JP2011503207A - 循環系細胞におけるｐｉｍ−１活性を操作するための組成物および方法 - Google Patents
循環系細胞におけるｐｉｍ−１活性を操作するための組成物および方法 Download PDFInfo
- Publication number
- JP2011503207A JP2011503207A JP2010534249A JP2010534249A JP2011503207A JP 2011503207 A JP2011503207 A JP 2011503207A JP 2010534249 A JP2010534249 A JP 2010534249A JP 2010534249 A JP2010534249 A JP 2010534249A JP 2011503207 A JP2011503207 A JP 2011503207A
- Authority
- JP
- Japan
- Prior art keywords
- pim
- cell
- heart
- cells
- promoter
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 146
- 239000000203 mixture Substances 0.000 title claims abstract description 96
- 101001001642 Xenopus laevis Serine/threonine-protein kinase pim-3 Proteins 0.000 title claims description 473
- 230000000694 effects Effects 0.000 title claims description 84
- 210000000130 stem cell Anatomy 0.000 claims abstract description 134
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 103
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 103
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 102
- 230000000747 cardiac effect Effects 0.000 claims abstract description 65
- 210000002064 heart cell Anatomy 0.000 claims abstract description 62
- 230000006907 apoptotic process Effects 0.000 claims abstract description 51
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 43
- 206010021143 Hypoxia Diseases 0.000 claims abstract description 39
- 230000002708 enhancing effect Effects 0.000 claims abstract description 27
- 238000004519 manufacturing process Methods 0.000 claims abstract description 21
- 230000007954 hypoxia Effects 0.000 claims abstract description 17
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 claims abstract description 16
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 claims abstract description 16
- 230000001939 inductive effect Effects 0.000 claims abstract description 15
- 230000008929 regeneration Effects 0.000 claims abstract description 6
- 238000011069 regeneration method Methods 0.000 claims abstract description 6
- 210000004027 cell Anatomy 0.000 claims description 263
- 210000002216 heart Anatomy 0.000 claims description 209
- 230000014509 gene expression Effects 0.000 claims description 202
- 101000595531 Homo sapiens Serine/threonine-protein kinase pim-1 Proteins 0.000 claims description 125
- 239000013598 vector Substances 0.000 claims description 125
- 102100036077 Serine/threonine-protein kinase pim-1 Human genes 0.000 claims description 119
- 210000001519 tissue Anatomy 0.000 claims description 109
- 108091008611 Protein Kinase B Proteins 0.000 claims description 100
- 210000004413 cardiac myocyte Anatomy 0.000 claims description 92
- 210000000056 organ Anatomy 0.000 claims description 86
- 230000001965 increasing effect Effects 0.000 claims description 73
- 210000004165 myocardium Anatomy 0.000 claims description 65
- 210000004204 blood vessel Anatomy 0.000 claims description 61
- 208000010125 myocardial infarction Diseases 0.000 claims description 50
- 230000002018 overexpression Effects 0.000 claims description 46
- 206010061216 Infarction Diseases 0.000 claims description 43
- 230000007574 infarction Effects 0.000 claims description 43
- 206010020880 Hypertrophy Diseases 0.000 claims description 42
- 241000700605 Viruses Species 0.000 claims description 42
- 230000006378 damage Effects 0.000 claims description 42
- 238000011282 treatment Methods 0.000 claims description 42
- 210000000663 muscle cell Anatomy 0.000 claims description 38
- 241001465754 Metazoa Species 0.000 claims description 37
- 230000011664 signaling Effects 0.000 claims description 36
- 210000005003 heart tissue Anatomy 0.000 claims description 34
- 239000003981 vehicle Substances 0.000 claims description 34
- 102000004433 Proto-Oncogene Proteins c-pim-1 Human genes 0.000 claims description 33
- 108010017121 Proto-Oncogene Proteins c-pim-1 Proteins 0.000 claims description 33
- 210000005167 vascular cell Anatomy 0.000 claims description 32
- 239000002502 liposome Substances 0.000 claims description 31
- 150000001875 compounds Chemical class 0.000 claims description 30
- 230000004083 survival effect Effects 0.000 claims description 30
- 238000001727 in vivo Methods 0.000 claims description 29
- 230000002107 myocardial effect Effects 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 28
- 208000014674 injury Diseases 0.000 claims description 28
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 25
- 230000003293 cardioprotective effect Effects 0.000 claims description 25
- 201000010099 disease Diseases 0.000 claims description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 208000028867 ischemia Diseases 0.000 claims description 23
- 239000013603 viral vector Substances 0.000 claims description 23
- 208000027418 Wounds and injury Diseases 0.000 claims description 22
- 206010019280 Heart failures Diseases 0.000 claims description 21
- 230000006698 induction Effects 0.000 claims description 21
- 239000013612 plasmid Substances 0.000 claims description 19
- 108020004999 messenger RNA Proteins 0.000 claims description 18
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 claims description 17
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims description 17
- 102100037852 Insulin-like growth factor I Human genes 0.000 claims description 17
- 108700000711 bcl-X Proteins 0.000 claims description 17
- 102000055104 bcl-X Human genes 0.000 claims description 17
- 208000015181 infectious disease Diseases 0.000 claims description 17
- 230000026731 phosphorylation Effects 0.000 claims description 17
- 238000006366 phosphorylation reaction Methods 0.000 claims description 17
- 230000035755 proliferation Effects 0.000 claims description 17
- 238000001356 surgical procedure Methods 0.000 claims description 17
- 230000007755 survival signaling Effects 0.000 claims description 17
- 206010063837 Reperfusion injury Diseases 0.000 claims description 16
- 239000002105 nanoparticle Substances 0.000 claims description 16
- 102000040430 polynucleotide Human genes 0.000 claims description 15
- 108091033319 polynucleotide Proteins 0.000 claims description 15
- 239000002157 polynucleotide Substances 0.000 claims description 15
- 230000002265 prevention Effects 0.000 claims description 14
- 230000002792 vascular Effects 0.000 claims description 14
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 claims description 13
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 claims description 13
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 13
- 102000004127 Cytokines Human genes 0.000 claims description 12
- 108090000695 Cytokines Proteins 0.000 claims description 12
- 102000004058 Leukemia inhibitory factor Human genes 0.000 claims description 12
- 108090000581 Leukemia inhibitory factor Proteins 0.000 claims description 12
- 230000000735 allogeneic effect Effects 0.000 claims description 12
- 208000013875 Heart injury Diseases 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- 206010002660 Anoxia Diseases 0.000 claims description 10
- 241000976983 Anoxia Species 0.000 claims description 10
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 claims description 10
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 claims description 10
- 230000007953 anoxia Effects 0.000 claims description 10
- 230000002424 anti-apoptotic effect Effects 0.000 claims description 10
- 230000005779 cell damage Effects 0.000 claims description 10
- 208000018875 hypoxemia Diseases 0.000 claims description 10
- 230000006872 improvement Effects 0.000 claims description 10
- 230000001177 retroviral effect Effects 0.000 claims description 10
- 108010051583 Ventricular Myosins Proteins 0.000 claims description 9
- 230000007348 cell dedifferentiation Effects 0.000 claims description 9
- 230000001969 hypertrophic effect Effects 0.000 claims description 9
- 230000004048 modification Effects 0.000 claims description 9
- 238000012986 modification Methods 0.000 claims description 9
- 230000001172 regenerating effect Effects 0.000 claims description 9
- 230000008439 repair process Effects 0.000 claims description 9
- 206010061598 Immunodeficiency Diseases 0.000 claims description 8
- 208000029462 Immunodeficiency disease Diseases 0.000 claims description 8
- 239000003623 enhancer Substances 0.000 claims description 8
- 230000007813 immunodeficiency Effects 0.000 claims description 8
- 230000000302 ischemic effect Effects 0.000 claims description 8
- 210000003205 muscle Anatomy 0.000 claims description 8
- 238000002054 transplantation Methods 0.000 claims description 8
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 7
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 7
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 7
- 101100352234 Homo sapiens PIM1 gene Proteins 0.000 claims description 7
- 102100026925 Myosin regulatory light chain 2, ventricular/cardiac muscle isoform Human genes 0.000 claims description 7
- 101710105127 Myosin regulatory light chain 2, ventricular/cardiac muscle isoform Proteins 0.000 claims description 7
- 102000004987 Troponin T Human genes 0.000 claims description 7
- 108090001108 Troponin T Proteins 0.000 claims description 7
- 210000004504 adult stem cell Anatomy 0.000 claims description 7
- 210000004507 artificial chromosome Anatomy 0.000 claims description 7
- 210000004271 bone marrow stromal cell Anatomy 0.000 claims description 7
- 210000003038 endothelium Anatomy 0.000 claims description 7
- 210000004185 liver Anatomy 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 7
- 210000002460 smooth muscle Anatomy 0.000 claims description 7
- 210000000952 spleen Anatomy 0.000 claims description 7
- 208000007848 Alcoholism Diseases 0.000 claims description 6
- 208000006029 Cardiomegaly Diseases 0.000 claims description 6
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 claims description 6
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 claims description 6
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 230000032683 aging Effects 0.000 claims description 6
- 201000007930 alcohol dependence Diseases 0.000 claims description 6
- 230000037326 chronic stress Effects 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 210000002308 embryonic cell Anatomy 0.000 claims description 6
- 210000004700 fetal blood Anatomy 0.000 claims description 6
- 208000019622 heart disease Diseases 0.000 claims description 6
- 230000004054 inflammatory process Effects 0.000 claims description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 6
- 230000004792 oxidative damage Effects 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 238000007634 remodeling Methods 0.000 claims description 6
- 230000008733 trauma Effects 0.000 claims description 6
- 108010007734 bcl-Associated Death Protein Proteins 0.000 claims description 5
- 102000007348 bcl-Associated Death Protein Human genes 0.000 claims description 5
- 210000002798 bone marrow cell Anatomy 0.000 claims description 5
- 210000002826 placenta Anatomy 0.000 claims description 5
- 102000015696 Interleukins Human genes 0.000 claims description 4
- 108010063738 Interleukins Proteins 0.000 claims description 4
- 208000024248 Vascular System injury Diseases 0.000 claims description 4
- 208000012339 Vascular injury Diseases 0.000 claims description 4
- 210000001185 bone marrow Anatomy 0.000 claims description 4
- 229940124447 delivery agent Drugs 0.000 claims description 4
- 208000037906 ischaemic injury Diseases 0.000 claims description 4
- 230000014759 maintenance of location Effects 0.000 claims description 4
- 230000003076 paracrine Effects 0.000 claims description 4
- 239000003053 toxin Substances 0.000 claims description 4
- 231100000765 toxin Toxicity 0.000 claims description 4
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims description 4
- 208000019553 vascular disease Diseases 0.000 claims description 4
- 102000004877 Insulin Human genes 0.000 claims description 3
- 108090001061 Insulin Proteins 0.000 claims description 3
- 210000005260 human cell Anatomy 0.000 claims description 3
- 229940125396 insulin Drugs 0.000 claims description 3
- 208000037891 myocardial injury Diseases 0.000 claims description 3
- 230000000472 traumatic effect Effects 0.000 claims description 3
- 208000035143 Bacterial infection Diseases 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 2
- 230000003683 cardiac damage Effects 0.000 claims description 2
- 230000001146 hypoxic effect Effects 0.000 claims description 2
- 239000000411 inducer Substances 0.000 claims description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 2
- 230000005945 translocation Effects 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims 6
- 210000004556 brain Anatomy 0.000 claims 6
- 210000001508 eye Anatomy 0.000 claims 6
- 210000003734 kidney Anatomy 0.000 claims 6
- 210000004072 lung Anatomy 0.000 claims 6
- 210000004400 mucous membrane Anatomy 0.000 claims 6
- 210000005036 nerve Anatomy 0.000 claims 6
- 210000000496 pancreas Anatomy 0.000 claims 6
- 230000001953 sensory effect Effects 0.000 claims 6
- 210000002027 skeletal muscle Anatomy 0.000 claims 6
- 210000003491 skin Anatomy 0.000 claims 6
- 210000001032 spinal nerve Anatomy 0.000 claims 6
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims 2
- 230000004663 cell proliferation Effects 0.000 abstract description 12
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 57
- 241000699670 Mus sp. Species 0.000 description 45
- 108090000623 proteins and genes Proteins 0.000 description 40
- 238000003119 immunoblot Methods 0.000 description 32
- 238000002347 injection Methods 0.000 description 32
- 239000007924 injection Substances 0.000 description 32
- 102000004169 proteins and genes Human genes 0.000 description 30
- 230000007423 decrease Effects 0.000 description 28
- 238000009472 formulation Methods 0.000 description 28
- 235000018102 proteins Nutrition 0.000 description 27
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 26
- 230000006870 function Effects 0.000 description 25
- 210000000107 myocyte Anatomy 0.000 description 25
- 208000024891 symptom Diseases 0.000 description 24
- -1 PIM-1 Chemical compound 0.000 description 23
- 238000005259 measurement Methods 0.000 description 23
- 108091000080 Phosphotransferase Proteins 0.000 description 22
- 230000000004 hemodynamic effect Effects 0.000 description 22
- 102000020233 phosphotransferase Human genes 0.000 description 22
- 230000002829 reductive effect Effects 0.000 description 22
- 230000002861 ventricular Effects 0.000 description 22
- 241000701161 unidentified adenovirus Species 0.000 description 21
- 230000001404 mediated effect Effects 0.000 description 20
- 230000009261 transgenic effect Effects 0.000 description 20
- 230000003612 virological effect Effects 0.000 description 20
- 239000000243 solution Substances 0.000 description 19
- 102400000686 Endothelin-1 Human genes 0.000 description 18
- 101800004490 Endothelin-1 Proteins 0.000 description 18
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- 229940079593 drug Drugs 0.000 description 15
- 210000004940 nucleus Anatomy 0.000 description 15
- 239000002245 particle Substances 0.000 description 15
- 108090000765 processed proteins & peptides Proteins 0.000 description 15
- 230000004044 response Effects 0.000 description 15
- 230000001225 therapeutic effect Effects 0.000 description 15
- 108700019146 Transgenes Proteins 0.000 description 14
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 14
- 238000000338 in vitro Methods 0.000 description 14
- 239000006166 lysate Substances 0.000 description 14
- 230000001105 regulatory effect Effects 0.000 description 14
- 108010029485 Protein Isoforms Proteins 0.000 description 13
- 102000001708 Protein Isoforms Human genes 0.000 description 13
- 229960004679 doxorubicin Drugs 0.000 description 13
- 230000012010 growth Effects 0.000 description 13
- 230000004217 heart function Effects 0.000 description 13
- 238000002372 labelling Methods 0.000 description 13
- 230000001681 protective effect Effects 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 230000004913 activation Effects 0.000 description 12
- 230000001640 apoptogenic effect Effects 0.000 description 12
- 238000010361 transduction Methods 0.000 description 12
- 230000026683 transduction Effects 0.000 description 12
- 208000031229 Cardiomyopathies Diseases 0.000 description 11
- 108020004705 Codon Proteins 0.000 description 11
- 230000030833 cell death Effects 0.000 description 11
- 150000002632 lipids Chemical class 0.000 description 11
- 235000002639 sodium chloride Nutrition 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 10
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 10
- KPKZJLCSROULON-QKGLWVMZSA-N Phalloidin Chemical compound N1C(=O)[C@@H]([C@@H](O)C)NC(=O)[C@H](C)NC(=O)[C@H](C[C@@](C)(O)CO)NC(=O)[C@H](C2)NC(=O)[C@H](C)NC(=O)[C@@H]3C[C@H](O)CN3C(=O)[C@@H]1CSC1=C2C2=CC=CC=C2N1 KPKZJLCSROULON-QKGLWVMZSA-N 0.000 description 10
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 10
- 229930006000 Sucrose Natural products 0.000 description 10
- 239000013543 active substance Substances 0.000 description 10
- 230000003247 decreasing effect Effects 0.000 description 10
- 239000005720 sucrose Substances 0.000 description 10
- 229960004793 sucrose Drugs 0.000 description 10
- 101100297651 Mus musculus Pim2 gene Proteins 0.000 description 9
- 230000035508 accumulation Effects 0.000 description 9
- 238000009825 accumulation Methods 0.000 description 9
- 230000037396 body weight Effects 0.000 description 9
- 230000007774 longterm Effects 0.000 description 9
- 230000004942 nuclear accumulation Effects 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- 201000008752 progressive muscular atrophy Diseases 0.000 description 9
- 238000011084 recovery Methods 0.000 description 9
- 238000004904 shortening Methods 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 230000000638 stimulation Effects 0.000 description 9
- 238000011830 transgenic mouse model Methods 0.000 description 9
- 210000005166 vasculature Anatomy 0.000 description 9
- 206010016654 Fibrosis Diseases 0.000 description 8
- 241000699660 Mus musculus Species 0.000 description 8
- 238000004624 confocal microscopy Methods 0.000 description 8
- 230000001419 dependent effect Effects 0.000 description 8
- 238000011156 evaluation Methods 0.000 description 8
- 230000004761 fibrosis Effects 0.000 description 8
- 238000001415 gene therapy Methods 0.000 description 8
- PTVWPYVOOKLBCG-ZDUSSCGKSA-N levodropropizine Chemical compound C1CN(C[C@H](O)CO)CCN1C1=CC=CC=C1 PTVWPYVOOKLBCG-ZDUSSCGKSA-N 0.000 description 8
- 239000012528 membrane Substances 0.000 description 8
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 8
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 7
- 102400001282 Atrial natriuretic peptide Human genes 0.000 description 7
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 7
- 108090000315 Protein Kinase C Proteins 0.000 description 7
- 102000003923 Protein Kinase C Human genes 0.000 description 7
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 7
- 230000005754 cellular signaling Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 108700004025 env Genes Proteins 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 230000002779 inactivation Effects 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 238000011068 loading method Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 241000713666 Lentivirus Species 0.000 description 6
- 108700020796 Oncogene Proteins 0.000 description 6
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 230000005961 cardioprotection Effects 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 230000002950 deficient Effects 0.000 description 6
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 6
- 229960003957 dexamethasone Drugs 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 6
- 101150030339 env gene Proteins 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 229930195729 fatty acid Natural products 0.000 description 6
- 150000004665 fatty acids Chemical class 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 230000001976 improved effect Effects 0.000 description 6
- 238000011813 knockout mouse model Methods 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 238000011002 quantification Methods 0.000 description 6
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N quercetagetin Chemical compound C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 230000010410 reperfusion Effects 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 230000001629 suppression Effects 0.000 description 6
- 239000002562 thickening agent Substances 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 241001430294 unidentified retrovirus Species 0.000 description 6
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 5
- 102000007469 Actins Human genes 0.000 description 5
- 108010085238 Actins Proteins 0.000 description 5
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 5
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 5
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 5
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 5
- 229920000084 Gum arabic Polymers 0.000 description 5
- 108010009711 Phalloidine Proteins 0.000 description 5
- 229940122907 Phosphatase inhibitor Drugs 0.000 description 5
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 5
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 5
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 5
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 5
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 5
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 5
- 235000010489 acacia gum Nutrition 0.000 description 5
- 239000003963 antioxidant agent Substances 0.000 description 5
- 235000006708 antioxidants Nutrition 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 5
- 239000003086 colorant Substances 0.000 description 5
- 230000001447 compensatory effect Effects 0.000 description 5
- 230000008828 contractile function Effects 0.000 description 5
- 230000001086 cytosolic effect Effects 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 5
- 102000053248 human PIM1 Human genes 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 210000005240 left ventricle Anatomy 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 210000003632 microfilament Anatomy 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 5
- 102000005681 phospholamban Human genes 0.000 description 5
- 108010059929 phospholamban Proteins 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 230000003827 upregulation Effects 0.000 description 5
- VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 description 4
- 244000215068 Acacia senegal Species 0.000 description 4
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 4
- 101100297652 Coturnix japonica PIM3 gene Proteins 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 4
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 4
- 108091061960 Naked DNA Proteins 0.000 description 4
- 206010028851 Necrosis Diseases 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000000711 cancerogenic effect Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 231100000315 carcinogenic Toxicity 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 238000000942 confocal micrograph Methods 0.000 description 4
- 210000004351 coronary vessel Anatomy 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 235000003599 food sweetener Nutrition 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000007972 injectable composition Substances 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000003068 molecular probe Substances 0.000 description 4
- 230000017074 necrotic cell death Effects 0.000 description 4
- 238000005457 optimization Methods 0.000 description 4
- 239000012188 paraffin wax Substances 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 235000010356 sorbitol Nutrition 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 239000003765 sweetening agent Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 3
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 3
- 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 3
- 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 3
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 3
- 102000003952 Caspase 3 Human genes 0.000 description 3
- 108090000397 Caspase 3 Proteins 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 108700010070 Codon Usage Proteins 0.000 description 3
- 206010010144 Completed suicide Diseases 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 102100031690 Erythroid transcription factor Human genes 0.000 description 3
- 101710100588 Erythroid transcription factor Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 231100000002 MTT assay Toxicity 0.000 description 3
- 238000000134 MTT assay Methods 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 241000713883 Myeloproliferative sarcoma virus Species 0.000 description 3
- 241000288906 Primates Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 3
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 3
- 241000700584 Simplexvirus Species 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 229920001615 Tragacanth Polymers 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 238000000540 analysis of variance Methods 0.000 description 3
- 230000002236 anti-hypertrophic effect Effects 0.000 description 3
- 210000000709 aorta Anatomy 0.000 description 3
- 206010002906 aortic stenosis Diseases 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 210000000748 cardiovascular system Anatomy 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 239000002771 cell marker Substances 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000010339 dilation Effects 0.000 description 3
- 238000002592 echocardiography Methods 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 229960005309 estradiol Drugs 0.000 description 3
- 229930182833 estradiol Natural products 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 238000012224 gene deletion Methods 0.000 description 3
- 230000003394 haemopoietic effect Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000004005 microsphere Substances 0.000 description 3
- 230000002438 mitochondrial effect Effects 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 230000004224 protection Effects 0.000 description 3
- 108010083755 proto-oncogene proteins pim Proteins 0.000 description 3
- 239000012723 sample buffer Substances 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 235000006491 Acacia senegal Nutrition 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 102000051485 Bcl-2 family Human genes 0.000 description 2
- 108700038897 Bcl-2 family Proteins 0.000 description 2
- 102100026189 Beta-galactosidase Human genes 0.000 description 2
- 238000009010 Bradford assay Methods 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 2
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- 206010011906 Death Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000713730 Equine infectious anemia virus Species 0.000 description 2
- 241000713800 Feline immunodeficiency virus Species 0.000 description 2
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 2
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108091005461 Nucleic proteins Proteins 0.000 description 2
- 239000012828 PI3K inhibitor Substances 0.000 description 2
- 101800004021 PP2-A Proteins 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 2
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 2
- 101710149951 Protein Tat Proteins 0.000 description 2
- 102000052575 Proto-Oncogene Human genes 0.000 description 2
- 108700020978 Proto-Oncogene Proteins 0.000 description 2
- 241000713311 Simian immunodeficiency virus Species 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 2
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 2
- 208000026062 Tissue disease Diseases 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
- 102000003672 Tropomodulin Human genes 0.000 description 2
- 108090000089 Tropomodulin Proteins 0.000 description 2
- 241000713325 Visna/maedi virus Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000009692 acute damage Effects 0.000 description 2
- 230000003044 adaptive effect Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000035578 autophosphorylation Effects 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000013611 chromosomal DNA Substances 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000011260 co-administration Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007123 defense Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 108010027225 gag-pol Fusion Proteins Proteins 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 230000002390 hyperplastic effect Effects 0.000 description 2
- 230000005965 immune activity Effects 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 229940047122 interleukins Drugs 0.000 description 2
- 238000000021 kinase assay Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 230000034701 macropinocytosis Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 210000000723 mammalian artificial chromosome Anatomy 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000009456 molecular mechanism Effects 0.000 description 2
- 229940042880 natural phospholipid Drugs 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000030648 nucleus localization Effects 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 2
- 229960001802 phenylephrine Drugs 0.000 description 2
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 230000006659 positive regulation of apoptotic process Effects 0.000 description 2
- 230000007542 postnatal development Effects 0.000 description 2
- 230000000861 pro-apoptotic effect Effects 0.000 description 2
- 230000001566 pro-viral effect Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 210000001908 sarcoplasmic reticulum Anatomy 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000013605 shuttle vector Substances 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000012439 solid excipient Substances 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 241000894007 species Species 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 229920001059 synthetic polymer Polymers 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- 208000037816 tissue injury Diseases 0.000 description 2
- 229930003799 tocopherol Natural products 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 231100000164 trypan blue assay Toxicity 0.000 description 2
- 238000013042 tunel staining Methods 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000000341 volatile oil Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- DFUSDJMZWQVQSF-XLGIIRLISA-N (2r)-2-methyl-2-[(4r,8r)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-ol Chemical class OC1=CC=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 DFUSDJMZWQVQSF-XLGIIRLISA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- GJJVAFUKOBZPCB-ZGRPYONQSA-N (r)-3,4-dihydro-2-methyl-2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-2h-1-benzopyran-6-ol Chemical class OC1=CC=C2OC(CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1 GJJVAFUKOBZPCB-ZGRPYONQSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- NEWKHUASLBMWRE-UHFFFAOYSA-N 2-methyl-6-(phenylethynyl)pyridine Chemical compound CC1=CC=CC(C#CC=2C=CC=CC=2)=N1 NEWKHUASLBMWRE-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 108091006112 ATPases Proteins 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 230000007730 Akt signaling Effects 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108700031308 Antennapedia Homeodomain Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 235000003911 Arachis Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- JEBFVOLFMLUKLF-IFPLVEIFSA-N Astaxanthin Natural products CC(=C/C=C/C(=C/C=C/C1=C(C)C(=O)C(O)CC1(C)C)/C)C=CC=C(/C)C=CC=C(/C)C=CC2=C(C)C(=O)C(O)CC2(C)C JEBFVOLFMLUKLF-IFPLVEIFSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000713756 Caprine arthritis encephalitis virus Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010007558 Cardiac failure chronic Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 208000001778 Coronary Occlusion Diseases 0.000 description 1
- 206010011086 Coronary artery occlusion Diseases 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 101710132484 Cytokine-inducible SH2-containing protein Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 238000011771 FVB mouse Methods 0.000 description 1
- 241000700662 Fowlpox virus Species 0.000 description 1
- 102000016669 GATA1 Transcription Factor Human genes 0.000 description 1
- 108010028165 GATA1 Transcription Factor Proteins 0.000 description 1
- 229920002148 Gellan gum Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 241000175212 Herpesvirales Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 230000004163 JAK-STAT signaling pathway Effects 0.000 description 1
- 229920000161 Locust bean gum Polymers 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 102000005604 Myosin Heavy Chains Human genes 0.000 description 1
- 108010084498 Myosin Heavy Chains Proteins 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229940116355 PI3 kinase inhibitor Drugs 0.000 description 1
- 102000042867 PIM family Human genes 0.000 description 1
- 108091082273 PIM family Proteins 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 102220489127 Phosphatidylinositol transfer protein alpha isoform_K67M_mutation Human genes 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000023146 Pre-existing disease Diseases 0.000 description 1
- 241000713711 Primate lentivirus group Species 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 239000004792 Prolene Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000006478 Protein Phosphatase 2 Human genes 0.000 description 1
- 108010058956 Protein Phosphatase 2 Proteins 0.000 description 1
- 108010087776 Proto-Oncogene Proteins c-myb Proteins 0.000 description 1
- 102000009096 Proto-Oncogene Proteins c-myb Human genes 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 102000001712 STAT5 Transcription Factor Human genes 0.000 description 1
- 108010029477 STAT5 Transcription Factor Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 101710185500 Small t antigen Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 101710192266 Tegument protein VP22 Proteins 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 108700029229 Transcriptional Regulatory Elements Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 102000005937 Tropomyosin Human genes 0.000 description 1
- 108010030743 Tropomyosin Proteins 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 238000010162 Tukey test Methods 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108010087302 Viral Structural Proteins Proteins 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- ZKHQWZAMYRWXGA-KNYAHOBESA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] dihydroxyphosphoryl hydrogen phosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)O[32P](O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KNYAHOBESA-N 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000012197 amplification kit Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 230000005756 apoptotic signaling Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000013793 astaxanthin Nutrition 0.000 description 1
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 description 1
- 239000001168 astaxanthin Substances 0.000 description 1
- 229940022405 astaxanthin Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000009787 cardiac fibrosis Effects 0.000 description 1
- 229940045200 cardioprotective agent Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229920006317 cationic polymer Polymers 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000027902 cell growth involved in cardiac muscle cell development Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000006041 cell recruitment Effects 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000010226 confocal imaging Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 210000000555 contractile cell Anatomy 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 229940126513 cyclase activator Drugs 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 101150097231 eg gene Proteins 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 108090000062 ficolin Proteins 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000011773 genetically engineered mouse model Methods 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000008202 granule composition Substances 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000010185 immunofluorescence analysis Methods 0.000 description 1
- 238000010820 immunofluorescence microscopy Methods 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000012606 in vitro cell culture Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 102000002467 interleukin receptors Human genes 0.000 description 1
- 108010093036 interleukin receptors Proteins 0.000 description 1
- 210000005061 intracellular organelle Anatomy 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 235000010420 locust bean gum Nutrition 0.000 description 1
- 239000000711 locust bean gum Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 101150024228 mdm2 gene Proteins 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 239000006082 mold release agent Substances 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 238000007491 morphometric analysis Methods 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 210000002894 multi-fate stem cell Anatomy 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 210000003098 myoblast Anatomy 0.000 description 1
- 230000010016 myocardial function Effects 0.000 description 1
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- QNDVLZJODHBUFM-WFXQOWMNSA-N okadaic acid Chemical compound C([C@H](O1)[C@H](C)/C=C/[C@H]2CC[C@@]3(CC[C@H]4O[C@@H](C([C@@H](O)[C@@H]4O3)=C)[C@@H](O)C[C@H](C)[C@@H]3[C@@H](CC[C@@]4(OCCCC4)O3)C)O2)C(C)=C[C@]21O[C@H](C[C@@](C)(O)C(O)=O)CC[C@H]2O QNDVLZJODHBUFM-WFXQOWMNSA-N 0.000 description 1
- VEFJHAYOIAAXEU-UHFFFAOYSA-N okadaic acid Natural products CC(CC(O)C1OC2CCC3(CCC(O3)C=CC(C)C4CC(=CC5(OC(CC(C)(O)C(=O)O)CCC5O)O4)C)OC2C(O)C1C)C6OC7(CCCCO7)CCC6C VEFJHAYOIAAXEU-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 1
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000017363 positive regulation of growth Effects 0.000 description 1
- 230000009596 postnatal growth Effects 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 208000009305 pseudorabies Diseases 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000021014 regulation of cell growth Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000001718 repressive effect Effects 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 108010038196 saccharide-binding proteins Proteins 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 238000009168 stem cell therapy Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 210000000779 thoracic wall Anatomy 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 125000002640 tocopherol group Chemical class 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- 229930003802 tocotrienol Natural products 0.000 description 1
- 239000011731 tocotrienol Substances 0.000 description 1
- 229940068778 tocotrienols Drugs 0.000 description 1
- 235000019148 tocotrienols Nutrition 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012301 transgenic model Methods 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 210000000605 viral structure Anatomy 0.000 description 1
- 150000003712 vitamin E derivatives Chemical class 0.000 description 1
- QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 description 1
- QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/45—Transferases (2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/11—Protein-serine/threonine kinases (2.7.11)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/12—Dual-specificity kinases (2.7.12)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Cell Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Vascular Medicine (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US98875307P | 2007-11-16 | 2007-11-16 | |
| US9169808P | 2008-08-25 | 2008-08-25 | |
| PCT/US2008/083693 WO2009065080A1 (en) | 2007-11-16 | 2008-11-14 | Compositions and method for manipulating pim-1 activity in circulatory system cells |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014154915A Division JP5795670B2 (ja) | 2007-11-16 | 2014-07-30 | 循環系細胞におけるｐｉｍ−１活性を操作するための組成物および方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011503207A true JP2011503207A (ja) | 2011-01-27 |
| JP2011503207A5 JP2011503207A5 (enExample) | 2012-01-05 |
Family
ID=40639186
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010534249A Pending JP2011503207A (ja) | 2007-11-16 | 2008-11-14 | 循環系細胞におけるｐｉｍ−１活性を操作するための組成物および方法 |
| JP2014154915A Expired - Fee Related JP5795670B2 (ja) | 2007-11-16 | 2014-07-30 | 循環系細胞におけるｐｉｍ−１活性を操作するための組成物および方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014154915A Expired - Fee Related JP5795670B2 (ja) | 2007-11-16 | 2014-07-30 | 循環系細胞におけるｐｉｍ−１活性を操作するための組成物および方法 |
Country Status (5)
| Country | Link |
|---|---|
| US (5) | US8617534B2 (enExample) |
| EP (1) | EP2209889B1 (enExample) |
| JP (2) | JP2011503207A (enExample) |
| CA (1) | CA2705862C (enExample) |
| WO (1) | WO2009065080A1 (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6562632B2 (ja) * | 2012-02-14 | 2019-08-21 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 心血管疾患および他の状態のためのパラクリン遺伝子の全身送達および制御された発現 |
| EP2943485B1 (en) | 2013-01-14 | 2017-09-20 | Incyte Holdings Corporation | Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors |
| TWI662030B (zh) | 2013-01-15 | 2019-06-11 | 英塞特控股公司 | 適用作ｐｉｍ激酶抑制劑之噻唑甲醯胺及吡啶甲醯胺化合物 |
| US9556197B2 (en) | 2013-08-23 | 2017-01-31 | Incyte Corporation | Furo- and thieno-pyridine carboxamide compounds useful as pim kinase inhibitors |
| US9580418B2 (en) | 2014-07-14 | 2017-02-28 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors |
| WO2016010897A1 (en) | 2014-07-14 | 2016-01-21 | Incyte Corporation | Bicyclic heteroaromatic carboxamide compounds useful as pim kinase inhibitors |
| WO2016196244A1 (en) | 2015-05-29 | 2016-12-08 | Incyte Corporation | Pyridineamine compounds useful as pim kinase inhibitors |
| AR105967A1 (es) | 2015-09-09 | 2017-11-29 | Incyte Corp | Sales de un inhibidor de pim quinasa |
| WO2017059251A1 (en) | 2015-10-02 | 2017-04-06 | Incyte Corporation | Heterocyclic compounds useful as pim kinase inhibitors |
| WO2018232323A1 (en) | 2017-06-16 | 2018-12-20 | Avery Therapeutics, Inc. | Three dimensional tissue compositions and methods of use |
| TW201924683A (zh) | 2017-12-08 | 2019-07-01 | 美商英塞特公司 | 用於治療骨髓增生性贅瘤的低劑量組合療法 |
| CN108913655B (zh) * | 2018-07-16 | 2022-07-15 | 浙江大学 | 基于多能干细胞技术建立“人源性”心肌肥大模型的方法 |
| WO2020081604A2 (en) * | 2018-10-15 | 2020-04-23 | Avery Therapeutics, Inc. | Cell-free compositions and methods for restoration or enhancement of tissue function |
| FI4103214T3 (fi) | 2020-02-13 | 2026-07-03 | Tenaya Therapeutics Inc | Geeniterapian vektorit sydänsairauden hoitoon |
| KR102860173B1 (ko) * | 2020-09-04 | 2025-09-15 | 데쿠세리아루즈 가부시키가이샤 | 도전성 적층체 및 이것을 사용한 광학 장치, 도전성 적층체의 제조 방법 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004521108A (ja) * | 2001-01-18 | 2004-07-15 | ザ ボード オブ トラスティーズ オブ ザ リーランド スタンフォード ジュニア ユニバーシティ | δＰＫＣの活性化および阻害のためのペプチド |
| WO2004113367A1 (ja) * | 2003-06-24 | 2004-12-29 | Keio University | アポトーシス抑制活性を有するペプチド |
| JP2005501802A (ja) * | 2001-01-23 | 2005-01-20 | ボストン サイエンティフィック コーポレイション | 虚血心筋を処置するための限局性心筋注入方法 |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5217879A (en) | 1989-01-12 | 1993-06-08 | Washington University | Infectious Sindbis virus vectors |
| US20040132190A1 (en) | 1995-02-28 | 2004-07-08 | The Regents Of The University Of California | Gene therapy for myocardial ischemia |
| US5716928A (en) | 1995-06-07 | 1998-02-10 | Avmax, Inc. | Use of essential oils to increase bioavailability of oral pharmaceutical compounds |
| US5858401A (en) | 1996-01-22 | 1999-01-12 | Sidmak Laboratories, Inc. | Pharmaceutical composition for cyclosporines |
| US6007839A (en) | 1996-02-16 | 1999-12-28 | The Liposome Company, Inc. | Preparation of pharmaceutical compositions containing etherlipid-containing multiple lipid liposomes |
| US5869037A (en) * | 1996-06-26 | 1999-02-09 | Cornell Research Foundation, Inc. | Adenoviral-mediated gene transfer to adipocytes |
| AU741931B2 (en) * | 1996-09-05 | 2001-12-13 | Collateral Therapeutics, Inc. | Gene therapy for congestive heart failure |
| PT904392E (pt) | 1996-10-17 | 2001-06-29 | Oxford Biomedica Ltd | Vectores retrovirais |
| US7198784B2 (en) | 1996-10-17 | 2007-04-03 | Oxford Biomedica (Uk) Limited | Retroviral vectors |
| WO1999032646A1 (en) | 1997-12-22 | 1999-07-01 | Oxford Biomedica (Uk) Limited | Equine infectious anaemia virus (eiav) based |
| US6924123B2 (en) | 1996-10-29 | 2005-08-02 | Oxford Biomedica (Uk) Limited | Lentiviral LTR-deleted vector |
| US6630137B1 (en) | 1997-04-28 | 2003-10-07 | Eli Lilly And Company | Activated protein C formulations |
| CN1247788C (zh) | 1997-05-13 | 2006-03-29 | 北卡罗来纳-查佩尔山大学 | 基于慢病毒的基因转移载体 |
| CN1261791A (zh) | 1997-07-02 | 2000-08-02 | Sdg有限公司 | 诊断或治疗用途的靶向脂质体构建物 |
| ATE298371T1 (de) | 1997-09-24 | 2005-07-15 | Univ California | Nicht-primaten lentivirale vektoren und verpackungssysteme |
| US6943153B1 (en) | 1999-03-15 | 2005-09-13 | The Regents Of The University Of California | Use of recombinant gene delivery vectors for treating or preventing diseases of the eye |
| US6867348B1 (en) * | 1999-12-16 | 2005-03-15 | Xenogen Corporation | Methods and compositions for screening for angiogenesis modulating compounds |
| US7122181B2 (en) | 2000-12-19 | 2006-10-17 | Research Development Foundation | Lentiviral vector-mediated gene transfer and uses thereof |
| US20030003582A1 (en) | 2001-05-08 | 2003-01-02 | Tranzyme, Inc. | Trans-viral vector mediated gene transfer to the retina |
| US7732199B2 (en) * | 2001-07-12 | 2010-06-08 | Geron Corporation | Process for making transplantable cardiomyocytes from human embryonic stem cells |
| US7671010B2 (en) | 2002-08-30 | 2010-03-02 | The Board Of Regents Of The University Of Texas System | Compositions and methods of use of targeting peptides for diagnosis and therapy of human cancer |
| CA2462628C (en) | 2001-10-02 | 2019-08-20 | Institut Clayton De La Recherche | Restricted expression lentiviral vectors |
| WO2004044142A2 (en) * | 2002-11-05 | 2004-05-27 | The Brigham And Women's Hospital, Inc. | Mesenchymal stem cells and methods of use thereof |
| WO2004090158A1 (ja) * | 2003-04-03 | 2004-10-21 | Oncorex, Inc. | 医薬品 |
| US7135339B2 (en) | 2003-11-20 | 2006-11-14 | University Of Iowa Research Foundation | Methods for producing and using in vivo pseudotyped retroviruses using envelope glycoproteins from lymphocytic choriomeningitis virus (LCMV) |
| KR20060123384A (ko) | 2003-12-24 | 2006-12-01 | 가부시키가이샤 엘티티 바이오파마 | 약물을 함유하는 나노 입자 및 그 제조 방법, 그리고 당해나노 입자로 이루어지는 비경구 투여용 제제 |
| JP2007526322A (ja) | 2004-03-02 | 2007-09-13 | マサチューセッツ インスティテュート オブ テクノロジー | ナノセル薬物送達系 |
| US20070082042A1 (en) | 2004-08-06 | 2007-04-12 | Deok-Hoon Park | Multiple-layered liposome and preparation method thereof |
| US20080267921A1 (en) * | 2004-11-08 | 2008-10-30 | Johns Hopkins University | Cardiac Stem Cells |
| CA2609937A1 (en) * | 2005-05-27 | 2006-11-30 | The Hospital For Sick Children | Modulation of the integrin linked kinase signaling pathway to promote cardiac cell proliferation and self-renewal |
| JP5639338B2 (ja) | 2005-07-27 | 2014-12-10 | プロチバ バイオセラピューティクス インコーポレイティッド | リポソームの製造システムおよび製造方法 |
| US20120128631A1 (en) * | 2009-05-19 | 2012-05-24 | San Diego State University (SDSU) Foundation, dba San Diego State University (SDSU) Research | Compositions and methods for kinase-mediated cytoprotection and enhanced cellular engraftment and persistence |
-
2008
- 2008-11-14 CA CA2705862A patent/CA2705862C/en active Active
- 2008-11-14 WO PCT/US2008/083693 patent/WO2009065080A1/en not_active Ceased
- 2008-11-14 EP EP08850768.6A patent/EP2209889B1/en active Active
- 2008-11-14 JP JP2010534249A patent/JP2011503207A/ja active Pending
- 2008-11-14 US US12/742,871 patent/US8617534B2/en active Active
-
2013
- 2013-11-18 US US14/082,760 patent/US20140234265A1/en not_active Abandoned
-
2014
- 2014-07-30 JP JP2014154915A patent/JP5795670B2/ja not_active Expired - Fee Related
-
2016
- 2016-03-23 US US15/078,854 patent/US20160324936A1/en not_active Abandoned
-
2018
- 2018-08-16 US US16/104,047 patent/US20190060417A1/en not_active Abandoned
-
2021
- 2021-03-31 US US17/219,749 patent/US20210322522A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004521108A (ja) * | 2001-01-18 | 2004-07-15 | ザ ボード オブ トラスティーズ オブ ザ リーランド スタンフォード ジュニア ユニバーシティ | δＰＫＣの活性化および阻害のためのペプチド |
| JP2005501802A (ja) * | 2001-01-23 | 2005-01-20 | ボストン サイエンティフィック コーポレイション | 虚血心筋を処置するための限局性心筋注入方法 |
| WO2004113367A1 (ja) * | 2003-06-24 | 2004-12-29 | Keio University | アポトーシス抑制活性を有するペプチド |
Non-Patent Citations (2)
| Title |
|---|
| JPN6013032817; Ａｋｓｏｙ Ｉ ｅｔ ａｌ．: 'Ｓｅｌｆ-ｒｅｎｅｗａｌ ｏｆ ｍｕｒｉｎｅ ｅｍｂｒｙｏｎｉｃ ｓｔｅｍ ｃｅｌｌｓ ｉｓ ｓｕｐｐｏｒｔｅｄ ｂｙ ｔｈｅ ｓｅｒｉｎｅ／ｔｈｒｅｏｎｉｎｅ ｋｉｎａｓｅｓ Ｐｉｍ-１ ａｎｄ Ｐ' Ｓｔｅｍ Ｃｅｌｌｓ． Ｖｏｌ．２５ Ｎｏ．１２, 20070823, ｐｐ．２９９６-３００４ * |
| JPN7013002473; Ｍｕｒａｓｋｉ ＪＡ ｅｔ ａｌ．: 'Ｐｉｍ-１ ｒｅｇｕｌａｔｅｓ ｃａｒｄｉｏｍｙｏｃｙｔｅ ｓｕｒｖｉｖａｌ ｄｏｗｎｓｔｒｅａｍ ｏｆ Ａｋｔ' Ｃｉｒｃｕｌａｔｉｏｎ Ｖｏｌ．１１４ Ｎｏ．１８ Ｓｕｐｐｌ．Ｓ, 20061031, ｐｐ．２９４ * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2015007063A (ja) | 2015-01-15 |
| US20190060417A1 (en) | 2019-02-28 |
| US8617534B2 (en) | 2013-12-31 |
| EP2209889A1 (en) | 2010-07-28 |
| EP2209889A4 (en) | 2012-09-05 |
| EP2209889B1 (en) | 2016-07-20 |
| JP5795670B2 (ja) | 2015-10-14 |
| WO2009065080A1 (en) | 2009-05-22 |
| CA2705862A1 (en) | 2009-05-22 |
| US20210322522A1 (en) | 2021-10-21 |
| US20140234265A1 (en) | 2014-08-21 |
| CA2705862C (en) | 2018-03-27 |
| US20100316701A1 (en) | 2010-12-16 |
| US20160324936A1 (en) | 2016-11-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5795670B2 (ja) | 循環系細胞におけるｐｉｍ−１活性を操作するための組成物および方法 | |
| ES2770073T3 (es) | Uso terapéutico de proteínas morfogenéticas óseas | |
| JP2016516423A (ja) | 心筋症を処置するための遺伝子治療ベクター | |
| Lal et al. | Troponin I-Interacting Protein Kinase–A Novel Cardiac-Specific Kinase, Emerging as a Molecular Target for the Treatment of Cardiac Disease– | |
| JP7193874B2 (ja) | 筋肉Ａキナーゼアンカータンパク質（ｍＡＫＡＰ）作用の阻害による心臓病の処置 | |
| CN112472690B (zh) | 一种制备增强CNPase活性的化合物或生物药物的方法用于治疗心脏疾病 | |
| Gu et al. | RhNRG-1β protects the myocardium against irradiation-induced damage via the ErbB2-ERK-SIRT1 signaling pathway | |
| EP3004343A1 (en) | Cycle adenosine monophosphate-incompetent adenylyl cyclase and compositions and methods for treating heart failure and increasing cardiac function | |
| US9550981B2 (en) | Modified tafazzin proteins and methods of making and using the same | |
| CN1882687B (zh) | 心肌细胞的增殖方法 | |
| CN109937045A (zh) | 局部缺血/再灌注损伤 | |
| ES3006614T3 (en) | Relaxin receptor 1 for use in treatment and prevention of heart failure | |
| KR102175170B1 (ko) | HBV enhancer 억제인자 ACK1을 포함하는 B형 간염 치료용 조성물 | |
| US20070213263A1 (en) | Methods And Compositions Using Adiponectin For Treatment Of Cardiac Disorders And For Stimulation Of Angiogenesis | |
| US8496928B2 (en) | Method for preventing and treating cardiovascular diseases with BRCA1 | |
| CN101125198A (zh) | Hsp27在改善缺血后心脏收缩功能方面的应用 | |
| Pan et al. | Myofibroblast-specific inhibition of ASPP1 alleviates myocardial fibrosis by enhancing p53 degradation | |
| EP3689896A1 (en) | Grk2 modulating mirnas | |
| Maharsy | Enhancing Cardiomyocyte Survival in Drug Induced Cardiac Injury | |
| Tsui | The Role of p21-Activated Kinase 1 (Pak1) in the Heart |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7426 Effective date: 20101110 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20101110 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111109 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20111109 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130702 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130926 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131003 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131225 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140401 |