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  1. Article ; Online: Interleukin-10 -1082 G/A polymorphism and its association with early or severe presentation of coronary artery disease: A systematic review and meta-analysis.

    Rai, Himanshu / Joner, Michael / Wilson, Hannah / McGovern, Laurna / Richards, Gavin / Colleran, Roisin / Byrne, Robert A

    Cytokine

    2022  Volume 162, Page(s) 156103

    Abstract: ... rupture. A guanine (G) to adenine (A) substitution in the IL-10 gene at -1082 bp (rs1800896) has been ...

    Abstract Introduction: Interleukin-10 (IL-10) is an anti-inflammatory cytokine with potent deactivating properties on macrophages and T cells; and plays an important role in atherosclerotic plaque maturation and rupture. A guanine (G) to adenine (A) substitution in the IL-10 gene at -1082 bp (rs1800896) has been associated with reduced in IL-10 production in vitro. Against this background, we tested the association of IL-10 -1082G/A with early or severe presentation of coronary artery disease (CAD) using a systematic review and updated meta-analysis of published association studies.
    Materials and methods: Relevant studies were identified following a comprehensive online search on PubMed, EMBASE, MEDLINE, Scopus, Cochrane library and Web of Science databases and stratified into two subgroups based on mode of CAD presentation: early or severe and non-severe. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random effects employing a Z test.
    Results: A total of 24 studies were included for quantitative synthesis with a cumulative sample of 19,135 (11,143 cases / 7,992 controls). A significant association was derived for IL-10 -1082G/A and early or severe CAD via dominant, recessive, and allelic genetic model comparisons [OR 1.24 (95 % CI 1.02, 1.50), p = 0.03; OR 1.32 (95 % CI 1.03, 1.69), p = 0.03 and OR 1.18 (95 % CI 1.02, 1.36), p = 0.02 respectively]. In contrast, no significant association was seen for the pooled group or non-severe CAD subgroup (p = NS). Sensitivity analysis showed consistent results.
    Conclusions: IL-10 -1082G/A appears to be associated with early or severe presentation of CAD. Further studies are warranted to confirm this association.
    MeSH term(s) Humans ; Coronary Artery Disease/genetics ; Interleukin-10/genetics ; Polymorphism, Single Nucleotide/genetics ; Genetic Predisposition to Disease ; Gene Expression
    Chemical Substances Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2022-12-01
    Publishing country England
    Document type Meta-Analysis ; Systematic Review ; Journal Article ; Review
    ZDB-ID 1018055-2
    ISSN 1096-0023 ; 1043-4666
    ISSN (online) 1096-0023
    ISSN 1043-4666
    DOI 10.1016/j.cyto.2022.156103
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    Zs.A 2840: Show issues Location:
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  2. Article ; Online: Loss of Hepatic Leucine-Rich Repeat-Containing G-Protein Coupled Receptors 4 and 5 Promotes Nonalcoholic Fatty Liver Disease.

    Saponara, Enrica / Penno, Carlos / Orsini, Vanessa / Wang, Zhong-Yi / Fischer, Audrey / Aebi, Alexandra / Matadamas-Guzman, Meztli L / Brun, Virginie / Fischer, Benoit / Brousseau, Margaret / O'Donnell, Peter / Turner, Jonathan / Graff Meyer, Alexandra / Bollepalli, Laura / d'Ario, Giovanni / Roma, Guglielmo / Carbone, Walter / Annunziato, Stefano / Obrecht, Michael /
    Beckmann, Nicolau / Saravanan, Chandra / Osmont, Arnaud / Tropberger, Philipp / Richards, Shola M / Genoud, Christel / Ley, Svenja / Ksiazek, Iwona / Nigsch, Florian / Terracciano, Luigi M / Schadt, Heiko S / Bouwmeester, Tewis / Tchorz, Jan S / Ruffner, Heinz

    The American journal of pathology

    2022  Volume 193, Issue 2, Page(s) 161–181

    Abstract: The roof plate-specific spondin-leucine-rich repeat-containing G-protein coupled receptor 4/5 (LGR4 ...

    Abstract The roof plate-specific spondin-leucine-rich repeat-containing G-protein coupled receptor 4/5 (LGR4/5)-zinc and ring finger 3 (ZNRF3)/ring finger protein 43 (RNF43) module is a master regulator of hepatic Wnt/β-catenin signaling and metabolic zonation. However, its impact on nonalcoholic fatty liver disease (NAFLD) remains unclear. The current study investigated whether hepatic epithelial cell-specific loss of the Wnt/β-catenin modulator Lgr4/5 promoted NAFLD. The 3- and 6-month-old mice with hepatic epithelial cell-specific deletion of both receptors Lgr4/5 (Lgr4/5dLKO) were compared with control mice fed with normal diet (ND) or high-fat diet (HFD). Six-month-old HFD-fed Lgr4/5dLKO mice developed hepatic steatosis and fibrosis but the control mice did not. Serum cholesterol-high-density lipoprotein and total cholesterol levels in 3- and 6-month-old HFD-fed Lgr4/5dLKO mice were decreased compared with those in control mice. An ex vivo primary hepatocyte culture assay and a comprehensive bile acid (BA) characterization in liver, plasma, bile, and feces demonstrated that ND-fed Lgr4/5dLKO mice had impaired BA secretion, predisposing them to develop cholestatic characteristics. Lipidome and RNA-sequencing analyses demonstrated severe alterations in several lipid species and pathways controlling lipid metabolism in the livers of Lgr4/5dLKO mice. In conclusion, loss of hepatic Wnt/β-catenin activity by Lgr4/5 deletion led to loss of BA secretion, cholestatic features, altered lipid homeostasis, and deregulation of lipoprotein pathways. Both BA and intrinsic lipid alterations contributed to the onset of NAFLD.
    MeSH term(s) Animals ; Mice ; Non-alcoholic Fatty Liver Disease/metabolism ; beta Catenin/metabolism ; Leucine/metabolism ; Liver/metabolism ; Cholesterol/metabolism ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects
    Chemical Substances beta Catenin ; Leucine (GMW67QNF9C) ; Cholesterol (97C5T2UQ7J) ; Receptors, G-Protein-Coupled
    Language English
    Publishing date 2022-11-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.1016/j.ajpath.2022.10.008
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  3. Article ; Online: Merton G. Henry

    David Richards

    Maine Policy Review, Vol 27, Iss

    A Legacy of Leadership

    2018  Volume 1

    Keywords leadership ; maine ; margaret chase smith ; Social Sciences ; H ; Political institutions and public administration (General) ; JF20-2112
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Margaret Chase Smith Policy Center
    Document type Article ; Online
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  4. Article ; Online: Profusion of G-quadruplexes on both subunits of metazoan ribosomes.

    Mestre-Fos, Santi / Penev, Petar I / Richards, John Colin / Dean, William L / Gray, Robert D / Chaires, Jonathan B / Williams, Loren Dean

    PloS one

    2019  Volume 14, Issue 12, Page(s) e0226177

    Abstract: ... that favor G-quadruplexes in silico and in vitro in rRNA tentacles of the human large ribosomal subunit ... We demonstrated by experiment that these sequences form G-quadruplexes in vitro. Here, using a more recent motif ... definition, we report additional G-quadruplex sequences on surfaces of both subunits of the human ribosome ...

    Abstract Mammalian and bird ribosomes are nearly twice the mass of prokaryotic ribosomes in part because of their extraordinarily long rRNA tentacles. Human rRNA tentacles are not fully observable in current three-dimensional structures and their conformations remain to be fully resolved. In previous work we identified sequences that favor G-quadruplexes in silico and in vitro in rRNA tentacles of the human large ribosomal subunit. We demonstrated by experiment that these sequences form G-quadruplexes in vitro. Here, using a more recent motif definition, we report additional G-quadruplex sequences on surfaces of both subunits of the human ribosome. The revised sequence definition reveals expansive arrays of potential G-quadruplex sequences on LSU tentacles. In addition, we demonstrate by a variety of experimental methods that fragments of the small subunit rRNA form G-quadruplexes in vitro. Prior to this report rRNA sequences that form G-quadruplexes were confined to the large ribosomal subunit. Our combined results indicate that the surface of the assembled human ribosome contains numerous sequences capable of forming G-quadruplexes on both ribosomal subunits. The data suggest conversion between duplexes and G-quadruplexes in response to association with proteins, ions, or other RNAs. In some systems it seems likely that the integrated population of RNA G-quadruplexes may be dominated by rRNA, which is the most abundant cellular RNA.
    MeSH term(s) Animals ; Base Sequence ; G-Quadruplexes ; Humans ; Nucleic Acid Conformation ; Phylogeny ; RNA, Messenger/chemistry ; RNA, Ribosomal/chemistry ; Ribosome Subunits/chemistry ; Ribosomes/chemistry ; Sequence Homology
    Chemical Substances RNA, Messenger ; RNA, Ribosomal
    Language English
    Publishing date 2019-12-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0226177
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  5. Article ; Online: Meta-QTL for morphological traits and pharmaceutical alkaloids in periwinkle (Catharanthus roseus (L.) ‘G. Don’)

    Shariatipour, Nikwan / Heidari, Bahram / Richards, Christopher

    The Journal of Horticultural Science and Biotechnology. 2023 Jan. 02, v. 98, no. 1 p.87-98

    2023  

    Abstract: Meta-analysis is a powerful method used to discern reliable genomic regions associated with quantitative traits. The objective of this study was to use a meta-QTL (MQTL) analysis method to identify the most reliable and accurate QTL controlling ... ...

    Abstract Meta-analysis is a powerful method used to discern reliable genomic regions associated with quantitative traits. The objective of this study was to use a meta-QTL (MQTL) analysis method to identify the most reliable and accurate QTL controlling morphological traits and terpenoid indole alkaloids (TIAs); serpentine (S), vinblastine (VB), ajmalicine (A) and vincristine (VC) in Catharanthus roseus. A quantitative trait loci (QTL) database containing 40 QTLs retrieved from two individual mapping studies associated with 13 phytochemical and morphological traits. The results of projection of 40 putative QTLs on to the consensus genetic map showed that 18 MQTLs had a 25.88% reduction in confidence interval (CI) on C. roseus chromosomes. Co-localisation results suggested that leaves TAL and serpentine in roots (SR) with 50% and 60% frequencies were the most common QTLs associated with vindoline (V) and catharanthine (C). The MQTL.LG1.5, MQTL.LG2.2, MQTL.LG1.1, MQTL.LG1.2, MQTL.LG1.7 and MQTL.LG3.3 were the most important MQTLs and the most reliable chromosome regions for refining genetic control of the tested traits in C. roseus. The consensus map provided information for the identification of the QTL-dense genomic regions that will assist in improving the efficiency of genomic and marker-assisted selection (MAS) in pharmacological researches.
    Keywords Catharanthus roseus ; biotechnology ; chromosome mapping ; chromosomes ; confidence interval ; databases ; genomics ; horticulture ; marker-assisted selection ; meta-analysis ; phytochemicals ; quantitative traits ; serpentine ; terpenoids ; vinblastine ; vincristine ; Quantitative trait loci ; meta-QTL ; medicinal plants ; alkaloid ; consensus map
    Language English
    Dates of publication 2023-0102
    Size p. 87-98.
    Publishing place Taylor & Francis
    Document type Article ; Online
    ZDB-ID 1416403-6
    ISSN 2380-4084 ; 1462-0316
    ISSN (online) 2380-4084
    ISSN 1462-0316
    DOI 10.1080/14620316.2022.2091485
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    Z 2867: Show issues

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  6. Article ; Online: Impact of a G-CSF Policy to Reduce Low-Value Care on Guideline Adherence and Mortality.

    Orji, Chinelo C / Brown, Carolyn M / Hoverman, J Russell / Richards, Kristin M / Garey, Jody / He, Bo

    JCO oncology practice

    2021  Volume 17, Issue 11, Page(s) e1830–e1836

    Abstract: ... of granulocyte colony-stimulating factors (G-CSFs) in patients with high risk of febrile neutropenia, but evidence suggests that G-CSFs are ... patterns of G-CSF and (2) to evaluate the impact of a program initiative on G-CSF prescribing patterns ... with an aim of reducing G-CSF overutilization. Descriptive statistics, : Results: There were 3,426 ...

    Abstract Purpose: Practice guidelines recommend the prophylactic use of granulocyte colony-stimulating factors (G-CSFs) in patients with high risk of febrile neutropenia, but evidence suggests that G-CSFs are frequently overused. The objectives of this study were (1) to determine the prevalence and prescribing patterns of G-CSF and (2) to evaluate the impact of a program initiative on G-CSF prescribing patterns, adherence to guidelines, and mortality.
    Methods: In this retrospective cohort study, data were used from the electronic health records of patients with metastatic colorectal cancer who received care at a multicenter oncology practice network during two time periods: July 01, 2013, to December 31, 2014, and July 01, 2017, to December 31, 2017. Beginning 2016, a site-wide program initiative that involved educational materials, appropriate nonuse recommendations, and prior authorization was introduced in the oncology practice network with an aim of reducing G-CSF overutilization. Descriptive statistics,
    Results: There were 3,426 chemotherapy regimens corresponding to 2,968 patients. There were a total of 387 (11.3%) G-CSF-treated patients and 3,095 G-CSF administrations during the study period. G-CSF use was significantly lower in the postperiod, compared with the preperiod (
    Conclusion: This study demonstrates that policy initiatives have the potential to positively affect G-CSF prescription patterns and promote guideline adherence. These findings could help prescribers adopt a cost-effective approach in patients with metastatic colorectal cancer, leading to enhanced clinical practice and value-based care.
    MeSH term(s) Granulocyte Colony-Stimulating Factor/therapeutic use ; Guideline Adherence ; Humans ; Low-Value Care ; Neoplasms ; Policy ; Retrospective Studies
    Chemical Substances Granulocyte Colony-Stimulating Factor (143011-72-7)
    Language English
    Publishing date 2021-04-14
    Publishing country United States
    Document type Journal Article ; Multicenter Study
    ZDB-ID 3028198-2
    ISSN 2688-1535 ; 2688-1527
    ISSN (online) 2688-1535
    ISSN 2688-1527
    DOI 10.1200/OP.20.01045
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  7. Article ; Online: Profusion of G-quadruplexes on both subunits of metazoan ribosomes.

    Santi Mestre-Fos / Petar I Penev / John Colin Richards / William L Dean / Robert D Gray / Jonathan B Chaires / Loren Dean Williams

    PLoS ONE, Vol 14, Iss 12, p e

    2019  Volume 0226177

    Abstract: ... that favor G-quadruplexes in silico and in vitro in rRNA tentacles of the human large ribosomal subunit ... We demonstrated by experiment that these sequences form G-quadruplexes in vitro. Here, using a more recent motif ... definition, we report additional G-quadruplex sequences on surfaces of both subunits of the human ribosome ...

    Abstract Mammalian and bird ribosomes are nearly twice the mass of prokaryotic ribosomes in part because of their extraordinarily long rRNA tentacles. Human rRNA tentacles are not fully observable in current three-dimensional structures and their conformations remain to be fully resolved. In previous work we identified sequences that favor G-quadruplexes in silico and in vitro in rRNA tentacles of the human large ribosomal subunit. We demonstrated by experiment that these sequences form G-quadruplexes in vitro. Here, using a more recent motif definition, we report additional G-quadruplex sequences on surfaces of both subunits of the human ribosome. The revised sequence definition reveals expansive arrays of potential G-quadruplex sequences on LSU tentacles. In addition, we demonstrate by a variety of experimental methods that fragments of the small subunit rRNA form G-quadruplexes in vitro. Prior to this report rRNA sequences that form G-quadruplexes were confined to the large ribosomal subunit. Our combined results indicate that the surface of the assembled human ribosome contains numerous sequences capable of forming G-quadruplexes on both ribosomal subunits. The data suggest conversion between duplexes and G-quadruplexes in response to association with proteins, ions, or other RNAs. In some systems it seems likely that the integrated population of RNA G-quadruplexes may be dominated by rRNA, which is the most abundant cellular RNA.
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
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  8. Article ; Online: Randomized study of G-TL and global media for blastocyst culture in the EmbryoScope: morphokinetics, pregnancy, and live births after single-embryo transfer.

    Desai, Nina / Yao, Meng / Richards, Elliott G / Goldberg, Jeffrey M

    Fertility and sterility

    2020  Volume 114, Issue 6, Page(s) 1207–1215

    Abstract: ... for blastocyst development, pregnancy, and live birth rate. Global (GB) medium (used without refreshment) and G ... formed morula sooner than their G-TL counterparts. The mean timing for start of blastulation did not ... <12 hours for proportionately more GB compared with G-TL-cultured embryos. Despite a higher rate ...

    Abstract Objective: To evaluate the efficacy of two different in vitro fertilization culture media for blastocyst development, pregnancy, and live birth rate. Global (GB) medium (used without refreshment) and G-TL medium (designed specifically for culture in time-lapse incubators) were compared.
    Design: Prospective randomized study of sibling embryo culture in two culture media.
    Setting: In vitro fertilization clinic.
    Patient(s): Women undergoing fresh or frozen cycles using autologous or donor oocytes.
    Intervention(s): None.
    Main outcome measure(s): The primary endpoints were implantation, pregnancy, and live birth rate (LBR) after single blastocyst transfer. Secondary endpoints included embryo morphokinetics, development of good-quality blastocysts, and euploidy rate.
    Result(s): Kinetic data from 10,768 sibling pronucleate embryos cultured in the EmbryoScope were compared. GB embryos initiated compaction earlier and formed morula sooner than their G-TL counterparts. The mean timing for start of blastulation did not differ. The interval between start of blastulation and time of blastocyst formation was observed to be <12 hours for proportionately more GB compared with G-TL-cultured embryos. Despite a higher rate of observed dysmorphisms in GB embryos, the euploidy rate among biopsied blastocysts did not differ between media. A total of 820 single-embryo transfer cycles were performed. Implantation rates were similar between media, independent of whether the embryo transferred was fresh (GB 58.7% vs. G-TL 61.7%) or frozen (GB 64.1% vs. G-TL 60.5%). Live birth rates were also not different. With GB medium, the LBR for fresh and frozen transfers was 54.2% and 53.1%, respectively, as compared with 51.1% and 50%, respectively, with G-TL.
    Conclusion(s): Uninterrupted culture in a time-lapse incubator without medium refreshment was well supported by both media tested. Differences in morphokinetics did not necessarily dictate the superiority of one media over the other. Both pregnancy and LBR were not significantly influenced by choice of culture medium. The euploidy rate was also independent of culture medium.
    MeSH term(s) Adult ; Blastocyst/metabolism ; Blastocyst/physiology ; Cryopreservation ; Culture Media/metabolism ; Embryo Culture Techniques ; Embryo Implantation ; Female ; Fertility ; Humans ; Infertility/diagnosis ; Infertility/physiopathology ; Infertility/therapy ; Kinetics ; Live Birth ; Pregnancy ; Pregnancy Rate ; Prospective Studies ; Single Embryo Transfer/adverse effects ; Sperm Injections, Intracytoplasmic/adverse effects ; Treatment Outcome
    Chemical Substances Culture Media
    Language English
    Publishing date 2020-08-26
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial
    ZDB-ID 80133-1
    ISSN 1556-5653 ; 0015-0282
    ISSN (online) 1556-5653
    ISSN 0015-0282
    DOI 10.1016/j.fertnstert.2020.06.049
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    Zs.A 73: Show issues Location:
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  9. Article ; Online: Escherichia coli "TatExpress" strains export several g/L human growth hormone to the periplasm by the Tat pathway.

    Guerrero Montero, Isabel / Richards, Kirsty L / Jawara, Chillel / Browning, Douglas F / Peswani, Amber R / Labrit, Mickael / Allen, Matthew / Aubry, Cedric / Davé, Emma / Humphreys, David P / Busby, Stephen J W / Robinson, Colin

    Biotechnology and bioengineering

    2019  Volume 116, Issue 12, Page(s) 3282–3291

    Abstract: ... that the yields of purified periplasmic hGH are 5.4 g/L culture whereas an enzyme-linked immunosorbent assay gave ... a figure of 2.39 g/L. Separate analysis of a TorA signal peptide linked to hGH construct lacking ...

    Abstract Escherichia coli is a heavily used platform for the production of biotherapeutic and other high-value proteins, and a favored strategy is to export the protein of interest to the periplasm to simplify downstream processing and facilitate disulfide bond formation. The Sec pathway is the standard means of transporting the target protein but it is unable to transport complex or rapidly folding proteins because the Sec system can only transport proteins in an unfolded state. The Tat system also operates to transport proteins to the periplasm, and it has significant potential as an alternative means of recombinant protein production because it transports fully folded proteins. Here, we have tested the Tat system's full potential for the production of biotherapeutics for the first time using fed-batch fermentation. We expressed human growth hormone (hGH) with a Tat signal peptide in E. coli W3110 "TatExpress" strains that contain elevated levels of the Tat apparatus. This construct contained four amino acids from TorA at the hGH N-terminus as well as the initiation methionine from hGH, which is removed in vivo. We show that the protein is efficiently exported to the periplasm during extended fed-batch fermentation, to the extent that it is by far the most abundant protein in the periplasm. The protein was shown to be homogeneous, disulfide bonded, and active. The bioassay showed that the yields of purified periplasmic hGH are 5.4 g/L culture whereas an enzyme-linked immunosorbent assay gave a figure of 2.39 g/L. Separate analysis of a TorA signal peptide linked to hGH construct lacking any additional amino acids likewise showed efficient export to the periplasm, although yields were approximately two-fold lower.
    MeSH term(s) Escherichia coli/genetics ; Escherichia coli/metabolism ; Human Growth Hormone/biosynthesis ; Human Growth Hormone/genetics ; Humans ; Periplasm/genetics ; Periplasm/metabolism ; Protein Folding ; Protein Sorting Signals ; Recombinant Fusion Proteins/biosynthesis ; Recombinant Fusion Proteins/genetics
    Chemical Substances Protein Sorting Signals ; Recombinant Fusion Proteins ; Human Growth Hormone (12629-01-5)
    Language English
    Publishing date 2019-09-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 280318-5
    ISSN 1097-0290 ; 0006-3592
    ISSN (online) 1097-0290
    ISSN 0006-3592
    DOI 10.1002/bit.27147
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  10. Article ; Online: Proof of Principle for a Novel Class of Antihypertensives That Target the Oxidative Activation of PKG Iα (Protein Kinase G Iα).

    Burgoyne, Joseph R / Prysyazhna, Oleksandra / Richards, Daniel A / Eaton, Philip

    Hypertension (Dallas, Tex. : 1979)

    2017  Volume 70, Issue 3, Page(s) 577–586

    Abstract: ... potential. Oxidants induce an interprotein disulfide in PKG Iα (protein kinase G Iα) at C42, which is ...

    Abstract Arterial hypertension continues to be a major health burden. Development of new antihypertensive drugs that engage vasodilatory mechanisms not harnessed by available therapies offer therapeutic potential. Oxidants induce an interprotein disulfide in PKG Iα (protein kinase G Iα) at C42, which is associated with its targeting and activation, resulting in vasodilation and blood pressure lowering. Consequently, we developed an assay and screened for electrophilic drugs that activate PKG Iα by selectively targeting C42, as such compounds have potential as novel antihypertensives with a mechanism of action that differs from current therapies. In this way, a drug that we termed G1 was identified, which targets C42 of PKG Iα to induce vasodilation of isolated resistance blood vessels and blood pressure lowering in a mouse model of angiotensin II-induced hypertension. In contrast, these antihypertensive effects were deficient in angiotensin II-induced hypertensive C42S PKG Iα knockin mice. These transgenic mice were engineered to have the reactive cysteinyl thiol replaced with a hydroxyl so that it cannot react with endogenous vasodilatory oxidants or electrophiles such as drug G1. These studies, therefore, provide validation of PKG Iα C42 as the target of G1, as well as proof-of-principle for a new class of antihypertensive drugs that have potential for further development for clinical use in humans.
    MeSH term(s) Animals ; Antihypertensive Agents/pharmacology ; Blood Pressure/drug effects ; Blood Pressure/physiology ; Cyclic GMP-Dependent Protein Kinase Type I/metabolism ; Disease Models, Animal ; Hypertension/drug therapy ; Hypertension/metabolism ; Hypertension/physiopathology ; Mice ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/metabolism ; Oxidation-Reduction/drug effects ; Treatment Outcome ; Vasodilation/drug effects ; Vasodilation/physiology
    Chemical Substances Antihypertensive Agents ; Cyclic GMP-Dependent Protein Kinase Type I (EC 2.7.11.12)
    Language English
    Publishing date 2017-07-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.117.09670
    Database MEDical Literature Analysis and Retrieval System OnLINE

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