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  1. Article: Silicon–Carbon Core–Shell Hollow Nanotubular Configuration High-Performance Lithium-Ion Anodes

    Gattu, Bharat / Epur Rigved / Jampani Prashanth H / Kuruba Ramalinga / Datta Moni Kanchan / Kumta Prashant N

    The Journal of Physical Chemistry C. 2017 May 11, v. 121, no. 18

    2017  

    Abstract: Silicon anode systems, due to their intrinsic high theoretical specific capacity, show tremendous potential in lithium ion batteries (LIBs). Unfortunately, commercial application still remains elusive due to the cycling-related colossal volume expansion ... ...

    Abstract Silicon anode systems, due to their intrinsic high theoretical specific capacity, show tremendous potential in lithium ion batteries (LIBs). Unfortunately, commercial application still remains elusive due to the cycling-related colossal volume expansion issues following Li alloying and dealloying. Herein, core–shell C@Si@C hollow nanotubes with optimal Si thickness (∼60 nm) showing no microstructural damage during lithiation and delithiation processes, have been developed as a stable anode for LIBs with low first-cycle irreversible loss (FIR) of ∼13% and high areal capacity (∼3 mAhcm–²) for the first time. The hollow Si nanotubes (h-SiNTs) have been generated via our previously reported high-throughput and recyclable, sacrificial MgO wire template fabrication approach. Generation of Si films of varying thickness by low-pressure thermal chemical vapor deposition (LPCVD) with subsequent etching yields h-SiNTs. Modification/optimization of the h-SiNT physical characteristics exhibit improved performance in LIBs. Carbon coating of optimized h-SiNTs further, yields core–shell h-SiNTs for the first time exhibiting not only low FIR loss of ∼13%, with a specific capacity of ∼1000 mA·h·g–¹ at discharge/charge currents of ∼1 A·g–¹ for over 120 cycles, but also a low fade rate of ∼0.072% loss per cycle.
    Keywords anodes ; carbon ; coatings ; lithium batteries ; magnesium oxide ; nanotubes ; physical chemistry ; silicon ; vapors
    Language English
    Dates of publication 2017-0511
    Size p. 9662-9671.
    Publishing place American Chemical Society
    Document type Article
    ISSN 1932-7455
    DOI 10.1021%2Facs.jpcc.7b00057
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Targeted delivery of nucleic-acid-based therapeutics to the pulmonary circulation.

    Kuruba, Ramalinga / Wilson, Annette / Gao, Xiang / Li, Song

    The AAPS journal

    2009  Volume 11, Issue 1, Page(s) 23–30

    Abstract: Targeted delivery of functional nucleic acids (genes and oligonucleotides) to pulmonary endothelium may become a novel therapy for the treatment of various types of lung diseases. It may also provide a new research tool to study the functions and ... ...

    Abstract Targeted delivery of functional nucleic acids (genes and oligonucleotides) to pulmonary endothelium may become a novel therapy for the treatment of various types of lung diseases. It may also provide a new research tool to study the functions and regulation of novel genes in pulmonary endothelium. Its success is largely dependent on the development of a vehicle that is capable of efficient pulmonary delivery with minimal toxicity. This review summarizes the recent progress that has been made in our laboratory along these research directions. Factors that affect pulmonary nucleic acids delivery are also discussed.
    MeSH term(s) Administration, Inhalation ; Animals ; Antigens, Surface/drug effects ; Cations/pharmacokinetics ; Dependovirus/genetics ; Drug Carriers/administration & dosage ; Drug Carriers/pharmacokinetics ; Drug Delivery Systems/methods ; Endothelial Cells/drug effects ; Genetic Therapy/methods ; Genetic Vectors/administration & dosage ; Genetic Vectors/pharmacokinetics ; Humans ; Injections, Intravenous ; Lipids/administration & dosage ; Lipids/pharmacokinetics ; Liposomes/administration & dosage ; Liposomes/pharmacokinetics ; Lung/blood supply ; Lung/cytology ; Mice ; Nucleic Acids/administration & dosage ; Nucleic Acids/pharmacokinetics ; Nucleic Acids/therapeutic use ; Oligonucleotides/administration & dosage ; Oligonucleotides/pharmacokinetics ; Oligonucleotides/therapeutic use ; Peptides/administration & dosage ; Peptides/pharmacokinetics ; Polymers/pharmacokinetics ; Pulmonary Circulation ; RNA, Small Interfering/administration & dosage ; RNA, Small Interfering/pharmacokinetics ; RNA, Small Interfering/therapeutic use
    Chemical Substances Antigens, Surface ; Cations ; Drug Carriers ; Lipids ; Liposomes ; Nucleic Acids ; Oligonucleotides ; Peptides ; Polymers ; RNA, Small Interfering
    Language English
    Publishing date 2009-01-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1550-7416
    ISSN (online) 1550-7416
    DOI 10.1208/s12248-008-9073-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Fluorine substituted (Mn,Ir)O2:F high performance solid solution oxygen evolution reaction electro-catalysts for PEM water electrolysis

    Ghadge, Shrinath Dattatray / Patel, Prasad Prakash / Datta, Moni Kanchan / Velikokhatnyi, Oleg I / Kuruba, Ramalinga / Shanthi, Pavithra M / Kumta, Prashant N

    RSC advances. 2017 Mar. 20, v. 7, no. 28

    2017  

    Abstract: Identification and development of high performance with reduced overpotential (i.e. reduced operating electricity cost) oxygen evolution reaction (OER) electrocatalysts for proton exchange membrane (PEM) based water electrolysis with ultra-low noble ... ...

    Abstract Identification and development of high performance with reduced overpotential (i.e. reduced operating electricity cost) oxygen evolution reaction (OER) electrocatalysts for proton exchange membrane (PEM) based water electrolysis with ultra-low noble metal content (i.e. reduced materials cost) is of significant interest for economic hydrogen production, thus increasing the commercialization potential of PEM water electrolysis. Accordingly, a novel electrocatalyst should exhibit low overpotential, excellent electrochemical activity and durability superior to state of the art noble metal based electro-catalysts (e.g. Pt, IrO2, RuO2). Herein, for the very first time to the best of our knowledge, exploiting first-principles theoretical calculations of the total energies and electronic structures, we have identified a reduced noble metal content fluorine doped solid solution of MnO2 and IrO2, denoted as (Mn1−xIrx)O2:F (x = 0.2, 0.3, 0.4), OER electrocatalyst system exhibiting lower overpotential and higher current density than the state of the art IrO2 and other previously reported systems for PEM water electrolysis. The doped solid solution displays an excellent electrochemical performance with a lowest reported onset potential to date of ∼1.35 V (vs. RHE), ∼80 mV lower than that of IrO2 (∼1.43 V vs. RHE) and ∼15 fold (x = 0.3 and 0.4) higher electrochemical activity compared to pure IrO2. In addition, the system displays excellent long term electrochemical durability, similar to that of IrO2 in harsh acidic OER operating conditions. Our study therefore demonstrates remarkable, ∼60–80% reduction in noble metal content along with lower overpotential and excellent electrochemical performance clearly demonstrating the potential of the (Mn1−xIrx)O2:F system as an OER electro-catalyst for PEM water electrolysis.
    Keywords catalysts ; commercialization ; durability ; electricity costs ; electrochemistry ; electrolysis ; fluorine ; hydrogen production ; manganese dioxide ; oxygen production
    Language English
    Dates of publication 2017-0320
    Size p. 17311-17324.
    Publishing place The Royal Society of Chemistry
    Document type Article
    ISSN 2046-2069
    DOI 10.1039/c6ra27354h
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Noble metal-free bifunctional oxygen evolution and oxygen reduction acidic media electro-catalysts.

    Patel, Prasad Prakash / Datta, Moni Kanchan / Velikokhatnyi, Oleg I / Kuruba, Ramalinga / Damodaran, Krishnan / Jampani, Prashanth / Gattu, Bharat / Shanthi, Pavithra Murugavel / Damle, Sameer S / Kumta, Prashant N

    Scientific reports

    2016  Volume 6, Page(s) 28367

    Abstract: Identification of low cost, highly active, durable completely noble metal-free electro-catalyst for oxygen reduction reaction (ORR) in proton exchange membrane (PEM) fuel cells, oxygen evolution reaction (OER) in PEM based water electrolysis and metal ... ...

    Abstract Identification of low cost, highly active, durable completely noble metal-free electro-catalyst for oxygen reduction reaction (ORR) in proton exchange membrane (PEM) fuel cells, oxygen evolution reaction (OER) in PEM based water electrolysis and metal air batteries remains one of the major unfulfilled scientific and technological challenges of PEM based acid mediated electro-catalysts. In contrast, several non-noble metals based electro-catalysts have been identified for alkaline and neutral medium water electrolysis and fuel cells. Herein we report for the very first time, F doped Cu1.5Mn1.5O4, identified by exploiting theoretical first principles calculations for ORR and OER in PEM based systems. The identified novel noble metal-free electro-catalyst showed similar onset potential (1.43 V for OER and 1 V for ORR vs RHE) to that of IrO2 and Pt/C, respectively. The system also displayed excellent electrochemical activity comparable to IrO2 for OER and Pt/C for ORR, respectively, along with remarkable long term stability for 6000 cycles in acidic media validating theory, while also displaying superior methanol tolerance and yielding recommended power densities in full cell configurations.
    Language English
    Publishing date 2016-07-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep28367
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Inhibition of endothelin-1-mediated contraction of hepatic stellate cells by FXR ligand.

    Li, Jiang / Kuruba, Ramalinga / Wilson, Annette / Gao, Xiang / Zhang, Yifei / Li, Song

    PloS one

    2010  Volume 5, Issue 11, Page(s) e13955

    Abstract: Activation of hepatic stellate cells (HSCs) plays an important role in the development of cirrhosis through the increased production of collagen and the enhanced contractile response to vasoactive mediators such as endothelin-1 (ET-1). The farnesoid X ... ...

    Abstract Activation of hepatic stellate cells (HSCs) plays an important role in the development of cirrhosis through the increased production of collagen and the enhanced contractile response to vasoactive mediators such as endothelin-1 (ET-1). The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidneys, adrenals, and intestine. FXR is also expressed in HSCs and activation of FXR in HSCs is associated with significant decreases in collagen production. However, little is known about the roles of FXR in the regulation of contraction of HSCs. We report in this study that treatment of quiescent HSCs with GW4064, a synthetic FXR agonist, significantly inhibited the HSC transdifferentiation, which was associated with an inhibition of the upregulation of ET-1 expression. These GW4064-treated cells also showed reduced contractile response to ET-1 in comparison to HSCs without GW4064 treatment. We have further shown that GW4064 treatment inhibited the ET-1-mediated contraction in fully activated HSCs. To elucidate the potential mechanism we showed that GW4064 inhibited ET-1-mediated activation of Rho/ROCK pathway in activated HSCs. Our studies unveiled a new mechanism that might contribute to the anti-cirrhotic effects of FXR ligands.
    MeSH term(s) Animals ; Blotting, Western ; Cell Shape/drug effects ; Cell Transdifferentiation/drug effects ; Cells, Cultured ; Endothelin-1/genetics ; Endothelin-1/metabolism ; Endothelin-1/pharmacology ; Gene Expression Regulation/drug effects ; Hepatic Stellate Cells/cytology ; Hepatic Stellate Cells/drug effects ; Hepatic Stellate Cells/metabolism ; Isoxazoles/pharmacology ; Male ; Microfilament Proteins/metabolism ; Phosphorylation/drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear/agonists ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/drug effects ; rho-Associated Kinases/metabolism
    Chemical Substances Endothelin-1 ; Isoxazoles ; Microfilament Proteins ; Receptors, Cytoplasmic and Nuclear ; farnesoid X-activated receptor (0C5V0MRU6P) ; moesin (144131-77-1) ; rho-Associated Kinases (EC 2.7.11.1) ; GW 4064 (SR225WUZ0H)
    Language English
    Publishing date 2010-11-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0013955
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Inhibition of endothelin-1-mediated contraction of hepatic stellate cells by FXR ligand.

    Jiang Li / Ramalinga Kuruba / Annette Wilson / Xiang Gao / Yifei Zhang / Song Li

    PLoS ONE, Vol 5, Iss 11, p e

    2010  Volume 13955

    Abstract: Activation of hepatic stellate cells (HSCs) plays an important role in the development of cirrhosis through the increased production of collagen and the enhanced contractile response to vasoactive mediators such as endothelin-1 (ET-1). The farnesoid X ... ...

    Abstract Activation of hepatic stellate cells (HSCs) plays an important role in the development of cirrhosis through the increased production of collagen and the enhanced contractile response to vasoactive mediators such as endothelin-1 (ET-1). The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidneys, adrenals, and intestine. FXR is also expressed in HSCs and activation of FXR in HSCs is associated with significant decreases in collagen production. However, little is known about the roles of FXR in the regulation of contraction of HSCs. We report in this study that treatment of quiescent HSCs with GW4064, a synthetic FXR agonist, significantly inhibited the HSC transdifferentiation, which was associated with an inhibition of the upregulation of ET-1 expression. These GW4064-treated cells also showed reduced contractile response to ET-1 in comparison to HSCs without GW4064 treatment. We have further shown that GW4064 treatment inhibited the ET-1-mediated contraction in fully activated HSCs. To elucidate the potential mechanism we showed that GW4064 inhibited ET-1-mediated activation of Rho/ROCK pathway in activated HSCs. Our studies unveiled a new mechanism that might contribute to the anti-cirrhotic effects of FXR ligands.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2010-11-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Chronic activation of FXR in transgenic mice caused perinatal toxicity and sensitized mice to cholesterol toxicity.

    Cheng, Qiuqiong / Inaba, Yuka / Lu, Peipei / Xu, Meishu / He, Jinhan / Zhao, Yueshui / Guo, Grace L / Kuruba, Ramalinga / de la Vega, Rona / Evans, Rhobert W / Li, Song / Xie, Wen

    Molecular endocrinology (Baltimore, Md.)

    2015  Volume 29, Issue 4, Page(s) 571–582

    Abstract: The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, ... ...

    Abstract The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage.
    MeSH term(s) Animals ; Bile Acids and Salts/metabolism ; Cholesterol/toxicity ; Diet, High-Fat ; Intestines/drug effects ; Intestines/metabolism ; Liver/drug effects ; Liver/metabolism ; Liver Diseases/metabolism ; Mice ; Mice, Transgenic ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Tumor Necrosis Factor/genetics ; Receptors, Tumor Necrosis Factor/metabolism ; TWEAK Receptor ; Vitamin A/blood ; Vitamin E/blood
    Chemical Substances Bile Acids and Salts ; Receptors, Cytoplasmic and Nuclear ; Receptors, Tumor Necrosis Factor ; TWEAK Receptor ; Tnfrsf12a protein, mouse ; farnesoid X-activated receptor ; Vitamin A (11103-57-4) ; Vitamin E (1406-18-4) ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2015-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 639167-9
    ISSN 1944-9917 ; 0888-8809
    ISSN (online) 1944-9917
    ISSN 0888-8809
    DOI 10.1210/me.2014-1337
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Polyhydroxylalkyleneamines: a class of hydrophilic cationic polymer-based gene transfer agents.

    Gao, Xiang / Kuruba, Ramalinga / Damodaran, Krishnan / Day, Billy W / Liu, Dexi / Li, Song

    Journal of controlled release : official journal of the Controlled Release Society

    2009  Volume 137, Issue 1, Page(s) 38–45

    Abstract: A new series of cationic polymers, poly[N,N-bis-(2-hydroxylpropyl) alkylalcoholamine-co-ethylenediamine] were synthesized by directly cross-linking several dichloro alkylating agents with ethylenediamine and its derivatives. Co-polymerization with ... ...

    Abstract A new series of cationic polymers, poly[N,N-bis-(2-hydroxylpropyl) alkylalcoholamine-co-ethylenediamine] were synthesized by directly cross-linking several dichloro alkylating agents with ethylenediamine and its derivatives. Co-polymerization with cystamine introduces biodegradable disulfide bonds to the polymer backbone. When tested on COS-1 cells, PHAs showed reduced cytotoxicity, broad polymer to DNA ratios, and enhanced transfection activity that was 2-9-fold better than that of polyethylenimine. Comparison studies also revealed several chemical and physical parameters related to the biological activities of these polymers. The length of the side chain groups affects both transfection activity and toxicity of the polymers; a side chain group of moderate size appeared to be optimal for both high transfection activity and low toxicity. Introduction of biodegradable disulfide bonds to the polymer backbone further enhanced transfection activity and reduced toxicity of the polymer. Fractionated PHAs with molecular weight of > or =5000 Da were equally effective but smaller polymers were ineffective in transfection. This flexible synthesis route enables the determination of key structural and physical parameters related to polymer activity and could aid further improvement of polymer-based transfection agents.
    MeSH term(s) Acid Phosphatase/analysis ; Alkylation ; Animals ; COS Cells ; Cations/chemistry ; Cations/pharmacology ; Cell Line ; Cell Survival/drug effects ; Cercopithecus aethiops ; Cricetinae ; Cross-Linking Reagents/pharmacology ; Disulfides/chemistry ; Ethylenediamines/chemistry ; Ethylenediamines/pharmacology ; Ethylenediamines/toxicity ; Gene Transfer Techniques ; Genes, Reporter ; Green Fluorescent Proteins/genetics ; HeLa Cells ; Humans ; Hydrogen-Ion Concentration ; Lethal Dose 50 ; Luciferases/genetics ; Molecular Structure ; Molecular Weight ; Polyamines/chemistry ; Polyamines/pharmacology ; Polyamines/toxicity ; Polyethyleneimine/chemistry ; Polyethyleneimine/pharmacology ; Polymers/chemistry ; Polymers/pharmacology ; Polymers/toxicity ; Transfection ; alpha-Galactosidase/genetics
    Chemical Substances Cations ; Cross-Linking Reagents ; Disulfides ; Ethylenediamines ; Polyamines ; Polymers ; enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9) ; ethylenediamine (60V9STC53F) ; Polyethyleneimine (9002-98-6) ; Luciferases (EC 1.13.12.-) ; Acid Phosphatase (EC 3.1.3.2) ; alpha-Galactosidase (EC 3.2.1.22)
    Language English
    Publishing date 2009-07-01
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2009.03.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Roles of microRNA-29a in the antifibrotic effect of farnesoid X receptor in hepatic stellate cells.

    Li, Jiang / Zhang, Yifei / Kuruba, Ramalinga / Gao, Xiang / Gandhi, Chandrashekhar R / Xie, Wen / Li, Song

    Molecular pharmacology

    2011  Volume 80, Issue 1, Page(s) 191–200

    Abstract: Liver fibrosis is a chronic disorder that is characterized by an alteration of the balance between fibrogenesis and fibrinolysis, which results in accumulation of excessive amounts of extracellular matrix (ECM) and distortion of the normal liver ... ...

    Abstract Liver fibrosis is a chronic disorder that is characterized by an alteration of the balance between fibrogenesis and fibrinolysis, which results in accumulation of excessive amounts of extracellular matrix (ECM) and distortion of the normal liver architecture. The activation and transformation of quiescent hepatic stellate cells (HSCs) into myofibroblast-like cells constitute a major mechanism for the increased production of ECM in the liver. The nuclear receptor farnesoid X receptor (FXR) shows potent antifibrotic activity in HSCs and protects animals in rodent models of liver fibrosis. However, the detailed mechanism remains incompletely understood. In this study, we report that treatment with 3-[2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]benzoic acid (GW4064), a synthetic FXR ligand, led to up-regulation of microRNA-29a (miR-29a) in HSCs isolated from wild-type mice, rats, and humans but not from FXR(-/-) mice. miR-29a seems to play an inhibitory role in the regulation of ECM production because of the following: 1) transfection of HSCs with miR-29a mimic resulted in drastic down-regulation of the mRNA expression of several genes that encode ECM proteins; and 2) miR-29a significantly inhibited the expression of a reporter expression plasmid that contains the 3'-untranslated region of the corresponding ECM genes. Our results suggest that miR-29a is a FXR target gene because miR-29a promoter activity was significantly increased by pharmacologic or genetic activation of FXR. Functional analysis of human miR-29a promoter identified an imperfect inverted repeat spaced by one nucleotide DNA motif, inverted repeat-1 (5'-AGGTCAcAGACCT-3'), as a likely FXR-responsive element that is involved in miR-29a regulation. Our study uncovers a new mechanism by which FXR negatively regulates the expression of ECM in HSCs.
    MeSH term(s) Animals ; Base Sequence ; Blotting, Western ; Chromatin Immunoprecipitation ; Humans ; Liver/metabolism ; Liver/pathology ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs/physiology ; Molecular Sequence Data ; Polymerase Chain Reaction ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear/metabolism
    Chemical Substances MIRN29a microRNA, human ; MicroRNAs ; Receptors, Cytoplasmic and Nuclear ; farnesoid X-activated receptor (0C5V0MRU6P)
    Language English
    Publishing date 2011-04-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 124034-1
    ISSN 1521-0111 ; 0026-895X
    ISSN (online) 1521-0111
    ISSN 0026-895X
    DOI 10.1124/mol.110.068247
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: A functional cross-talk between liver X receptor-α and constitutive androstane receptor links lipogenesis and xenobiotic responses.

    Zhai, Yonggong / Wada, Tara / Zhang, Bin / Khadem, Shaheen / Ren, Songrong / Kuruba, Ramalinga / Li, Song / Xie, Wen

    Molecular pharmacology

    2010  Volume 78, Issue 4, Page(s) 666–674

    Abstract: The liver X receptor (LXR) and constitutive androstane receptor (CAR) are two nuclear receptors postulated to have distinct functions. LXR is a sterol sensor that promotes lipogenesis, whereas CAR is a xenosensor that controls xenobiotic responses. Here, ...

    Abstract The liver X receptor (LXR) and constitutive androstane receptor (CAR) are two nuclear receptors postulated to have distinct functions. LXR is a sterol sensor that promotes lipogenesis, whereas CAR is a xenosensor that controls xenobiotic responses. Here, we show that LXRα and CAR are functionally related in vivo. Loss of CAR increased the expression of lipogenic LXR target genes, leading to increased hepatic triglyceride accumulation, whereas activation of CAR inhibited the expression of LXR target genes and LXR ligand-induced lipogenesis. On the other hand, a combined loss of LXR α and β increased the basal expression of xenobiotic CAR target genes, whereas activation of LXR inhibited the expression of CAR target genes and sensitized mice to xenobiotic toxicants. The mutual suppression between LXRα and CAR was also observed in cell culture and reporter gene assays. LXRα, like CAR, exhibited constitutive activity in the absence of an exogenously added ligand by recruiting nuclear receptor coactivators. Interestingly, although CAR competed with LXRα for coactivators, the constitutive activity and recruitment of coactivators was not required for CAR to suppress the activity of LXRα. In vivo chromatin immunoprecipitation assay showed that cotreatment of a CAR agonist compromised the LXR agonist responsive recruitment of LXRα to Srebp-1c, whereas an LXR agonist inhibited the CAR agonist-responsive recruitment of CAR to Cyp2b10. In conclusion, our results have revealed dual functions of LXRα and CAR in lipogenesis and xenobiotic responses, establishing a unique role of these two receptors in integrating xenobiotic and endobiotic homeostasis.
    MeSH term(s) Animals ; Cells, Cultured ; Female ; Lipogenesis/drug effects ; Lipogenesis/genetics ; Lipogenesis/physiology ; Liver X Receptors ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Orphan Nuclear Receptors/deficiency ; Orphan Nuclear Receptors/metabolism ; Orphan Nuclear Receptors/physiology ; Pyridines/pharmacology ; Receptor Cross-Talk/drug effects ; Receptor Cross-Talk/physiology ; Receptors, Cytoplasmic and Nuclear/deficiency ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Cytoplasmic and Nuclear/physiology ; Xenobiotics/metabolism ; Xenobiotics/pharmacology
    Chemical Substances Liver X Receptors ; Nr1h3 protein, mouse ; Orphan Nuclear Receptors ; Pyridines ; Receptors, Cytoplasmic and Nuclear ; Xenobiotics ; constitutive androstane receptor (438XLITDI3) ; 1,4-bis(2-(3,5-dichloropyridyloxy))benzene (76150-91-9)
    Language English
    Publishing date 2010-06-30
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 124034-1
    ISSN 1521-0111 ; 0026-895X
    ISSN (online) 1521-0111
    ISSN 0026-895X
    DOI 10.1124/mol.110.064618
    Database MEDical Literature Analysis and Retrieval System OnLINE

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