CA2705862C - Compositions and method for manipulating pim-1 activity in circulatory system cells - Google Patents
Compositions and method for manipulating pim-1 activity in circulatory system cells Download PDFInfo
- Publication number
- CA2705862C CA2705862C CA2705862A CA2705862A CA2705862C CA 2705862 C CA2705862 C CA 2705862C CA 2705862 A CA2705862 A CA 2705862A CA 2705862 A CA2705862 A CA 2705862A CA 2705862 C CA2705862 C CA 2705862C
- Authority
- CA
- Canada
- Prior art keywords
- pim
- cardiac
- cell
- injury
- expression
- 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.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 93
- 101001001642 Xenopus laevis Serine/threonine-protein kinase pim-3 Proteins 0.000 title claims description 458
- 238000000034 method Methods 0.000 title abstract description 104
- 230000000694 effects Effects 0.000 title description 75
- 210000000130 stem cell Anatomy 0.000 claims abstract description 141
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 79
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 79
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 78
- 210000002064 heart cell Anatomy 0.000 claims abstract description 74
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 51
- 230000006907 apoptotic process Effects 0.000 claims abstract description 48
- 206010021143 Hypoxia Diseases 0.000 claims abstract description 32
- 230000001939 inductive effect Effects 0.000 claims abstract description 28
- 230000002708 enhancing effect Effects 0.000 claims abstract description 20
- 230000007954 hypoxia Effects 0.000 claims abstract description 13
- 230000001172 regenerating effect Effects 0.000 claims abstract description 12
- 210000004027 cell Anatomy 0.000 claims description 192
- 230000014509 gene expression Effects 0.000 claims description 182
- 230000000747 cardiac effect Effects 0.000 claims description 137
- 210000004413 cardiac myocyte Anatomy 0.000 claims description 93
- 210000001519 tissue Anatomy 0.000 claims description 85
- 210000004165 myocardium Anatomy 0.000 claims description 70
- 210000000056 organ Anatomy 0.000 claims description 55
- 230000006378 damage Effects 0.000 claims description 53
- 210000000107 myocyte Anatomy 0.000 claims description 53
- 241000282414 Homo sapiens Species 0.000 claims description 47
- 230000002018 overexpression Effects 0.000 claims description 44
- 210000005167 vascular cell Anatomy 0.000 claims description 44
- 208000014674 injury Diseases 0.000 claims description 42
- 206010020880 Hypertrophy Diseases 0.000 claims description 41
- 208000010125 myocardial infarction Diseases 0.000 claims description 40
- 208000027418 Wounds and injury Diseases 0.000 claims description 39
- 230000002792 vascular Effects 0.000 claims description 33
- 102000004433 Proto-Oncogene Proteins c-pim-1 Human genes 0.000 claims description 31
- 108010017121 Proto-Oncogene Proteins c-pim-1 Proteins 0.000 claims description 31
- 238000001727 in vivo Methods 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
- 239000003981 vehicle Substances 0.000 claims description 27
- 230000001413 cellular effect Effects 0.000 claims description 26
- 241000700605 Viruses Species 0.000 claims description 24
- 210000005003 heart tissue Anatomy 0.000 claims description 24
- 108091000080 Phosphotransferase Proteins 0.000 claims description 23
- 102000020233 phosphotransferase Human genes 0.000 claims description 23
- 206010019280 Heart failures Diseases 0.000 claims description 22
- 208000013875 Heart injury Diseases 0.000 claims description 21
- 230000004217 heart function Effects 0.000 claims description 19
- 102000040430 polynucleotide Human genes 0.000 claims description 17
- 108091033319 polynucleotide Proteins 0.000 claims description 17
- 239000002157 polynucleotide Substances 0.000 claims description 17
- 206010063837 Reperfusion injury Diseases 0.000 claims description 15
- 230000001969 hypertrophic effect Effects 0.000 claims description 15
- 239000013612 plasmid Substances 0.000 claims description 15
- 208000015181 infectious disease Diseases 0.000 claims description 14
- 239000013603 viral vector Substances 0.000 claims description 14
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 11
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 claims description 11
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 claims description 11
- 230000000735 allogeneic effect Effects 0.000 claims description 10
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 9
- 230000001976 improved effect Effects 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 206010002660 Anoxia Diseases 0.000 claims description 8
- 241000976983 Anoxia Species 0.000 claims description 8
- 208000006029 Cardiomegaly Diseases 0.000 claims description 8
- 230000007953 anoxia Effects 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 208000019622 heart disease Diseases 0.000 claims description 8
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 8
- 230000036044 hypoxaemia Effects 0.000 claims description 8
- 208000012947 ischemia reperfusion injury Diseases 0.000 claims description 8
- 230000000302 ischemic effect Effects 0.000 claims description 8
- 208000020446 Cardiac disease Diseases 0.000 claims description 7
- 208000037906 ischaemic injury Diseases 0.000 claims description 7
- 208000007848 Alcoholism Diseases 0.000 claims description 6
- 206010061218 Inflammation Diseases 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
- 239000013604 expression vector Substances 0.000 claims description 6
- 230000004054 inflammatory process Effects 0.000 claims description 6
- 210000004504 adult stem cell Anatomy 0.000 claims description 5
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 5
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 claims description 4
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 claims description 4
- 210000004507 artificial chromosome Anatomy 0.000 claims description 4
- 210000002308 embryonic cell Anatomy 0.000 claims description 4
- 210000004700 fetal blood Anatomy 0.000 claims description 4
- 238000002513 implantation Methods 0.000 claims description 4
- 230000003169 placental effect Effects 0.000 claims description 4
- 230000000472 traumatic effect Effects 0.000 claims description 4
- 208000035143 Bacterial infection Diseases 0.000 claims description 3
- 208000036142 Viral infection Diseases 0.000 claims description 3
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 3
- 230000001146 hypoxic effect Effects 0.000 claims description 3
- 230000009385 viral infection Effects 0.000 claims description 3
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 abstract description 18
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 abstract description 18
- 230000004663 cell proliferation Effects 0.000 abstract description 10
- 108091008611 Protein Kinase B Proteins 0.000 description 103
- 101000595531 Homo sapiens Serine/threonine-protein kinase pim-1 Proteins 0.000 description 97
- 102100036077 Serine/threonine-protein kinase pim-1 Human genes 0.000 description 91
- 239000013598 vector Substances 0.000 description 90
- 230000001965 increasing effect Effects 0.000 description 72
- 239000013316 polymer of intrinsic microporosity Substances 0.000 description 71
- 241000699670 Mus sp. Species 0.000 description 44
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 42
- 108090000623 proteins and genes Proteins 0.000 description 42
- 206010061216 Infarction Diseases 0.000 description 40
- 238000011282 treatment Methods 0.000 description 39
- 230000004083 survival effect Effects 0.000 description 36
- 241001465754 Metazoa Species 0.000 description 35
- 230000011664 signaling Effects 0.000 description 35
- 230000007574 infarction Effects 0.000 description 34
- 238000003119 immunoblot Methods 0.000 description 32
- 102000004169 proteins and genes Human genes 0.000 description 32
- 230000002107 myocardial effect Effects 0.000 description 30
- 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
- 230000003612 virological effect Effects 0.000 description 25
- 150000001875 compounds Chemical class 0.000 description 24
- 238000009472 formulation Methods 0.000 description 24
- 230000006870 function Effects 0.000 description 24
- 230000003293 cardioprotective effect Effects 0.000 description 23
- 239000002502 liposome Substances 0.000 description 23
- 230000007423 decrease Effects 0.000 description 22
- 239000003814 drug Substances 0.000 description 22
- -1 e.g. Proteins 0.000 description 22
- 238000005259 measurement Methods 0.000 description 22
- 230000000004 hemodynamic effect Effects 0.000 description 21
- 230000003247 decreasing effect Effects 0.000 description 20
- 238000002347 injection Methods 0.000 description 20
- 239000007924 injection Substances 0.000 description 20
- 102400000686 Endothelin-1 Human genes 0.000 description 19
- 101800004490 Endothelin-1 Proteins 0.000 description 19
- 230000001404 mediated effect Effects 0.000 description 18
- 230000035755 proliferation Effects 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 230000009261 transgenic effect Effects 0.000 description 18
- 241000701161 unidentified adenovirus Species 0.000 description 18
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 16
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 16
- 230000006698 induction Effects 0.000 description 16
- 230000036722 left ventricular developed pressure Effects 0.000 description 16
- 230000026731 phosphorylation Effects 0.000 description 16
- 238000006366 phosphorylation reaction Methods 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 15
- 208000028867 ischemia Diseases 0.000 description 15
- 108700019146 Transgenes Proteins 0.000 description 14
- 230000004913 activation Effects 0.000 description 14
- 238000000338 in vitro Methods 0.000 description 14
- 239000006166 lysate Substances 0.000 description 14
- 108090000765 processed proteins & peptides Proteins 0.000 description 14
- 230000001105 regulatory effect Effects 0.000 description 14
- 230000004044 response Effects 0.000 description 14
- 230000007755 survival signaling Effects 0.000 description 14
- 241000699666 Mus <mouse, genus> Species 0.000 description 13
- 108010029485 Protein Isoforms Proteins 0.000 description 13
- 102000001708 Protein Isoforms Human genes 0.000 description 13
- 229960004679 doxorubicin Drugs 0.000 description 13
- 238000002372 labelling Methods 0.000 description 13
- 239000002105 nanoparticle Substances 0.000 description 13
- 210000004940 nucleus Anatomy 0.000 description 13
- 239000002245 particle Substances 0.000 description 13
- 230000001640 apoptogenic effect Effects 0.000 description 12
- 230000001419 dependent effect Effects 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 230000001681 protective effect Effects 0.000 description 12
- 230000001225 therapeutic effect Effects 0.000 description 12
- 108020004705 Codon Proteins 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 11
- 241000725303 Human immunodeficiency virus Species 0.000 description 11
- 230000030833 cell death Effects 0.000 description 11
- 150000002632 lipids Chemical class 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- 238000010361 transduction Methods 0.000 description 11
- 230000026683 transduction Effects 0.000 description 11
- 238000011830 transgenic mouse model Methods 0.000 description 11
- 230000002861 ventricular Effects 0.000 description 11
- 102000004127 Cytokines Human genes 0.000 description 10
- 108090000695 Cytokines 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
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 10
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 10
- 241000699660 Mus musculus Species 0.000 description 10
- 101100297651 Mus musculus Pim2 gene Proteins 0.000 description 10
- 108700020796 Oncogene Proteins 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 230000035508 accumulation Effects 0.000 description 10
- 238000009825 accumulation Methods 0.000 description 10
- 239000013543 active substance Substances 0.000 description 10
- 230000001756 cardiomyopathic effect Effects 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 108020004999 messenger RNA Proteins 0.000 description 10
- 235000002639 sodium chloride Nutrition 0.000 description 10
- 239000005720 sucrose Substances 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 9
- 230000002401 inhibitory effect 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
- 206010016654 Fibrosis Diseases 0.000 description 8
- 230000002424 anti-apoptotic effect Effects 0.000 description 8
- 102000055104 bcl-X Human genes 0.000 description 8
- 108700000711 bcl-X Proteins 0.000 description 8
- 238000004624 confocal microscopy Methods 0.000 description 8
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 8
- 230000004761 fibrosis Effects 0.000 description 8
- 230000012010 growth Effects 0.000 description 8
- 230000002779 inactivation Effects 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
- 230000002265 prevention Effects 0.000 description 8
- 238000007634 remodeling Methods 0.000 description 8
- 230000008439 repair process Effects 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- 238000004904 shortening Methods 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 238000013518 transcription Methods 0.000 description 8
- 230000035897 transcription Effects 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
- 230000032459 dedifferentiation Effects 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 238000001415 gene therapy Methods 0.000 description 7
- 238000011068 loading method Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 230000002062 proliferating effect Effects 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 230000010410 reperfusion Effects 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
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 230000005961 cardioprotection Effects 0.000 description 6
- 230000005779 cell damage Effects 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 230000008828 contractile function Effects 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 230000018109 developmental process 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
- 238000002592 echocardiography Methods 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
- 230000002068 genetic effect Effects 0.000 description 6
- 238000011813 knockout mouse model Methods 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- 102000005681 phospholamban Human genes 0.000 description 6
- 108010059929 phospholamban Proteins 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
- 239000000725 suspension Substances 0.000 description 6
- 239000002562 thickening agent Substances 0.000 description 6
- 238000002054 transplantation Methods 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
- 206010056370 Congestive cardiomyopathy Diseases 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
- 201000010046 Dilated cardiomyopathy Diseases 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
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 5
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 5
- 101100352234 Homo sapiens PIM1 gene Proteins 0.000 description 5
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 5
- 108010009711 Phalloidine Proteins 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
- 230000009471 action Effects 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 230000010261 cell growth 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
- 239000007859 condensation product Substances 0.000 description 5
- 230000001086 cytosolic effect Effects 0.000 description 5
- 230000000994 depressogenic effect Effects 0.000 description 5
- 230000003205 diastolic effect Effects 0.000 description 5
- 230000004069 differentiation Effects 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 5
- 102000053248 human PIM1 Human genes 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000003632 microfilament Anatomy 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
- 229920001184 polypeptide Polymers 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000001177 retroviral effect Effects 0.000 description 5
- 230000019491 signal transduction 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
- 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
- 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
- 229920000084 Gum arabic Polymers 0.000 description 4
- 206010061598 Immunodeficiency Diseases 0.000 description 4
- 208000029462 Immunodeficiency disease Diseases 0.000 description 4
- 241000713666 Lentivirus Species 0.000 description 4
- 108091061960 Naked DNA Proteins 0.000 description 4
- 206010028851 Necrosis Diseases 0.000 description 4
- 229940122907 Phosphatase inhibitor Drugs 0.000 description 4
- 241000288906 Primates Species 0.000 description 4
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 4
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 235000010489 acacia gum Nutrition 0.000 description 4
- 230000004075 alteration Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 102000007348 bcl-Associated Death Protein Human genes 0.000 description 4
- 108010007734 bcl-Associated Death Protein Proteins 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 210000000748 cardiovascular system Anatomy 0.000 description 4
- 238000000942 confocal micrograph Methods 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 230000035487 diastolic blood pressure Effects 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 230000007813 immunodeficiency Effects 0.000 description 4
- 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 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 230000000670 limiting effect Effects 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
- 238000001000 micrograph Methods 0.000 description 4
- 238000002156 mixing Methods 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
- 230000001575 pathological effect Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000004321 preservation Methods 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 210000003705 ribosome Anatomy 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 239000003381 stabilizer 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
- 230000008685 targeting Effects 0.000 description 4
- 230000001052 transient effect Effects 0.000 description 4
- 230000003827 upregulation Effects 0.000 description 4
- 210000005166 vasculature Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- 244000215068 Acacia senegal Species 0.000 description 3
- 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 3
- 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 3
- 241000416162 Astragalus gummifer Species 0.000 description 3
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 3
- 208000005623 Carcinogenesis Diseases 0.000 description 3
- 108090000397 Caspase 3 Proteins 0.000 description 3
- 102000003952 Caspase 3 Human genes 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- 108010063738 Interleukins 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
- 241001529936 Murinae Species 0.000 description 3
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 3
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 3
- 241000713883 Myeloproliferative sarcoma virus Species 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 102000043276 Oncogene Human genes 0.000 description 3
- 239000002202 Polyethylene glycol Substances 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
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 3
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 3
- 229920001615 Tragacanth Polymers 0.000 description 3
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 3
- 108020004566 Transfer RNA Proteins 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000009692 acute damage Effects 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 230000032683 aging Effects 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
- 239000007900 aqueous suspension Substances 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 230000002759 chromosomal effect Effects 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 210000004351 coronary vessel Anatomy 0.000 description 3
- 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 3
- 230000007123 defense Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 108700004025 env Genes Proteins 0.000 description 3
- 101150030339 env gene Proteins 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
- 235000003599 food sweetener 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
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 230000006872 improvement Effects 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
- 230000007246 mechanism Effects 0.000 description 3
- 239000004005 microsphere Substances 0.000 description 3
- 230000002438 mitochondrial effect Effects 0.000 description 3
- 230000011278 mitosis Effects 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000030648 nucleus localization Effects 0.000 description 3
- 231100000590 oncogenic Toxicity 0.000 description 3
- 230000002246 oncogenic effect Effects 0.000 description 3
- 230000004792 oxidative damage Effects 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 230000003076 paracrine Effects 0.000 description 3
- 229960001802 phenylephrine Drugs 0.000 description 3
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 230000000861 pro-apoptotic effect Effects 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 230000004224 protection Effects 0.000 description 3
- 108010083755 proto-oncogene proteins pim Proteins 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 239000012723 sample buffer Substances 0.000 description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- 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 description 3
- 230000035899 viability Effects 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
- 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 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
- 208000030507 AIDS Diseases 0.000 description 2
- 235000006491 Acacia senegal Nutrition 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- 230000007730 Akt signaling Effects 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
- 241000713704 Bovine immunodeficiency virus Species 0.000 description 2
- 238000009010 Bradford assay Methods 0.000 description 2
- 102000004612 Calcium-Transporting ATPases Human genes 0.000 description 2
- 108010017954 Calcium-Transporting ATPases Proteins 0.000 description 2
- 241000713756 Caprine arthritis encephalitis virus Species 0.000 description 2
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 description 2
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 description 2
- 108700010070 Codon Usage Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 2
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- 241000196324 Embryophyta Species 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
- 102100031690 Erythroid transcription factor Human genes 0.000 description 2
- 101710100588 Erythroid transcription factor Proteins 0.000 description 2
- 241000713800 Feline immunodeficiency virus Species 0.000 description 2
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 2
- 102100038104 Glycogen synthase kinase-3 beta Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin 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
- 108010085220 Multiprotein Complexes Proteins 0.000 description 2
- 102000007474 Multiprotein Complexes Human genes 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- 102000042867 PIM family Human genes 0.000 description 2
- 108091082273 PIM family Proteins 0.000 description 2
- 101800004021 PP2-A Proteins 0.000 description 2
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 2
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 2
- 102000003946 Prolactin Human genes 0.000 description 2
- 108010057464 Prolactin Proteins 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 102000001253 Protein Kinase Human genes 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
- 101710109123 Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 Proteins 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 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
- 238000002679 ablation Methods 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000000205 acacia gum Substances 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
- 239000012190 activator Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000003044 adaptive effect 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
- 230000003321 amplification Effects 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000002421 anti-septic effect Effects 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000005756 apoptotic signaling Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000035578 autophosphorylation Effects 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
- 239000000872 buffer Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000002771 cell marker Substances 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 230000006364 cellular survival Effects 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 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
- 230000001684 chronic effect Effects 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000003292 diminished effect Effects 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 108010027225 gag-pol Fusion Proteins Proteins 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 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 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000000021 kinase assay Methods 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
- 210000005240 left ventricle Anatomy 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
- 239000012931 lyophilized formulation Substances 0.000 description 2
- 230000034701 macropinocytosis Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 210000000723 mammalian artificial chromosome Anatomy 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
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000009456 molecular mechanism Effects 0.000 description 2
- 210000002894 multi-fate stem cell Anatomy 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 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
- 230000001566 pro-viral effect Effects 0.000 description 2
- 229940097325 prolactin Drugs 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
- 108060006633 protein kinase Proteins 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 210000001908 sarcoplasmic reticulum Anatomy 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000009758 senescence Effects 0.000 description 2
- 210000002966 serum Anatomy 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
- 239000012439 solid excipient Substances 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
- 238000007619 statistical method Methods 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 239000000126 substance Substances 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
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000375 suspending agent Substances 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
- 229930003799 tocopherol Natural products 0.000 description 2
- 229960001295 tocopherol Drugs 0.000 description 2
- 235000010384 tocopherol Nutrition 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 230000002463 transducing effect Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 230000014616 translation Effects 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
- 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 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 compound 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
- SVDOODSCHVSYEK-IFLJXUKPSA-N (4s,4ar,5s,5ar,6s,12ar)-4-(dimethylamino)-1,5,6,10,11,12a-hexahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide;hydron;chloride Chemical compound Cl.C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O SVDOODSCHVSYEK-IFLJXUKPSA-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
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- 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 1
- DOSMHBDKKKMIEF-UHFFFAOYSA-N 2-[3-(diethylamino)-6-diethylazaniumylidenexanthen-9-yl]-5-[3-[3-[4-(1-methylindol-3-yl)-2,5-dioxopyrrol-3-yl]indol-1-yl]propylsulfamoyl]benzenesulfonate Chemical compound C1=CC(=[N+](CC)CC)C=C2OC3=CC(N(CC)CC)=CC=C3C(C=3C(=CC(=CC=3)S(=O)(=O)NCCCN3C4=CC=CC=C4C(C=4C(NC(=O)C=4C=4C5=CC=CC=C5N(C)C=4)=O)=C3)S([O-])(=O)=O)=C21 DOSMHBDKKKMIEF-UHFFFAOYSA-N 0.000 description 1
- GJJVAFUKOBZPCB-UHFFFAOYSA-N 2-methyl-2-(4,8,12-trimethyltrideca-3,7,11-trienyl)-3,4-dihydrochromen-6-ol Chemical compound OC1=CC=C2OC(CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1 GJJVAFUKOBZPCB-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
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 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 1
- 240000008025 Alternanthera ficoidea Species 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
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010007558 Cardiac failure chronic Diseases 0.000 description 1
- 206010054212 Cardiac infection Diseases 0.000 description 1
- 208000031229 Cardiomyopathies 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
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 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
- 102100033270 Cyclin-dependent kinase inhibitor 1 Human genes 0.000 description 1
- 101710132484 Cytokine-inducible SH2-containing protein Proteins 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
- 101000944380 Homo sapiens Cyclin-dependent kinase inhibitor 1 Proteins 0.000 description 1
- 101000798007 Homo sapiens RAC-gamma serine/threonine-protein kinase Proteins 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
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 229920000161 Locust bean gum Polymers 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 208000029549 Muscle injury Diseases 0.000 description 1
- 102100026925 Myosin regulatory light chain 2, ventricular/cardiac muscle isoform Human genes 0.000 description 1
- 101710105127 Myosin regulatory light chain 2, ventricular/cardiac muscle isoform Proteins 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 108091005461 Nucleic proteins Proteins 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
- 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
- 239000012828 PI3K inhibitor Substances 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
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 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
- 108010058956 Protein Phosphatase 2 Proteins 0.000 description 1
- 102000006478 Protein Phosphatase 2 Human genes 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 108700020978 Proto-Oncogene 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
- 102100032314 RAC-gamma serine/threonine-protein kinase 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
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 108010029477 STAT5 Transcription Factor Proteins 0.000 description 1
- 102000001712 STAT5 Transcription Factor Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 102100027732 Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 Human genes 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000713311 Simian immunodeficiency virus Species 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
- 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
- 102000004987 Troponin T Human genes 0.000 description 1
- 108090001108 Troponin T 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
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 108010087302 Viral Structural Proteins Proteins 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 101100297656 Xenopus laevis pim3 gene 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
- 108010023249 Zyxin Proteins 0.000 description 1
- 102100023895 Zyxin Human genes 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
- 208000037892 acute myocardial injury Diseases 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
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000009949 anti-apoptotic pathway Effects 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
- 230000003064 anti-oxidating effect Effects 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
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 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
- 239000001168 astaxanthin Substances 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
- 229940022405 astaxanthin Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 238000000376 autoradiography Methods 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
- 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
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 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
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 230000009787 cardiac fibrosis Effects 0.000 description 1
- 210000001196 cardiac muscle myoblast Anatomy 0.000 description 1
- 229940045200 cardioprotective agent Drugs 0.000 description 1
- 239000012659 cardioprotective agent Substances 0.000 description 1
- 239000000969 carrier Substances 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
- 230000006727 cell loss 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
- 230000030570 cellular localization Effects 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- 150000001783 ceramides Chemical class 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 238000011281 clinical therapy Methods 0.000 description 1
- 238000011260 co-administration Methods 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
- 230000001010 compromised effect Effects 0.000 description 1
- 230000002153 concerted effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010226 confocal imaging Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000013270 controlled release Methods 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
- 230000002596 correlated effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000011243 crosslinked material Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 229940126513 cyclase activator Drugs 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229940124447 delivery agent Drugs 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003090 exacerbative effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 235000019197 fats Nutrition 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
- 230000037406 food intake Effects 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 238000011773 genetically engineered mouse model Methods 0.000 description 1
- 238000012268 genome sequencing Methods 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000005986 heart dysfunction Effects 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 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 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
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000010820 immunofluorescence microscopy Methods 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000003116 impacting effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000012606 in vitro cell culture Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 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
- 238000013383 initial experiment Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000010354 integration 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
- 229940047122 interleukins Drugs 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
- 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
- 230000000366 juvenile effect Effects 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000004185 liver Anatomy 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
- 239000007937 lozenge Substances 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 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
- 239000002609 medium Substances 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
- 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
- 210000003205 muscle Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 210000003098 myoblast Anatomy 0.000 description 1
- 230000010016 myocardial function Effects 0.000 description 1
- 208000037891 myocardial injury Diseases 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
- 229920005615 natural polymer Polymers 0.000 description 1
- 230000007935 neutral effect Effects 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
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
- 239000012053 oil suspension 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
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 239000003002 pH adjusting agent 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
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000011148 porous material Substances 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
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000009219 proapoptotic pathway Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011321 prophylaxis Methods 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
- 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
- 238000009877 rendering Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 108010038196 saccharide-binding proteins Proteins 0.000 description 1
- 235000019204 saccharin Nutrition 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
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 102000009023 sarcolipin Human genes 0.000 description 1
- 108010088766 sarcolipin Proteins 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 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
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 210000000952 spleen Anatomy 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
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 238000009580 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
- 230000035882 stress Effects 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 235000012222 talc Nutrition 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
- 229930003802 tocotrienol Natural products 0.000 description 1
- 239000011731 tocotrienol Substances 0.000 description 1
- 235000019148 tocotrienols Nutrition 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
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000012301 transgenic model Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000005945 translocation Effects 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
- 230000006444 vascular growth Effects 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000005570 vertical transmission Effects 0.000 description 1
- 210000000605 viral structure Anatomy 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 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
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)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Developmental Biology & Embryology (AREA)
- Cardiology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hematology (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Hospice & Palliative Care (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US98875307P | 2007-11-16 | 2007-11-16 | |
| US60/988,753 | 2007-11-16 | ||
| US9169808P | 2008-08-25 | 2008-08-25 | |
| US61/091,698 | 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 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2705862A1 CA2705862A1 (en) | 2009-05-22 |
| CA2705862C true CA2705862C (en) | 2018-03-27 |
Family
ID=40639186
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2705862A Active CA2705862C (en) | 2007-11-16 | 2008-11-14 | Compositions and method for manipulating pim-1 activity in circulatory system cells |
Country Status (5)
| Country | Link |
|---|---|
| US (5) | US8617534B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2209889B1 (cg-RX-API-DMAC7.html) |
| JP (2) | JP2011503207A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2705862C (cg-RX-API-DMAC7.html) |
| WO (1) | WO2009065080A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUE036640T2 (hu) * | 2012-02-14 | 2018-07-30 | Univ California | Parakrin gének szisztémás bejuttatása és szabályozott expressziója szív és érrendszeri betegségekre és egyéb állapotokra |
| CA2897200C (en) | 2013-01-14 | 2021-07-06 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors |
| AR094664A1 (es) | 2013-01-15 | 2015-08-19 | Incyte Corp | Compuestos de tiazolcarboxamidas y piridinacarboxamida utiles como inhibidores de quinasa pim |
| 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 |
| US9822124B2 (en) | 2014-07-14 | 2017-11-21 | Incyte Corporation | Bicyclic heteroaromatic carboxamide compounds useful as Pim kinase inhibitors |
| US9540347B2 (en) | 2015-05-29 | 2017-01-10 | 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 |
| TW201718546A (zh) | 2015-10-02 | 2017-06-01 | 英塞特公司 | 適用作pim激酶抑制劑之雜環化合物 |
| EP3638331A4 (en) | 2017-06-16 | 2021-03-17 | Avery Therapeutics, Inc. | THREE-DIMENSIONAL TISSUE COMPOSITIONS AND METHODS OF APPLICATION |
| AR113922A1 (es) | 2017-12-08 | 2020-07-01 | Incyte Corp | Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas |
| 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 |
| US20210386827A1 (en) * | 2018-10-15 | 2021-12-16 | Avery Therapeutics, Inc. | Cell-free compositions and methods for restoration or enhancement of tissue function |
| IL295529A (en) | 2020-02-13 | 2022-10-01 | Tenaya Therapeutics Inc | Gene therapy vectors for treating heart disease |
| CN116018258A (zh) * | 2020-09-04 | 2023-04-25 | 迪睿合株式会社 | 导电性层叠体及使用其的光学装置、导电性层叠体的制造方法 |
Family Cites Families (35)
| 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 |
| JP2002514908A (ja) * | 1996-09-05 | 2002-05-21 | 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 | うっ血性心不全のための遺伝子治療 |
| CA2267636A1 (en) | 1996-10-17 | 1998-04-30 | Alan John Kingsman | Retroviral vectors |
| US7198784B2 (en) | 1996-10-17 | 2007-04-03 | Oxford Biomedica (Uk) Limited | Retroviral vectors |
| 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 |
| CA2288328A1 (en) | 1997-05-13 | 1998-11-19 | University Of North Carolina At Chapel Hill | Lentivirus-based gene transfer vectors |
| AU8285998A (en) | 1997-07-02 | 1999-01-25 | Sdg, Inc. | Targeted liposomal constructs for diagnostic and therapeutic uses |
| ES2245042T3 (es) | 1997-09-24 | 2005-12-16 | The Regents Of The University Of California | Vectores de lentivirus de no primates y sistemas de empaquetamiento. |
| DK1895010T3 (da) | 1997-12-22 | 2011-11-21 | Oxford Biomedica Ltd | Vektorer baseret på virus for infektiøs hesteanæmi (eiav) |
| 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 |
| EP1351980B1 (en) * | 2001-01-18 | 2014-12-31 | The Board Of Trustees Of The Leland Stanford Junior University | Peptides for activation and inhibition of delta pkc |
| CA2433936A1 (en) * | 2001-01-23 | 2002-08-22 | Boston Scientific Corporation | Localized myocardial injection method for treating ischemic myocardium |
| 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 |
| CA2915676C (en) | 2001-10-02 | 2017-06-06 | Institut Clayton De La Recherche | Restricted expression lentiviral vectors |
| US20040258669A1 (en) * | 2002-11-05 | 2004-12-23 | Dzau Victor J. | Mesenchymal stem cells and methods of use thereof |
| EP1624073A4 (en) * | 2003-04-03 | 2006-05-17 | Oncorex Inc | DRUG |
| AU2004249601A1 (en) * | 2003-06-24 | 2004-12-29 | Keio University | Peptide having apoptosis-inhibiting activity |
| 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) |
| EP1698329A4 (en) | 2003-12-24 | 2009-10-28 | Ltt Bio Pharma Co Ltd | PHARMACEUTICAL NANOTEILS, METHOD FOR THE PRODUCTION THEREOF AND PARENTERALLY APPLIED PRODUCT FROM NANOTEILES |
| EP1722762A2 (en) | 2004-03-02 | 2006-11-22 | Massachusetts Institute of Technology | Nanocell drug delivery system |
| US20070082042A1 (en) | 2004-08-06 | 2007-04-12 | Deok-Hoon Park | Multiple-layered liposome and preparation method thereof |
| JP5202953B2 (ja) * | 2004-11-08 | 2013-06-05 | ザ ジョンズ ホプキンス ユニバーシティー | 心臓幹細胞 |
| WO2006125321A1 (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 |
| CN101267805A (zh) | 2005-07-27 | 2008-09-17 | 普洛体维生物治疗公司 | 制造脂质体的系统和方法 |
| WO2010135401A2 (en) * | 2009-05-19 | 2010-11-25 | San Diego State University Foundation | Kinase-mediated cytoprotection and enhanced cellular engraftment and persistence |
-
2008
- 2008-11-14 EP EP08850768.6A patent/EP2209889B1/en active Active
- 2008-11-14 JP JP2010534249A patent/JP2011503207A/ja active Pending
- 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 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
Also Published As
| Publication number | Publication date |
|---|---|
| JP5795670B2 (ja) | 2015-10-14 |
| JP2011503207A (ja) | 2011-01-27 |
| US20100316701A1 (en) | 2010-12-16 |
| CA2705862A1 (en) | 2009-05-22 |
| US8617534B2 (en) | 2013-12-31 |
| US20210322522A1 (en) | 2021-10-21 |
| EP2209889A1 (en) | 2010-07-28 |
| US20190060417A1 (en) | 2019-02-28 |
| US20160324936A1 (en) | 2016-11-10 |
| EP2209889A4 (en) | 2012-09-05 |
| WO2009065080A1 (en) | 2009-05-22 |
| JP2015007063A (ja) | 2015-01-15 |
| EP2209889B1 (en) | 2016-07-20 |
| US20140234265A1 (en) | 2014-08-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20210322522A1 (en) | Compositions and method for manipulating pim-1 activity in circulatory system cells | |
| Tang et al. | Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector | |
| Shiojima et al. | Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure | |
| Du et al. | Hypoxia-inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF) pathway participates in angiogenesis of myocardial infarction in muscone-treated mice: preliminary study | |
| Korpela et al. | Gene therapy for ischaemic heart disease and heart failure | |
| Yang et al. | Physiological functions of protein kinase B/Akt | |
| Song et al. | Down-regulation of microRNA-320 suppresses cardiomyocyte apoptosis and protects against myocardial ischemia and reperfusion injury by targeting IGF-1 | |
| WO2016135723A1 (en) | Mammalian cells enriched with functional mitochondria | |
| Choi et al. | IL-10-secreting human MSCs generated by TALEN gene editing ameliorate liver fibrosis through enhanced anti-fibrotic activity | |
| Ott et al. | Advances in the treatment of chronic granulomatous disease by gene therapy | |
| KR101220516B1 (ko) | 항－ｍｄｍ２를 발현하는 인간 성체줄기세포 및 그의 용도 | |
| Li et al. | Integrin β1 increases stem cell survival and cardiac function after myocardial infarction | |
| Zeng et al. | Paracrine action of HO‐1‐modified mesenchymal stem cells mediates cardiac protection and functional improvement | |
| Huang et al. | Cardiac-specific Traf2 overexpression enhances cardiac hypertrophy through activating AKT/GSK3β signaling | |
| Zeng et al. | ILK regulates MSCs survival and angiogenesis partially through AKT and mTOR signaling pathways | |
| Chen et al. | Mesenchymal stem cells with eNOS over-expression enhance cardiac repair in rats with myocardial infarction | |
| KR20230010617A (ko) | 산화스트레스 저항성을 갖는 중간엽줄기세포, 이의 제조방법 및 용도 | |
| Lyon et al. | The potential of cardiac stem cell therapy for heart failure | |
| CN111705061B (zh) | 和心脏疾病相关的piRNA-P1与piRNA-P1反义核苷酸、应用和药物 | |
| Liu et al. | Dual specific phosphatase 7 exacerbates dilated cardiomyopathy, heart failure, and cardiac death by inactivating the ERK1/2 signaling pathway | |
| de Muinck | Gene and cell therapy for heart failure | |
| US8496928B2 (en) | Method for preventing and treating cardiovascular diseases with BRCA1 | |
| WO2015153357A1 (en) | Compositions and methods for improving cardiac function | |
| EP1682172A2 (en) | Methods and compositions using adiponectin for treatment of cardiac disorders and for stimulation of angiogenesis | |
| CA2977341C (en) | Mammalian cells enriched with functional mitochondria |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20131112 |