however, because NAC did not reduce viral load, the BV antiviral effect is independent of decreased ROS levels...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27904664/tauroursodeoxycholic-acid-inhibits-endoplasmic-reticulum-stress-blocks-mitochondrial-permeability-transition-pore-opening-and-suppresses-reperfusion-injury-through-gsk-3%C3%A3-in-cardiac-h9c2-cells
#2
Yuxi Xie, Yonggui He, Zhiliang Cai, Jianhang Cai, Mengyao Xi, Yidong Zhang, Jinkun Xi
This study investigates whether inhibition of endoplasmic reticulum (ER) stress prevents opening of the mitochondrial permeability transition pore (mPTP) and evaluates the corresponding signaling pathways involved in this process. Exposure of cardiac H9c2 cells to 800 µM H2O2 for 20 min opened mPTP in response to oxidative stress, as demonstrated by quenching of tetramethylrhodamine ethyl ester (TMRE) fluorescence. Oxidative stress-induced mPTP opening was rescued by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) in a dose-dependent manner at low concentrations...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27899719/a-novel-hypothesis-for-histone-to-protamine-transition-in-bos-taurus-spermatozoa
#3
Gerly Sillaste, Lauris Kaplinski, Riho Meier, Ülle Jaakma, Elo Eriste, Andres Salumets
DNA compaction with protamines in sperm is essential for successful fertilization. However, a portion of sperm chromatin remains less tightly packed with histones, which genomic location and function remain unclear. We extracted and sequenced histone-associated DNA from sperm of nine ejaculates from three bulls. We found that the fraction of retained histones varied between samples but the variance was similar between samples from the same and different individuals. The most conserved regions showed similar abundance across all samples, while in other regions their presence correlated with the size of histone fraction...
November 29, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27895156/sildenafil-prevents-podocyte-injury-via-ppar-%C3%AE-mediated-trpc6-inhibition
#4
Ramon Sonneveld, Joost G Hoenderop, Andrea M Isidori, Carole Henique, Henry B Dijkman, Jo H Berden, Pierre-Louis Tharaux, Johan van der Vlag, Tom Nijenhuis
Transient receptor potential channel C6 (TRPC6) gain-of-function mutations and increased TRPC6 expression in podocytes induce glomerular injury and proteinuria. Sildenafil reduces TRPC6 expression and activity in nonrenal cell types, although the mechanism is unknown. Peroxisome proliferator-activated receptor γ (PPAR-γ) is a downstream target of sildenafil in the cyclic guanosine monophosphate (cGMP)-activated protein kinase G (PKG) axis. PPAR-γ agonists, like pioglitazone, appear antiproteinuric. We hypothesized that sildenafil inhibits TRPC6 expression in podocytes through PPAR-γ-dependent mechanisms, thereby counteracting podocyte injury and proteinuria...
November 28, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27890915/pharmacological-evidence-a-new-therapeutic-approach-to-the-treatment-of-chronic-heart-failure-through-sur2b-kir6-1-channel-in-endothelial-cells
#5
Shang Wang, Chao-Liang Long, Jun Chen, Wen-Yu Cui, Yan-Fang Zhang, Hao Zhang, Hai Wang
Both iptakalim (Ipt) and natakalim (Nat) activate the SUR2B/Kir6.1 channel, an ATP-sensitive potassium channel (KATP) subtype, with high selectivity. In this study we investigated the therapeutic effects of Ipt and Nat against isoproterenol-induced chronic heart failure (ISO-CHF) in rats, and demonstrated a new therapeutic approach to the treatment of CHF through activation of the SUR2B/Kir6.1 channel in endothelial cells. In ISO-CHF rats, oral administration of Nat (1, 3, 9 mg·kg(-1)·d(-1)) or Ipt (3 mg·kg(-1)·d(-1)) for 60 days significantly improved cardiac dysfunction, reversed cardiac remodeling, significantly attenuated the pathological increases in BNP levels, and improved endothelial dysfunction by adjusting the balance between endothelin and NO systems...
November 28, 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27885524/camp-dependent-protein-kinase-and-cgmp-dependent-protein-kinase-as-cyclic-nucleotide-effectors
#6
Robin Lorenz, Daniela Bertinetti, Friedrich W Herberg
The cAMP-dependent protein kinase (PKA) and the cGMP-dependent protein kinase (PKG) are homologous enzymes with different binding and activation specificities for cyclic nucleotides. Both enzymes harbor conserved cyclic nucleotide-binding (CNB) domains. Differences in amino acid composition of these CNB domains mediate cyclic nucleotide selectivity in PKA and PKG, respectively. Recently, the presence of the noncanonical cyclic nucleotides cCMP and cUMP in eukaryotic cells has been proven, while the existence of cellular cIMP and cXMP remains unclear...
November 25, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27861632/cgmp-phosphodiesterase-inhibition-prevents-hypoxia-induced-cell-death-activation-in-porcine-retinal-explants
#7
Lorena Olivares-González, Cristina Martínez-Fernández de la Cámara, David Hervás, María Pilar Marín, Agustin Lahoz, José María Millán, Regina Rodrigo
Retinal hypoxia and oxidative stress are involved in several retinal degenerations including diabetic retinopathy, glaucoma, central retinal artery occlusion, or retinopathy of prematurity. The second messenger cyclic guanosine monophosphate (cGMP) has been reported to be protective for neuronal cells under several pathological conditions including ischemia/hypoxia. The purpose of this study was to evaluate whether the accumulation of cGMP through the pharmacological inhibition of phosphodiesterase (PDE) with Zaprinast prevented retinal degeneration induced by mild hypoxia in cultures of porcine retina...
2016: PloS One
https://www.readbyqxmd.com/read/27842852/characteristics-of-glucomannan-isolated-from-fresh-tuber-of-porang-amorphophallus-muelleri-blume
#8
Anny Yanuriati, Djagal Wiseso Marseno, Rochmadi, Eni Harmayani
Porang is a potential source of glucomannan. This research objective was to find a direct glucomannan isolation method from fresh porang corm to produce high purity glucomannan. Two isolation methods were performed. In first method, sample was water dissolved using Al2(SO4)3 as flocculant for 15 (AA15) or 30 (AA30) minutes with purification. In second method, sample was repeatedly milled using ethanol as solvent and filtered for 5 (EtOH5) or 7 (EtOH7) times without purification. The characteristics of obtained glucomannan were compared to those of commercial porang flour (CPF) and purified konjac glucomannan (PKG)...
January 20, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/27836585/neuroprotective-effects-of-sildenafil-against-oxidative-stress-and-memory-dysfunction-in-mice-exposed-to-noise-stress
#9
Hu Erxidan Sikandaner, So Young Park, Min Jung Kim, Shi Nae Park, Dong Won Yang
Noise exposure has been well characterized as an environmental stressor, and is known to have auditory and non-auditory effects. Phosphodiesterase 5 (PDE5) inhibitors affect memory and hippocampus plasticity through various signaling cascades which are regulated by cGMP. In this study, we investigated the effects of sildenafil on memory deficiency, neuroprotection and oxidative stress in mice caused by chronic noise exposure. Mice were exposed to noise for 4h every day up to 14days at 110dB SPL of noise level...
November 9, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27833146/activation-of-protein-kinase-g-pkg-reduces-neointimal-hyperplasia-inhibits-platelet-aggregation-and-facilitates-re-endothelialization
#10
Ju-Young Kim, Han-Mo Yang, Joo-Eun Lee, Baek-Kyung Kim, Sooryeonhwa Jin, Jaewon Lee, Kyung-Woo Park, Hyun-Jai Cho, Yoo-Wook Kwon, Hae-Young Lee, Hyun-Jae Kang, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
In spite of its great success in reducing restenosis, drug-eluting stent (DES) has unfavorable aspects such as stent thrombosis and delayed re-endothelialization. We examined the effects of PKG activation by Exisulind on neointimal formation, platelet aggregation, and re-endothelialization. Exisulind significantly reduced VSMCs viability, cell cycle progression, migration, and neointimal hyperplasia after vascular injury in rat carotid arteries. Interestingly, in contrast to the effect on VSMC viability, Exisulind did not reduce the viability of endothelial cells...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27822383/neuronal-nitric-oxide-synthase-in-hypertension-an-update
#11
REVIEW
Yin Hua Zhang
Hypertension is a prevalent condition worldwide and is the key risk factor for fatal cardiovascular complications, such as stroke, sudden cardiac death and heart failure. Reduced bioavailability of nitric oxide (NO) in the endothelium is an important precursor for impaired vasodilation and hypertension. In the heart, NO deficiency deteriorates the adverse consequences of pressure-overload and causes cardiac hypertrophy, fibrosis and myocardial infarction which lead to fatal heart failure and sudden cardiac death...
2016: Clinical Hypertension
https://www.readbyqxmd.com/read/27799868/antibody-based-proteomics-to-identify-an-apoptosis-signature-for-early-recurrence-of-hepatocellular-carcinoma
#12
Noriaki Morofuji, Hidenori Ojima, Nobuyoshi Hiraoka, Takuji Okusaka, Minoru Esaki, Satoshi Nara, Kazuaki Shimada, Yoshiro Kishi, Tadashi Kondo
BACKGROUND: Early recurrence after surgical resection is a hallmark of poor prognosis in hepatocellular carcinoma (HCC). To determine the proteomic background of early recurrence of HCC, we focused on apoptosis-related proteins. METHODS: Surgically resected tumor tissues were obtained from 80 patients, including HCC tumor tissues, non-tumor tissues, and normal liver tissues. These samples were grouped in the discovery and validation sample sets. The expression level of 192 apoptosis-related proteins was monitored using 247 commercially available antibodies and western blotting...
2016: Clinical Proteomics
https://www.readbyqxmd.com/read/27798640/altered-expression-of-human-smooth-muscle-myosin-phosphatase-targeting-mypt-isovariants-with-pregnancy-and-labor
#13
Jon Lartey, Julie Taggart, Stephen Robson, Michael Taggart
BACKGROUND: Myosin light-chain phosphatase is a trimeric protein that hydrolyses phosphorylated myosin II light chains (MYLII) to cause relaxation in smooth muscle cells including those of the uterus. A major component of the phosphatase is the myosin targeting subunit (MYPT), which directs a catalytic subunit to dephosphorylate MYLII. There are 5 main MYPT family members (MYPT1 (PPP1R12A), MYPT2 (PPP1R12B), MYPT3 (PPP1R16A), myosin binding subunit 85 MBS85 (PPP1R12C) and TIMAP (TGF-beta-inhibited membrane-associated protein (PPP1R16B))...
2016: PloS One
https://www.readbyqxmd.com/read/27795439/carbon-monoxide-inhibits-porcine-reproductive-and-respiratory-syndrome-virus-replication-by-the-cgmp-pkg-and-nf-%C3%AE%C2%BAb-signaling-pathway
#14
Angke Zhang, Lijuan Zhao, Na Li, Hong Duan, Hongliang Liu, Fengxing Pu, Gaiping Zhang, En-Min Zhou, Shuqi Xiao
: Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses to the pork industry worldwide each year. Our previous research had demonstrated that heme oxygenase-1 (HO-1) can suppress PRRSV replication via an unknown molecular mechanism. In this study, inhibition of PRRSV replication was demonstrated to be mediated by carbon monoxide (CO), a downstream metabolite of HO-1. Using several approaches, we demonstrate that CO significantly inhibited PRRSV replication in both PRRSV permissive cell line, MARC-145, and the predominant cell type targeted during in vivo PRRSV infection, porcine alveolar macrophages (PAMs)...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27784679/hydrogen-sulfide-an-enhancer-of-vascular-nitric-oxide-signalling-mechanisms-and-implications
#15
Csaba Szabo
Nitric oxide (NO) vascular signalling has long been considered an independent, self-sufficient pathway. However, recent data indicate that the novel gaseous mediator, hydrogen sulfide (H2S), serves as an essential enhancer/stimulator of vascular NO signalling. The current article overviews the multiple levels at which this enhancement/stimulation takes place. The first level of interaction relates to the formation of biologically active hybrid S/N species and the stimulation of NO release from its various stable "pools" (e...
October 26, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27774770/protection-of-nrf2-against-arsenite-induced-oxidative-damage-is-regulated-by-the-cyclic-guanosine-monophosphate-protein-kinase-g-signaling-pathway
#16
Chengzhi Chen, Xuejun Jiang, Shiyan Gu, Yanhao Lai, Yuan Liu, Zunzhen Zhang
Arsenite has been shown to induce a variety of oxidative damage in mammalian cells. However, the mechanisms underlying cellular responses to its adverse effects remain unknown. We previously showed that the level of Nrf2, a nuclear transcription factor significantly increased in arsenite-treated human bronchial epithelial (HBE) cells suggesting that Nrf2 is involved in responding to arsenite-induced oxidative damage. To explore how Nrf2 can impact arsenite-induced oxidative damage, in this study, we examined Nrf2 activation and its regulation upon cellular arsenite exposure as well as its effects on arsenite-induced oxidative damage in HBE cells...
October 24, 2016: Environmental Toxicology
https://www.readbyqxmd.com/read/27768311/ip3-mediates-nitric-oxide-guanosine-3-5-cyclic-monophosphate-no-cgmp-induced-isoflavone-accumulation-in-soybean-sprouts-under-uv-b-radiation
#17
Caifeng Jiao, Pei Wang, Runqiang Yang, Lu Tian, Zhenxin Gu
In this study, to investigate the role of inositol 1,4,5-trisphosphate (IP3) in nitric oxide-guanosine 3',5'-cyclic monophosphate (NO-cGMP)-induced isoflavone accumulation in soybean sprouts under UV-B radiation, the sprouts were treated with donors and inhibitors of NO and cGMP as well as IP3 inhibitor. Results showed that NO, with cGMP as a second messenger, stimulates IP3 accumulation under UV-B radiation. Consistent with the increase in IP3 content, the up-regulation of gene and protein expression of phosphoinositide-specific phospholipase C (PI-PLC) in response to sodium nitroprusside (SNP) (exogenous NO donor) and 8-Br-cGMP (cGMP analogue) was also observed...
October 28, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27747306/chemotherapeutic-efficacy-of-phosphodiesterase-inhibitors-in-chagasic-cardiomyopathy
#18
Jian-Jun Wen, Xianxiu Wan, John Thacker, Nisha Jain Garg
BACKGROUND: Chagasic cardiomyopathy (CCM) caused by Trypanosoma cruzi (Tc) infection is prevalent in Latin America and recognized as an emerging infectious heart disease in the US. The NO-cGMP-PKG1α pathway maintains cardiac homeostasis and inotropy and may be disturbed due to phosphodiesterase (PDE5) mediated cGMP catabolism in CCM. METHODS AND RESULTS: C57BL/6 mice were infected with Tc, and at the end of acute parasitemia (i.e. 45 days post-infection), treated with sildenafil (SIL, 1 mg/kg) twice per week for 3 weeks...
June 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/27730393/privacy-preserving-and-secure-sharing-of-phr-in-the-cloud
#19
Leyou Zhang, Qing Wu, Yi Mu, Jingxia Zhang
As a new summarized record of an individual's medical data and information, Personal Health Record (PHR) can be accessible online. The owner can control fully his/her PHR files to be shared with different users such as doctors, clinic agents, and friends. However, in an open network environment like in the Cloud, these sensitive privacy information may be gotten by those unauthorized parties and users. In this paper, we consider how to achieve PHR data confidentiality and provide fine-grained access control of PHR files in the public Cloud based on Attribute Based Encryption(ABE)...
December 2016: Journal of Medical Systems
https://www.readbyqxmd.com/read/27729550/pressure-induced-oxidative-activation-of-pkg-enables-vasoregulation-by-ca2-sparks-and-bk-channels
#20
Kaivan Khavandi, Rachael L Baylie, Sarah A Sugden, Majid Ahmed, Viktoria Csato, Philip Eaton, David C Hill-Eubanks, Adrian D Bonev, Mark T Nelson, Adam S Greenstein
Activation of Ca(2+)-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca(2+) signals (Ca(2+) sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries. We report that physiological intraluminal pressure within resistance arteries activated cGMP-dependent protein kinase (PKG) in VSMCs through oxidant-induced formation of an intermolecular disulfide bond between cysteine residues...
October 11, 2016: Science Signaling
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