JP6622822B2 - 希ガス組成物を用いた治療的な免疫調節 - Google Patents
希ガス組成物を用いた治療的な免疫調節 Download PDFInfo
- Publication number
- JP6622822B2 JP6622822B2 JP2017567439A JP2017567439A JP6622822B2 JP 6622822 B2 JP6622822 B2 JP 6622822B2 JP 2017567439 A JP2017567439 A JP 2017567439A JP 2017567439 A JP2017567439 A JP 2017567439A JP 6622822 B2 JP6622822 B2 JP 6622822B2
- Authority
- JP
- Japan
- Prior art keywords
- xenon
- oxygen
- composition
- autism
- volume
- 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.)
- Expired - Fee Related
Links
- 239000000203 mixture Substances 0.000 title claims description 77
- 229910052756 noble gas Inorganic materials 0.000 title claims description 47
- 230000001225 therapeutic effect Effects 0.000 title description 9
- 230000008102 immune modulation Effects 0.000 title 1
- 229910052760 oxygen Inorganic materials 0.000 claims description 153
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 151
- 239000001301 oxygen Substances 0.000 claims description 151
- 229910052724 xenon Inorganic materials 0.000 claims description 132
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 claims description 132
- 208000029560 autism spectrum disease Diseases 0.000 claims description 84
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 76
- 208000020706 Autistic disease Diseases 0.000 claims description 59
- 206010003805 Autism Diseases 0.000 claims description 58
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims description 42
- 230000002757 inflammatory effect Effects 0.000 claims description 37
- 239000007789 gas Substances 0.000 claims description 33
- 102000004127 Cytokines Human genes 0.000 claims description 32
- 108090000695 Cytokines Proteins 0.000 claims description 32
- 229910052786 argon Inorganic materials 0.000 claims description 25
- 230000001965 increasing effect Effects 0.000 claims description 21
- 238000004519 manufacturing process Methods 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 21
- 238000000338 in vitro Methods 0.000 claims description 11
- 102000013462 Interleukin-12 Human genes 0.000 claims description 10
- 108010065805 Interleukin-12 Proteins 0.000 claims description 10
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 10
- 230000008718 systemic inflammatory response Effects 0.000 claims description 10
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 9
- 208000012902 Nervous system disease Diseases 0.000 claims description 8
- 210000004556 brain Anatomy 0.000 claims description 8
- 210000003169 central nervous system Anatomy 0.000 claims description 7
- 230000016396 cytokine production Effects 0.000 claims description 7
- 208000036640 Asperger disease Diseases 0.000 claims description 6
- 201000006062 Asperger syndrome Diseases 0.000 claims description 6
- 229910052734 helium Inorganic materials 0.000 claims description 6
- 210000002865 immune cell Anatomy 0.000 claims description 6
- 229910052743 krypton Inorganic materials 0.000 claims description 6
- 208000025966 Neurological disease Diseases 0.000 claims description 5
- 208000006289 Rett Syndrome Diseases 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000008246 gaseous mixture Substances 0.000 claims description 5
- 229910052754 neon Inorganic materials 0.000 claims description 5
- 208000012202 Pervasive developmental disease Diseases 0.000 claims description 4
- 230000003444 anaesthetic effect Effects 0.000 claims description 4
- 239000001307 helium Substances 0.000 claims description 4
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 4
- DNNSSWSSYDEUBZ-UHFFFAOYSA-N krypton atom Chemical compound [Kr] DNNSSWSSYDEUBZ-UHFFFAOYSA-N 0.000 claims description 4
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 208000024825 childhood disintegrative disease Diseases 0.000 claims description 2
- 230000028709 inflammatory response Effects 0.000 claims description 2
- 230000002297 mitogenic effect Effects 0.000 claims description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 claims description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims 3
- -1 IL13RA9 Proteins 0.000 description 22
- 238000011282 treatment Methods 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 208000028173 post-traumatic stress disease Diseases 0.000 description 18
- 210000002381 plasma Anatomy 0.000 description 16
- 102000013691 Interleukin-17 Human genes 0.000 description 15
- 108050003558 Interleukin-17 Proteins 0.000 description 15
- 206010021143 Hypoxia Diseases 0.000 description 14
- 239000000902 placebo Substances 0.000 description 14
- 229940068196 placebo Drugs 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 210000001744 T-lymphocyte Anatomy 0.000 description 12
- 102100040247 Tumor necrosis factor Human genes 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 11
- 102100036849 C-C motif chemokine 24 Human genes 0.000 description 10
- 102100025279 C-X-C motif chemokine 11 Human genes 0.000 description 10
- 108090000176 Interleukin-13 Proteins 0.000 description 10
- 102000003816 Interleukin-13 Human genes 0.000 description 10
- 102000004889 Interleukin-6 Human genes 0.000 description 10
- 108090001005 Interleukin-6 Proteins 0.000 description 10
- 229940100601 interleukin-6 Drugs 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- 206010061218 Inflammation Diseases 0.000 description 9
- 102000004890 Interleukin-8 Human genes 0.000 description 9
- 108090001007 Interleukin-8 Proteins 0.000 description 9
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 230000004054 inflammatory process Effects 0.000 description 9
- 230000000638 stimulation Effects 0.000 description 9
- 230000009885 systemic effect Effects 0.000 description 9
- 102100036850 C-C motif chemokine 23 Human genes 0.000 description 8
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 8
- 102100023688 Eotaxin Human genes 0.000 description 8
- 101000713081 Homo sapiens C-C motif chemokine 23 Proteins 0.000 description 8
- 102000000589 Interleukin-1 Human genes 0.000 description 8
- 108010002352 Interleukin-1 Proteins 0.000 description 8
- 102000016267 Leptin Human genes 0.000 description 8
- 108010092277 Leptin Proteins 0.000 description 8
- 239000000427 antigen Substances 0.000 description 8
- 108091007433 antigens Proteins 0.000 description 8
- 102000036639 antigens Human genes 0.000 description 8
- 230000001363 autoimmune Effects 0.000 description 8
- 230000006399 behavior Effects 0.000 description 8
- 238000004891 communication Methods 0.000 description 8
- 230000007954 hypoxia Effects 0.000 description 8
- 229940039781 leptin Drugs 0.000 description 8
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 206010000117 Abnormal behaviour Diseases 0.000 description 7
- 102100023702 C-C motif chemokine 13 Human genes 0.000 description 7
- 102100023700 C-C motif chemokine 16 Human genes 0.000 description 7
- 102100023701 C-C motif chemokine 18 Human genes 0.000 description 7
- 102100021933 C-C motif chemokine 25 Human genes 0.000 description 7
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 7
- 102100036150 C-X-C motif chemokine 5 Human genes 0.000 description 7
- 102100036153 C-X-C motif chemokine 6 Human genes 0.000 description 7
- 101000978375 Homo sapiens C-C motif chemokine 16 Proteins 0.000 description 7
- 101000978371 Homo sapiens C-C motif chemokine 18 Proteins 0.000 description 7
- 101000897486 Homo sapiens C-C motif chemokine 25 Proteins 0.000 description 7
- 101000947186 Homo sapiens C-X-C motif chemokine 5 Proteins 0.000 description 7
- 108010074328 Interferon-gamma Proteins 0.000 description 7
- 108010067003 Interleukin-33 Proteins 0.000 description 7
- 102000017761 Interleukin-33 Human genes 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000003247 decreasing effect Effects 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 230000006872 improvement Effects 0.000 description 7
- 150000002835 noble gases Chemical class 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 230000001629 suppression Effects 0.000 description 7
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 6
- 101100339431 Arabidopsis thaliana HMGB2 gene Proteins 0.000 description 6
- 102100023703 C-C motif chemokine 15 Human genes 0.000 description 6
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 6
- 102100036848 C-C motif chemokine 20 Human genes 0.000 description 6
- 108700010013 HMGB1 Proteins 0.000 description 6
- 101150021904 HMGB1 gene Proteins 0.000 description 6
- 102100037907 High mobility group protein B1 Human genes 0.000 description 6
- 101000978379 Homo sapiens C-C motif chemokine 13 Proteins 0.000 description 6
- 101000978376 Homo sapiens C-C motif chemokine 15 Proteins 0.000 description 6
- 101000713099 Homo sapiens C-C motif chemokine 20 Proteins 0.000 description 6
- 101000713078 Homo sapiens C-C motif chemokine 24 Proteins 0.000 description 6
- 101000858060 Homo sapiens C-X-C motif chemokine 11 Proteins 0.000 description 6
- 101000959794 Homo sapiens Interferon alpha-2 Proteins 0.000 description 6
- 101001055219 Homo sapiens Interleukin-9 receptor Proteins 0.000 description 6
- 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 description 6
- 108091058560 IL8 Proteins 0.000 description 6
- 102100040018 Interferon alpha-2 Human genes 0.000 description 6
- 108010002335 Interleukin-9 Proteins 0.000 description 6
- 102000000585 Interleukin-9 Human genes 0.000 description 6
- 102100026244 Interleukin-9 receptor Human genes 0.000 description 6
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 208000013403 hyperactivity Diseases 0.000 description 6
- 230000001146 hypoxic effect Effects 0.000 description 6
- 230000019734 interleukin-12 production Effects 0.000 description 6
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 6
- 210000001616 monocyte Anatomy 0.000 description 6
- 229960002296 paroxetine Drugs 0.000 description 6
- 230000006433 tumor necrosis factor production Effects 0.000 description 6
- 206010001497 Agitation Diseases 0.000 description 5
- 108010055166 Chemokine CCL5 Proteins 0.000 description 5
- 206010010904 Convulsion Diseases 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
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 5
- 102000008070 Interferon-gamma Human genes 0.000 description 5
- 102000003810 Interleukin-18 Human genes 0.000 description 5
- 108090000171 Interleukin-18 Proteins 0.000 description 5
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 5
- 208000006011 Stroke Diseases 0.000 description 5
- 102000002689 Toll-like receptor Human genes 0.000 description 5
- 108020000411 Toll-like receptor Proteins 0.000 description 5
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 5
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 5
- 230000001464 adherent effect Effects 0.000 description 5
- 230000006735 deficit Effects 0.000 description 5
- 210000004443 dendritic cell Anatomy 0.000 description 5
- 230000004064 dysfunction Effects 0.000 description 5
- 210000000987 immune system Anatomy 0.000 description 5
- 229960003130 interferon gamma Drugs 0.000 description 5
- 210000002540 macrophage Anatomy 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 230000036470 plasma concentration Effects 0.000 description 5
- 230000000770 proinflammatory effect Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 102100031786 Adiponectin Human genes 0.000 description 4
- 108010076365 Adiponectin Proteins 0.000 description 4
- 102100036841 C-C motif chemokine 1 Human genes 0.000 description 4
- 102100023698 C-C motif chemokine 17 Human genes 0.000 description 4
- 102100036846 C-C motif chemokine 21 Human genes 0.000 description 4
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 4
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 4
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 4
- 101710098272 C-X-C motif chemokine 11 Proteins 0.000 description 4
- 102100025277 C-X-C motif chemokine 13 Human genes 0.000 description 4
- 102100025250 C-X-C motif chemokine 14 Human genes 0.000 description 4
- 101710085504 C-X-C motif chemokine 6 Proteins 0.000 description 4
- 102100036170 C-X-C motif chemokine 9 Human genes 0.000 description 4
- 102100034798 CCAAT/enhancer-binding protein beta Human genes 0.000 description 4
- 108010083647 Chemokine CCL24 Proteins 0.000 description 4
- 102100031051 Cysteine and glycine-rich protein 1 Human genes 0.000 description 4
- 208000012239 Developmental disease Diseases 0.000 description 4
- 101710139422 Eotaxin Proteins 0.000 description 4
- 101710115997 Gamma-tubulin complex component 2 Proteins 0.000 description 4
- 108010061711 Gliadin Proteins 0.000 description 4
- 101000713104 Homo sapiens C-C motif chemokine 1 Proteins 0.000 description 4
- 101000978362 Homo sapiens C-C motif chemokine 17 Proteins 0.000 description 4
- 101000858064 Homo sapiens C-X-C motif chemokine 13 Proteins 0.000 description 4
- 101000858068 Homo sapiens C-X-C motif chemokine 14 Proteins 0.000 description 4
- 101000960936 Homo sapiens Interleukin-5 receptor subunit alpha Proteins 0.000 description 4
- 101000668165 Homo sapiens RNA-binding motif, single-stranded-interacting protein 1 Proteins 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102000000588 Interleukin-2 Human genes 0.000 description 4
- 102100030703 Interleukin-22 Human genes 0.000 description 4
- 102100033502 Interleukin-37 Human genes 0.000 description 4
- 108010002616 Interleukin-5 Proteins 0.000 description 4
- 102100039897 Interleukin-5 Human genes 0.000 description 4
- 102100039881 Interleukin-5 receptor subunit alpha Human genes 0.000 description 4
- 102000034655 MIF Human genes 0.000 description 4
- 108060004872 MIF Proteins 0.000 description 4
- 102100040557 Osteopontin Human genes 0.000 description 4
- 108010047620 Phytohemagglutinins Proteins 0.000 description 4
- 108700012411 TNFSF10 Proteins 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 210000001691 amnion Anatomy 0.000 description 4
- 108091006374 cAMP receptor proteins Proteins 0.000 description 4
- 230000002596 correlated effect Effects 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- AEUKDPKXTPNBNY-XEYRWQBLSA-N mcp 2 Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C1=CC=CC=C1 AEUKDPKXTPNBNY-XEYRWQBLSA-N 0.000 description 4
- 230000015654 memory Effects 0.000 description 4
- 230000001885 phytohemagglutinin Effects 0.000 description 4
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 4
- 229960001534 risperidone Drugs 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 230000008733 trauma Effects 0.000 description 4
- 210000002700 urine Anatomy 0.000 description 4
- 102100020979 ATP-binding cassette sub-family F member 1 Human genes 0.000 description 3
- 102100022416 Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 Human genes 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 3
- 102100022718 Atypical chemokine receptor 2 Human genes 0.000 description 3
- 102100021631 B-cell lymphoma 6 protein Human genes 0.000 description 3
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 3
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 3
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 3
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 3
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 3
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 3
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 3
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 3
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 3
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 3
- 102100036305 C-C chemokine receptor type 8 Human genes 0.000 description 3
- 102100025074 C-C chemokine receptor-like 2 Human genes 0.000 description 3
- 102100036842 C-C motif chemokine 19 Human genes 0.000 description 3
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 3
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 3
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 3
- 102100036189 C-X-C motif chemokine 3 Human genes 0.000 description 3
- 102100032976 CCR4-NOT transcription complex subunit 6 Human genes 0.000 description 3
- 102100032937 CD40 ligand Human genes 0.000 description 3
- 108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 description 3
- 102100039196 CX3C chemokine receptor 1 Human genes 0.000 description 3
- 101100504320 Caenorhabditis elegans mcp-1 gene Proteins 0.000 description 3
- 102100025632 Caspase recruitment domain-containing protein 18 Human genes 0.000 description 3
- 102100035294 Chemokine XC receptor 1 Human genes 0.000 description 3
- 102000019034 Chemokines Human genes 0.000 description 3
- 108010012236 Chemokines Proteins 0.000 description 3
- 102100033772 Complement C4-A Human genes 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 102100034221 Growth-regulated alpha protein Human genes 0.000 description 3
- 101000783783 Homo sapiens ATP-binding cassette sub-family F member 1 Proteins 0.000 description 3
- 101000755762 Homo sapiens Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 Proteins 0.000 description 3
- 101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 description 3
- 101000971234 Homo sapiens B-cell lymphoma 6 protein Proteins 0.000 description 3
- 101000716068 Homo sapiens C-C chemokine receptor type 6 Proteins 0.000 description 3
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 3
- 101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 description 3
- 101000716070 Homo sapiens C-C chemokine receptor type 9 Proteins 0.000 description 3
- 101000713106 Homo sapiens C-C motif chemokine 19 Proteins 0.000 description 3
- 101000713085 Homo sapiens C-C motif chemokine 21 Proteins 0.000 description 3
- 101000897493 Homo sapiens C-C motif chemokine 26 Proteins 0.000 description 3
- 101000797762 Homo sapiens C-C motif chemokine 5 Proteins 0.000 description 3
- 101000797758 Homo sapiens C-C motif chemokine 7 Proteins 0.000 description 3
- 101000916059 Homo sapiens C-X-C chemokine receptor type 2 Proteins 0.000 description 3
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 3
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 3
- 101000947193 Homo sapiens C-X-C motif chemokine 3 Proteins 0.000 description 3
- 101000947177 Homo sapiens C-X-C motif chemokine 6 Proteins 0.000 description 3
- 101000947172 Homo sapiens C-X-C motif chemokine 9 Proteins 0.000 description 3
- 101000945963 Homo sapiens CCAAT/enhancer-binding protein beta Proteins 0.000 description 3
- 101000933105 Homo sapiens Caspase recruitment domain-containing protein 18 Proteins 0.000 description 3
- 101000804783 Homo sapiens Chemokine XC receptor 1 Proteins 0.000 description 3
- 101000710884 Homo sapiens Complement C4-A Proteins 0.000 description 3
- 101000978392 Homo sapiens Eotaxin Proteins 0.000 description 3
- 101001002634 Homo sapiens Interleukin-1 alpha Proteins 0.000 description 3
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 3
- 101001076386 Homo sapiens Interleukin-1 family member 10 Proteins 0.000 description 3
- 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 3
- 101001076418 Homo sapiens Interleukin-1 receptor type 1 Proteins 0.000 description 3
- 101001083151 Homo sapiens Interleukin-10 receptor subunit alpha Proteins 0.000 description 3
- 101001003149 Homo sapiens Interleukin-10 receptor subunit beta Proteins 0.000 description 3
- 101000998178 Homo sapiens Interleukin-17C Proteins 0.000 description 3
- 101001010626 Homo sapiens Interleukin-22 Proteins 0.000 description 3
- 101000998140 Homo sapiens Interleukin-36 alpha Proteins 0.000 description 3
- 101000998126 Homo sapiens Interleukin-36 beta Proteins 0.000 description 3
- 101001040964 Homo sapiens Interleukin-36 receptor antagonist protein Proteins 0.000 description 3
- 101000998122 Homo sapiens Interleukin-37 Proteins 0.000 description 3
- 101001017968 Homo sapiens Leukotriene B4 receptor 1 Proteins 0.000 description 3
- 101000764535 Homo sapiens Lymphotoxin-alpha Proteins 0.000 description 3
- 101000764294 Homo sapiens Lymphotoxin-beta Proteins 0.000 description 3
- 101000830560 Homo sapiens Toll-interacting protein Proteins 0.000 description 3
- 108091058536 IL1F9 Proteins 0.000 description 3
- 102100020881 Interleukin-1 alpha Human genes 0.000 description 3
- 102100039065 Interleukin-1 beta Human genes 0.000 description 3
- 102100026015 Interleukin-1 family member 10 Human genes 0.000 description 3
- 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 3
- 102100026016 Interleukin-1 receptor type 1 Human genes 0.000 description 3
- 102000003814 Interleukin-10 Human genes 0.000 description 3
- 108090000174 Interleukin-10 Proteins 0.000 description 3
- 102100030236 Interleukin-10 receptor subunit alpha Human genes 0.000 description 3
- 102100020788 Interleukin-10 receptor subunit beta Human genes 0.000 description 3
- 102100033105 Interleukin-17C Human genes 0.000 description 3
- 102100033474 Interleukin-36 alpha Human genes 0.000 description 3
- 102100033498 Interleukin-36 beta Human genes 0.000 description 3
- 102100033503 Interleukin-36 gamma Human genes 0.000 description 3
- 102100021150 Interleukin-36 receptor antagonist protein Human genes 0.000 description 3
- 206010024264 Lethargy Diseases 0.000 description 3
- 102100033374 Leukotriene B4 receptor 1 Human genes 0.000 description 3
- 101001089108 Lotus tetragonolobus Anti-H(O) lectin Proteins 0.000 description 3
- 102100026238 Lymphotoxin-alpha Human genes 0.000 description 3
- 102100026894 Lymphotoxin-beta Human genes 0.000 description 3
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 3
- 101000718529 Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2) Alpha-galactosidase Proteins 0.000 description 3
- 101710168942 Sphingosine-1-phosphate phosphatase 1 Proteins 0.000 description 3
- 101710088580 Stromal cell-derived factor 1 Proteins 0.000 description 3
- 102100024652 Toll-interacting protein Human genes 0.000 description 3
- 230000003044 adaptive effect Effects 0.000 description 3
- NNISLDGFPWIBDF-MPRBLYSKSA-N alpha-D-Gal-(1->3)-beta-D-Gal-(1->4)-D-GlcNAc Chemical compound O[C@@H]1[C@@H](NC(=O)C)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@@H](CO)O1 NNISLDGFPWIBDF-MPRBLYSKSA-N 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 208000022379 autosomal dominant Opitz G/BBB syndrome Diseases 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 230000003492 excitotoxic effect Effects 0.000 description 3
- 231100000063 excitotoxicity Toxicity 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 210000003016 hypothalamus Anatomy 0.000 description 3
- 230000002519 immonomodulatory effect Effects 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 239000003226 mitogen Substances 0.000 description 3
- 239000001272 nitrous oxide Substances 0.000 description 3
- 229960001476 pentoxifylline Drugs 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 208000020016 psychiatric disease Diseases 0.000 description 3
- 229940001470 psychoactive drug Drugs 0.000 description 3
- 239000004089 psychotropic agent Substances 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000003252 repetitive effect Effects 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 2
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 2
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000032467 Aplastic anaemia Diseases 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
- 208000020925 Bipolar disease Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102100034871 C-C motif chemokine 8 Human genes 0.000 description 2
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 2
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 2
- 206010051288 Central nervous system inflammation Diseases 0.000 description 2
- 102000016950 Chemokine CXCL1 Human genes 0.000 description 2
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 description 2
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 2
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 2
- 102100037241 Endoglin Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010014612 Follistatin Proteins 0.000 description 2
- 102000016970 Follistatin Human genes 0.000 description 2
- 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 2
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 2
- 101000946794 Homo sapiens C-C motif chemokine 8 Proteins 0.000 description 2
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 2
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 2
- 101000868215 Homo sapiens CD40 ligand Proteins 0.000 description 2
- 101001069921 Homo sapiens Growth-regulated alpha protein Proteins 0.000 description 2
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 description 2
- 101001003135 Homo sapiens Interleukin-13 receptor subunit alpha-1 Proteins 0.000 description 2
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 2
- 101000868152 Homo sapiens Son of sevenless homolog 1 Proteins 0.000 description 2
- 101100369992 Homo sapiens TNFSF10 gene Proteins 0.000 description 2
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 2
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 2
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 2
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 102000014158 Interleukin-12 Subunit p40 Human genes 0.000 description 2
- 108010011429 Interleukin-12 Subunit p40 Proteins 0.000 description 2
- 102100020791 Interleukin-13 receptor subunit alpha-1 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102100026019 Interleukin-6 Human genes 0.000 description 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 2
- 206010061285 Mental disorder due to a general medical condition Diseases 0.000 description 2
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 2
- 101710151803 Mitochondrial intermediate peptidase 2 Proteins 0.000 description 2
- 208000029726 Neurodevelopmental disease Diseases 0.000 description 2
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 102000046283 TNF-Related Apoptosis-Inducing Ligand Human genes 0.000 description 2
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 description 2
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 2
- NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical compound CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 229940125681 anticonvulsant agent Drugs 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 208000013404 behavioral symptom Diseases 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003433 contraceptive agent Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 238000003255 drug test Methods 0.000 description 2
- 201000002491 encephalomyelitis Diseases 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 208000037870 generalized anxiety Diseases 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000008938 immune dysregulation Effects 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 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 2
- 239000003446 ligand Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 210000005170 neoplastic cell Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000003959 neuroinflammation Effects 0.000 description 2
- 208000019906 panic disease Diseases 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 229960005095 pioglitazone Drugs 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000009597 pregnancy test Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 210000003289 regulatory T cell Anatomy 0.000 description 2
- 208000013406 repetitive behavior Diseases 0.000 description 2
- 230000003989 repetitive behavior Effects 0.000 description 2
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 2
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 2
- 230000004006 stereotypic behavior Effects 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- 210000001103 thalamus Anatomy 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000009529 traumatic brain injury Effects 0.000 description 2
- JPSHPWJJSVEEAX-OWPBQMJCSA-N (2s)-2-amino-4-fluoranylpentanedioic acid Chemical compound OC(=O)[C@@H](N)CC([18F])C(O)=O JPSHPWJJSVEEAX-OWPBQMJCSA-N 0.000 description 1
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 1
- PHIQHXFUZVPYII-ZCFIWIBFSA-O (R)-carnitinium Chemical compound C[N+](C)(C)C[C@H](O)CC(O)=O PHIQHXFUZVPYII-ZCFIWIBFSA-O 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 1
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 description 1
- 102100021546 60S ribosomal protein L10 Human genes 0.000 description 1
- 102100023990 60S ribosomal protein L17 Human genes 0.000 description 1
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 1
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 1
- 108010075348 Activated-Leukocyte Cell Adhesion Molecule Proteins 0.000 description 1
- 102100026423 Adhesion G protein-coupled receptor E5 Human genes 0.000 description 1
- 208000008811 Agoraphobia Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 102100023635 Alpha-fetoprotein Human genes 0.000 description 1
- 102100022987 Angiogenin Human genes 0.000 description 1
- 108010048154 Angiopoietin-1 Proteins 0.000 description 1
- 102000009088 Angiopoietin-1 Human genes 0.000 description 1
- 102100034608 Angiopoietin-2 Human genes 0.000 description 1
- 108010048036 Angiopoietin-2 Proteins 0.000 description 1
- 102100033402 Angiopoietin-4 Human genes 0.000 description 1
- 102000030431 Asparaginyl endopeptidase Human genes 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 description 1
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102100028239 Basal cell adhesion molecule Human genes 0.000 description 1
- 108010081589 Becaplermin Proteins 0.000 description 1
- 101800001382 Betacellulin Proteins 0.000 description 1
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 1
- 108010049955 Bone Morphogenetic Protein 4 Proteins 0.000 description 1
- 108010049976 Bone Morphogenetic Protein 5 Proteins 0.000 description 1
- 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 description 1
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 1
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 1
- 102100022526 Bone morphogenetic protein 5 Human genes 0.000 description 1
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 1
- 101001027327 Bos taurus Growth-regulated protein homolog alpha Proteins 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- 101710112613 C-C motif chemokine 13 Proteins 0.000 description 1
- 102100023705 C-C motif chemokine 14 Human genes 0.000 description 1
- 102100021936 C-C motif chemokine 27 Human genes 0.000 description 1
- 101710112538 C-C motif chemokine 27 Proteins 0.000 description 1
- 102100021942 C-C motif chemokine 28 Human genes 0.000 description 1
- 101710155834 C-C motif chemokine 7 Proteins 0.000 description 1
- 102100039396 C-X-C motif chemokine 16 Human genes 0.000 description 1
- 101710085500 C-X-C motif chemokine 9 Proteins 0.000 description 1
- 101710134031 CCAAT/enhancer-binding protein beta Proteins 0.000 description 1
- 102100031173 CCN family member 4 Human genes 0.000 description 1
- 101710137353 CCN family member 4 Proteins 0.000 description 1
- 108010009992 CD163 antigen Proteins 0.000 description 1
- 102100024210 CD166 antigen Human genes 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 101150093802 CXCL1 gene Proteins 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 1
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102400001321 Cathepsin L Human genes 0.000 description 1
- 108090000624 Cathepsin L Proteins 0.000 description 1
- 102100035654 Cathepsin S Human genes 0.000 description 1
- 108090000613 Cathepsin S Proteins 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 108010082548 Chemokine CCL11 Proteins 0.000 description 1
- 108010083702 Chemokine CCL21 Proteins 0.000 description 1
- 108010083698 Chemokine CCL26 Proteins 0.000 description 1
- 108010014419 Chemokine CXCL1 Proteins 0.000 description 1
- 208000004051 Chronic Traumatic Encephalopathy Diseases 0.000 description 1
- 206010009244 Claustrophobia Diseases 0.000 description 1
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 102100032887 Clusterin Human genes 0.000 description 1
- 108090000197 Clusterin Proteins 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 102100027995 Collagenase 3 Human genes 0.000 description 1
- 108050005238 Collagenase 3 Proteins 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 102100031506 Complement C5 Human genes 0.000 description 1
- 102000003706 Complement factor D Human genes 0.000 description 1
- 108090000059 Complement factor D Proteins 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 101150031350 Cxcl2 gene Proteins 0.000 description 1
- 102000012192 Cystatin C Human genes 0.000 description 1
- 108010061642 Cystatin C Proteins 0.000 description 1
- 102000005754 Cytokine Receptor gp130 Human genes 0.000 description 1
- 108010006197 Cytokine Receptor gp130 Proteins 0.000 description 1
- 101710199286 Cytosol aminopeptidase Proteins 0.000 description 1
- 102100027816 Cytotoxic and regulatory T-cell molecule Human genes 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 1
- 102100035784 Decorin Human genes 0.000 description 1
- 108090000738 Decorin Proteins 0.000 description 1
- 102100036462 Delta-like protein 1 Human genes 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 206010054089 Depressive symptom Diseases 0.000 description 1
- 206010012559 Developmental delay Diseases 0.000 description 1
- 102100030074 Dickkopf-related protein 1 Human genes 0.000 description 1
- 101710099518 Dickkopf-related protein 1 Proteins 0.000 description 1
- 102100037985 Dickkopf-related protein 3 Human genes 0.000 description 1
- 101710099550 Dickkopf-related protein 3 Proteins 0.000 description 1
- 102100031107 Disintegrin and metalloproteinase domain-containing protein 11 Human genes 0.000 description 1
- 101710121366 Disintegrin and metalloproteinase domain-containing protein 11 Proteins 0.000 description 1
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 1
- 102100024361 Disintegrin and metalloproteinase domain-containing protein 9 Human genes 0.000 description 1
- 101710116121 Disintegrin and metalloproteinase domain-containing protein 9 Proteins 0.000 description 1
- 101100120663 Drosophila melanogaster fs(1)h gene Proteins 0.000 description 1
- 108010024212 E-Selectin Proteins 0.000 description 1
- 102100023471 E-selectin Human genes 0.000 description 1
- 101710197780 E3 ubiquitin-protein ligase LAP Proteins 0.000 description 1
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 1
- 102100023795 Elafin Human genes 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 108010044063 Endocrine-Gland-Derived Vascular Endothelial Growth Factor Proteins 0.000 description 1
- 108010036395 Endoglin Proteins 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 1
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 1
- 102100026748 Fatty acid-binding protein, intestinal Human genes 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 102100031734 Fibroblast growth factor 19 Human genes 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 description 1
- 108090000381 Fibroblast growth factor 4 Proteins 0.000 description 1
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 description 1
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 102100035139 Folate receptor alpha Human genes 0.000 description 1
- 102100035233 Furin Human genes 0.000 description 1
- 108090001126 Furin Proteins 0.000 description 1
- 101710142641 G-protein coupled receptor-associated sorting protein 1 Proteins 0.000 description 1
- 101710142639 G-protein coupled receptor-associated sorting protein 2 Proteins 0.000 description 1
- 108010001517 Galectin 3 Proteins 0.000 description 1
- 102100039558 Galectin-3 Human genes 0.000 description 1
- 102000044465 Galectin-7 Human genes 0.000 description 1
- 102100028652 Gamma-enolase Human genes 0.000 description 1
- 101710191797 Gamma-enolase Proteins 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 206010071602 Genetic polymorphism Diseases 0.000 description 1
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 1
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 1
- 101710088083 Glomulin Proteins 0.000 description 1
- 229940122459 Glutamate antagonist Drugs 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 108010041834 Growth Differentiation Factor 15 Proteins 0.000 description 1
- 108010090290 Growth Differentiation Factor 2 Proteins 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 102100040896 Growth/differentiation factor 15 Human genes 0.000 description 1
- 102100040892 Growth/differentiation factor 2 Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 description 1
- 102400001369 Heparin-binding EGF-like growth factor Human genes 0.000 description 1
- 108010007712 Hepatitis A Virus Cellular Receptor 1 Proteins 0.000 description 1
- 102100034459 Hepatitis A virus cellular receptor 1 Human genes 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001108634 Homo sapiens 60S ribosomal protein L10 Proteins 0.000 description 1
- 101000718243 Homo sapiens Adhesion G protein-coupled receptor E5 Proteins 0.000 description 1
- 101000935638 Homo sapiens Basal cell adhesion molecule Proteins 0.000 description 1
- 101000766294 Homo sapiens Branched-chain-amino-acid aminotransferase, mitochondrial Proteins 0.000 description 1
- 101000978381 Homo sapiens C-C motif chemokine 14 Proteins 0.000 description 1
- 101000897477 Homo sapiens C-C motif chemokine 28 Proteins 0.000 description 1
- 101000889133 Homo sapiens C-X-C motif chemokine 16 Proteins 0.000 description 1
- 101000777555 Homo sapiens CCN family member 3 Proteins 0.000 description 1
- 101000941598 Homo sapiens Complement C5 Proteins 0.000 description 1
- 101000856395 Homo sapiens Cullin-9 Proteins 0.000 description 1
- 101000928537 Homo sapiens Delta-like protein 1 Proteins 0.000 description 1
- 101000777461 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 17 Proteins 0.000 description 1
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 1
- 101001048718 Homo sapiens Elafin Proteins 0.000 description 1
- 101000911337 Homo sapiens Fatty acid-binding protein, intestinal Proteins 0.000 description 1
- 101000846394 Homo sapiens Fibroblast growth factor 19 Proteins 0.000 description 1
- 101001023230 Homo sapiens Folate receptor alpha Proteins 0.000 description 1
- 101000608772 Homo sapiens Galectin-7 Proteins 0.000 description 1
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 1
- 101001002470 Homo sapiens Interferon lambda-1 Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101000852968 Homo sapiens Interleukin-1 receptor-like 1 Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101000716481 Homo sapiens Lysosome membrane protein 2 Proteins 0.000 description 1
- 101000991061 Homo sapiens MHC class I polypeptide-related sequence B Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000602237 Homo sapiens Neuroblastoma suppressor of tumorigenicity 1 Proteins 0.000 description 1
- 101000973997 Homo sapiens Nucleosome assembly protein 1-like 4 Proteins 0.000 description 1
- 101001098352 Homo sapiens OX-2 membrane glycoprotein Proteins 0.000 description 1
- 101001001487 Homo sapiens Phosphatidylinositol-glycan biosynthesis class F protein Proteins 0.000 description 1
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 1
- 101000947178 Homo sapiens Platelet basic protein Proteins 0.000 description 1
- 101000582950 Homo sapiens Platelet factor 4 Proteins 0.000 description 1
- 101001067189 Homo sapiens Plexin-A1 Proteins 0.000 description 1
- 101001113490 Homo sapiens Poly(A)-specific ribonuclease PARN Proteins 0.000 description 1
- 101000665882 Homo sapiens Retinol-binding protein 4 Proteins 0.000 description 1
- 101000711796 Homo sapiens Sclerostin Proteins 0.000 description 1
- 101000863883 Homo sapiens Sialic acid-binding Ig-like lectin 9 Proteins 0.000 description 1
- 101000585365 Homo sapiens Sulfotransferase 2A1 Proteins 0.000 description 1
- 101000835745 Homo sapiens Teratocarcinoma-derived growth factor 1 Proteins 0.000 description 1
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 1
- 101000845170 Homo sapiens Thymic stromal lymphopoietin Proteins 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- 101000904724 Homo sapiens Transmembrane glycoprotein NMB Proteins 0.000 description 1
- 101000795167 Homo sapiens Tumor necrosis factor receptor superfamily member 13B Proteins 0.000 description 1
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 1
- 101000597785 Homo sapiens Tumor necrosis factor receptor superfamily member 6B Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 101710123134 Ice-binding protein Proteins 0.000 description 1
- 101710082837 Ice-structuring protein Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004372 Insulin-like growth factor binding protein 2 Human genes 0.000 description 1
- 108090000964 Insulin-like growth factor binding protein 2 Proteins 0.000 description 1
- 102000004374 Insulin-like growth factor binding protein 3 Human genes 0.000 description 1
- 108090000965 Insulin-like growth factor binding protein 3 Proteins 0.000 description 1
- 102000004369 Insulin-like growth factor-binding protein 4 Human genes 0.000 description 1
- 108090000969 Insulin-like growth factor-binding protein 4 Proteins 0.000 description 1
- 102000004883 Insulin-like growth factor-binding protein 6 Human genes 0.000 description 1
- 108090001014 Insulin-like growth factor-binding protein 6 Proteins 0.000 description 1
- 201000006347 Intellectual Disability Diseases 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 108010064600 Intercellular Adhesion Molecule-3 Proteins 0.000 description 1
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
- 102100037872 Intercellular adhesion molecule 2 Human genes 0.000 description 1
- 101710148794 Intercellular adhesion molecule 2 Proteins 0.000 description 1
- 102100037871 Intercellular adhesion molecule 3 Human genes 0.000 description 1
- 102100020990 Interferon lambda-1 Human genes 0.000 description 1
- 102100020989 Interferon lambda-2 Human genes 0.000 description 1
- 101710099622 Interferon lambda-2 Proteins 0.000 description 1
- 101800003050 Interleukin-16 Proteins 0.000 description 1
- 102000049772 Interleukin-16 Human genes 0.000 description 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 1
- 108010065637 Interleukin-23 Proteins 0.000 description 1
- 108010066979 Interleukin-27 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 102100021596 Interleukin-31 Human genes 0.000 description 1
- 101710181613 Interleukin-31 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 102000000704 Interleukin-7 Human genes 0.000 description 1
- 108020003285 Isocitrate lyase Proteins 0.000 description 1
- 102100023437 Junctional adhesion molecule-like Human genes 0.000 description 1
- 102100038298 Kallikrein-14 Human genes 0.000 description 1
- 101710115806 Kallikrein-14 Proteins 0.000 description 1
- 102100023012 Kallistatin Human genes 0.000 description 1
- 102100020880 Kit ligand Human genes 0.000 description 1
- 101710177504 Kit ligand Proteins 0.000 description 1
- 102100039020 Kunitz-type protease inhibitor 2 Human genes 0.000 description 1
- 101710165138 Kunitz-type protease inhibitor 2 Proteins 0.000 description 1
- 108010092694 L-Selectin Proteins 0.000 description 1
- 102100033467 L-selectin Human genes 0.000 description 1
- 102000017578 LAG3 Human genes 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 101150030213 Lag3 gene Proteins 0.000 description 1
- 208000020358 Learning disease Diseases 0.000 description 1
- 102100032352 Leukemia inhibitory factor Human genes 0.000 description 1
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 1
- 102000013519 Lipocalin-2 Human genes 0.000 description 1
- 108010051335 Lipocalin-2 Proteins 0.000 description 1
- 102100026849 Lymphatic vessel endothelial hyaluronic acid receptor 1 Human genes 0.000 description 1
- 101710178181 Lymphatic vessel endothelial hyaluronic acid receptor 1 Proteins 0.000 description 1
- 102100035304 Lymphotactin Human genes 0.000 description 1
- 101710204480 Lysosomal acid phosphatase Proteins 0.000 description 1
- 102100020983 Lysosome membrane protein 2 Human genes 0.000 description 1
- 102100030301 MHC class I polypeptide-related sequence A Human genes 0.000 description 1
- 102100030300 MHC class I polypeptide-related sequence B Human genes 0.000 description 1
- 108010064699 MSH Release-Inhibiting Hormone Proteins 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 102100026553 Mannose-binding protein C Human genes 0.000 description 1
- 101710110798 Mannose-binding protein C Proteins 0.000 description 1
- 102100027754 Mast/stem cell growth factor receptor Kit Human genes 0.000 description 1
- 101710087603 Mast/stem cell growth factor receptor Kit Proteins 0.000 description 1
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 1
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- NOOJLZTTWSNHOX-UWVGGRQHSA-N Melanostatin Chemical compound NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 NOOJLZTTWSNHOX-UWVGGRQHSA-N 0.000 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 description 1
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 1
- 102100026262 Metalloproteinase inhibitor 2 Human genes 0.000 description 1
- 102100024289 Metalloproteinase inhibitor 4 Human genes 0.000 description 1
- 108050006579 Metalloproteinase inhibitor 4 Proteins 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 101100262697 Mus musculus Axl gene Proteins 0.000 description 1
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 1
- 101000904718 Mus musculus Transmembrane glycoprotein NMB Proteins 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 102000047918 Myelin Basic Human genes 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 102100031789 Myeloid-derived growth factor Human genes 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 101150031836 NRCAM gene Proteins 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 108050003738 Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 102100023181 Neurogenic locus notch homolog protein 1 Human genes 0.000 description 1
- 108700037638 Neurogenic locus notch homolog protein 1 Proteins 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 102100030411 Neutrophil collagenase Human genes 0.000 description 1
- 101710118230 Neutrophil collagenase Proteins 0.000 description 1
- 102100037369 Nidogen-1 Human genes 0.000 description 1
- 102100037589 OX-2 membrane glycoprotein Human genes 0.000 description 1
- 206010029897 Obsessive thoughts Diseases 0.000 description 1
- 108090000630 Oncostatin M Proteins 0.000 description 1
- 102100031942 Oncostatin-M Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 102100025386 Oxidized low-density lipoprotein receptor 1 Human genes 0.000 description 1
- 101710199789 Oxidized low-density lipoprotein receptor 1 Proteins 0.000 description 1
- 102400000050 Oxytocin Human genes 0.000 description 1
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 1
- 101800000989 Oxytocin Proteins 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010033664 Panic attack Diseases 0.000 description 1
- 108010047320 Pepsinogen A Proteins 0.000 description 1
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
- 102100021768 Phosphoserine aminotransferase Human genes 0.000 description 1
- 102100035194 Placenta growth factor Human genes 0.000 description 1
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 1
- 108010069381 Platelet Endothelial Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 102100036154 Platelet basic protein Human genes 0.000 description 1
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
- 102100030304 Platelet factor 4 Human genes 0.000 description 1
- 108010033737 Pokeweed Mitogens Proteins 0.000 description 1
- 102100023715 Poly(A)-specific ribonuclease PARN Human genes 0.000 description 1
- 101710098940 Pro-epidermal growth factor Proteins 0.000 description 1
- 101710089118 Probable cytosol aminopeptidase Proteins 0.000 description 1
- 102100029837 Probetacellulin Human genes 0.000 description 1
- 108010048233 Procalcitonin Proteins 0.000 description 1
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 1
- 102100040126 Prokineticin-1 Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 102100024819 Prolactin Human genes 0.000 description 1
- 102100023832 Prolyl endopeptidase FAP Human genes 0.000 description 1
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 102000014128 RANK Ligand Human genes 0.000 description 1
- 108010025832 RANK Ligand Proteins 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102000007156 Resistin Human genes 0.000 description 1
- 108010047909 Resistin Proteins 0.000 description 1
- 102100033914 Retinoic acid receptor responder protein 2 Human genes 0.000 description 1
- 101710170513 Retinoic acid receptor responder protein 2 Proteins 0.000 description 1
- 102100038246 Retinol-binding protein 4 Human genes 0.000 description 1
- 102100025831 Scavenger receptor cysteine-rich type 1 protein M130 Human genes 0.000 description 1
- 102100034201 Sclerostin Human genes 0.000 description 1
- 102100030053 Secreted frizzled-related protein 3 Human genes 0.000 description 1
- 108050007990 Secreted frizzled-related protein 3 Proteins 0.000 description 1
- 101710110535 Sialic acid-binding Ig-like lectin 5 Proteins 0.000 description 1
- 102100029957 Sialic acid-binding Ig-like lectin 5 Human genes 0.000 description 1
- 102100029965 Sialic acid-binding Ig-like lectin 9 Human genes 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 206010041243 Social avoidant behaviour Diseases 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 102400000673 Sonic hedgehog protein N-product Human genes 0.000 description 1
- 101800001400 Sonic hedgehog protein N-product Proteins 0.000 description 1
- 102100030416 Stromelysin-1 Human genes 0.000 description 1
- 101710108790 Stromelysin-1 Proteins 0.000 description 1
- 102100028848 Stromelysin-2 Human genes 0.000 description 1
- 101710108792 Stromelysin-2 Proteins 0.000 description 1
- 102100029867 Sulfotransferase 2A1 Human genes 0.000 description 1
- 102000003705 Syndecan-1 Human genes 0.000 description 1
- 108090000058 Syndecan-1 Proteins 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102100026404 Teratocarcinoma-derived growth factor 1 Human genes 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 description 1
- 102100026966 Thrombomodulin Human genes 0.000 description 1
- 108010079274 Thrombomodulin Proteins 0.000 description 1
- 102000007614 Thrombospondin 1 Human genes 0.000 description 1
- 108010046722 Thrombospondin 1 Proteins 0.000 description 1
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 1
- 102100031294 Thymic stromal lymphopoietin Human genes 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 description 1
- 108010031372 Tissue Inhibitor of Metalloproteinase-2 Proteins 0.000 description 1
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 1
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 108010066451 Triggering Receptor Expressed on Myeloid Cells-1 Proteins 0.000 description 1
- 102100029681 Triggering receptor expressed on myeloid cells 1 Human genes 0.000 description 1
- BMQYVXCPAOLZOK-UHFFFAOYSA-N Trihydroxypropylpterisin Natural products OCC(O)C(O)C1=CN=C2NC(N)=NC(=O)C2=N1 BMQYVXCPAOLZOK-UHFFFAOYSA-N 0.000 description 1
- 102000013394 Troponin I Human genes 0.000 description 1
- 108010065729 Troponin I Proteins 0.000 description 1
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 1
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 1
- 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 1
- 102100029675 Tumor necrosis factor receptor superfamily member 13B Human genes 0.000 description 1
- 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 1
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 102100035284 Tumor necrosis factor receptor superfamily member 6B Human genes 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 101710107540 Type-2 ice-structuring protein Proteins 0.000 description 1
- 102100031358 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 102000008790 VE-cadherin Human genes 0.000 description 1
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 1
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 1
- 102100038232 Vascular endothelial growth factor C Human genes 0.000 description 1
- 102100038234 Vascular endothelial growth factor D Human genes 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 102100020722 WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 1 Human genes 0.000 description 1
- 101710160039 WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 1 Proteins 0.000 description 1
- 102100036021 WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 Human genes 0.000 description 1
- 101710160038 WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000001467 acupuncture Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000003915 air pollution Methods 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 102000012005 alpha-2-HS-Glycoprotein Human genes 0.000 description 1
- 108010075843 alpha-2-HS-Glycoprotein Proteins 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 239000003194 amino acid receptor blocking agent Substances 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 108010072788 angiogenin Proteins 0.000 description 1
- 108010069801 angiopoietin 4 Proteins 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 238000011861 anti-inflammatory therapy Methods 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 208000024823 antisocial personality disease Diseases 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 108010055066 asparaginylendopeptidase Proteins 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 201000007197 atypical autism Diseases 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 231100000871 behavioral problem Toxicity 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 101150020997 bpa gene Proteins 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 108010018828 cadherin 5 Proteins 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
- 229960000623 carbamazepine Drugs 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 210000001159 caudate nucleus Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 206010008129 cerebral palsy Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- YRQNKMKHABXEJZ-UVQQGXFZSA-N chembl176323 Chemical compound C1C[C@]2(C)[C@@]3(C)CC(N=C4C[C@]5(C)CCC6[C@]7(C)CC[C@@H]([C@]7(CC[C@]6(C)[C@@]5(C)CC4=N4)C)CCCCCCCC)=C4C[C@]3(C)CCC2[C@]2(C)CC[C@H](CCCCCCCC)[C@]21C YRQNKMKHABXEJZ-UVQQGXFZSA-N 0.000 description 1
- 230000014564 chemokine production Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 description 1
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
- 229960001076 chlorpromazine Drugs 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 230000037326 chronic stress Effects 0.000 description 1
- 108010072917 class-I restricted T cell-associated molecule Proteins 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 229960004606 clomipramine Drugs 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 208000030251 communication disease Diseases 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229940124558 contraceptive agent Drugs 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 235000019788 craving Nutrition 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 208000017004 dementia pugilistica Diseases 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- MDCUNMLZLNGCQA-HWOAGHQOSA-N elafin Chemical compound N([C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H]1C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H]2CSSC[C@H]3C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](CSSC[C@H]4C(=O)N5CCC[C@H]5C(=O)NCC(=O)N[C@H](C(N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H]5N(CCC5)C(=O)[C@H]5N(CCC5)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC2=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N4)C(=O)N[C@@H](CSSC1)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N3)=O)[C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(O)=O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)C(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)N MDCUNMLZLNGCQA-HWOAGHQOSA-N 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 210000003060 endolymph Anatomy 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 230000010437 erythropoiesis Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 229960004038 fluvoxamine Drugs 0.000 description 1
- CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 1
- 230000009760 functional impairment Effects 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000021312 gluten Nutrition 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 238000002639 hyperbaric oxygen therapy Methods 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000006057 immunotolerant effect Effects 0.000 description 1
- 208000026762 inability to speak Diseases 0.000 description 1
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000018276 interleukin-1 production Effects 0.000 description 1
- 229940076144 interleukin-10 Drugs 0.000 description 1
- 102000053460 interleukin-17 receptor activity proteins Human genes 0.000 description 1
- 108040001304 interleukin-17 receptor activity proteins Proteins 0.000 description 1
- 108010074108 interleukin-21 Proteins 0.000 description 1
- 102000008640 interleukin-21 receptor activity proteins Human genes 0.000 description 1
- 108040002099 interleukin-21 receptor activity proteins Proteins 0.000 description 1
- 108090000237 interleukin-24 Proteins 0.000 description 1
- 102000003898 interleukin-24 Human genes 0.000 description 1
- 230000017306 interleukin-6 production Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 108010050180 kallistatin Proteins 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 229960001848 lamotrigine Drugs 0.000 description 1
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 210000004558 lewy body Anatomy 0.000 description 1
- 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 108010019677 lymphotactin Proteins 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 229960004023 minocycline Drugs 0.000 description 1
- 230000004065 mitochondrial dysfunction Effects 0.000 description 1
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
- 238000000051 music therapy Methods 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 description 1
- 229960003086 naltrexone Drugs 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- BMQYVXCPAOLZOK-XINAWCOVSA-N neopterin Chemical compound OC[C@@H](O)[C@@H](O)C1=CN=C2NC(N)=NC(=O)C2=N1 BMQYVXCPAOLZOK-XINAWCOVSA-N 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 108010008217 nidogen Proteins 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 230000007959 normoxia Effects 0.000 description 1
- 229940127234 oral contraceptive Drugs 0.000 description 1
- 239000003539 oral contraceptive agent Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 1
- 229960001723 oxytocin Drugs 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 210000004049 perilymph Anatomy 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 1
- 108010000685 platelet-derived growth factor AB Proteins 0.000 description 1
- 230000015284 positive regulation of neurogenesis Effects 0.000 description 1
- CWCXERYKLSEGEZ-KDKHKZEGSA-N procalcitonin Chemical compound C([C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(O)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H]1NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H](N)CSSC1)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 CWCXERYKLSEGEZ-KDKHKZEGSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 210000000449 purkinje cell Anatomy 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001373 regressive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 description 1
- 229960004617 sapropterin Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- CJUDSKIRZCSXJA-UHFFFAOYSA-M sodium;3-(n-ethyl-3-methoxyanilino)-2-hydroxypropane-1-sulfonate Chemical compound [Na+].[O-]S(=O)(=O)CC(O)CN(CC)C1=CC=CC(OC)=C1 CJUDSKIRZCSXJA-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000027765 speech disease Diseases 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000009168 stem cell therapy Methods 0.000 description 1
- 238000009580 stem-cell therapy Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 210000003478 temporal lobe Anatomy 0.000 description 1
- 229960002784 thioridazine Drugs 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- 230000020192 tolerance induction in gut-associated lymphoid tissue Effects 0.000 description 1
- 230000017756 tolerance induction in nasopharyngeal-associated lymphoid tissue Effects 0.000 description 1
- 229960004394 topiramate Drugs 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 108040001269 urokinase plasminogen activator receptor activity proteins Proteins 0.000 description 1
- 102000009816 urokinase plasminogen activator receptor activity proteins Human genes 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pulmonology (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Otolaryngology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Inorganic Chemistry (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Cell Biology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
本出願は、参照としてその全体が本明細書に援用される2015年6月23日出願の米国仮特許出願第62/183,624号、2016年1月8日出願の米国仮特許出願第62/276,753号の優先権を主張する。
本発明は、全身性および中枢神経系において局所性に生じる炎症性サイトカインを減少させるために希ガス含有混合物の使用を教示する。 本発明の1つの態様において、希ガス含有組成物の投与後のインターフェロンガンマ、IL−12およびIL−17の減少を開示する。 1つの態様において、本発明は、炎症性サイトカインの産生が関連する病状を患う個体に投与される希ガス含有組成物の強度と持続時間を定量化する手段として、これらのサイトカインの全身レベルにおける評価を提供する。 1つの態様において、本発明は、希ガス含有組成物を使用する治療介入の必要性を示す指標として、マイトジェンによるex vivoの刺激後に末梢血単核細胞によって産生される炎症性サイトカイン・レベルの評価を教示する。 1つの特定の実施態様では、自閉症および自閉症スペクトラム障害の病状に対して、炎症性サイトカイン産生の評価およびそれに続く希ガス含有組成物の投与による調節が行われる。 1つの実施態様において、前記炎症性サイトカインが、 ABCF1、BCL6、C3、C4A、CEBPB、CRP、ICEBERG、IL1R1、IL1RN、IL8RB、LTB4R、TOLLIP、IFNA2、IL10RA、IL10RB、IL13、IL13RA1、IL5RA、IL9、IL9R、CD40LG(TNFSF5)、IFNA2、IL17C、IL1A、IL1B、IL1F10、IL1F5、IL1F6、IL1F7、IL1F8、IL1F9、IL22、IL5、IL−6、IL8、IL9、IL−18、IL−33、LTA、LTB、MIF、SCYE1、SPP1、TNF、CCL13(mcp−4)、CCR1、CCR2、CCR3、CCR4、CCR5、CCR6、CCR7、CCR8、CCR9、CX3CR1、IL8RA、XCR1(CCXCR1)、C5、CCL1(I−309)、CCL11(エオタキシン)、HMGB1、インターフェロンガンマ、IL−2、 IL−12、IL−17、IL33、 CCL13(mcp−4)(CCL15(MIP−1d)、CCL16(HCC−4)、CCL17(TARC)、CCL18(PARC)、CCL19、CCL2(mcp−1)、CCL20(MIP−3a)、補体成分C3とC5、2,3alpha gal、CCL21(MIP−2)、CCL23(MPIF−1)、CCL24(MPIF−2/エオタキシン−2)、CCL25(TECK)、CCL26、CCL3(MIP−1a)、CCL4(MIP−1b)、CCL5(RANTES)、CCL7(mcp−3)、CCL8(mcp−2)、CXCL1、CXCL10(IP−10)、CXCL11(I−TAC/IP−9)、CXCL12(SDF1)、CXCL13、CXCL14、CXCL2、CXCL3、CXCL5(ENA−78/LIX)、CXCL6(GCP−2)、CXCL9、IL13およびIL8を含む群から選択される。
本開示は以下の実施形態を含む。
[1]
中枢神経系における炎症性メディエーターの産生増加に関連する神経学的疾患を治療する方法であって、a)全身性炎症反応が増強している患者を同定するステップ、 b)前記全身性炎症反応を減少させるのに十分な濃度と頻度で希ガス含有組成物を投与するステップ、および、c)全身性の炎症反応の調節によって中枢神経系の炎症反応が減少するように、前記希ガス含有組成物の投与後の前記全身性炎症反応に基づいて前記希ガス含有組成の濃度または頻度を調整するステップを含んでいる、方法。
[2]
前記中枢神経系における炎症性メディエーターの産生増加に関連する前記神経学的疾患が、自閉症スペクトラム障害、広汎性発達障害、自閉症、レット症候群、小児期崩壊性障害、アスペルガー症候群および特定不能の広汎性発達障害(PDDNOS)、多発性硬化症、アルツハイマー病、パーキンソン病、筋萎縮性側索硬化症、外傷性脳損傷、慢性外傷性脳症、および脳卒中を含む群から選択される、[2]に記載の方法。
[3]
増強した前記全身性炎症反応は、免疫細胞を抽出することと、in vitroでの刺激されていないベースレベルにおいて、または、in vitroで前記免疫細胞に対してマイトジェン特性を備えている薬剤により刺激される活性化されたレベルにおいて、in vitroのサイトカイン産生を定量することとによって評価される、[1]に記載の方法。
[4]
前記炎症性サイトカインのレベルが、炎症性メディエーターの産生増加に関連する前記神経学的疾患に罹患していない患者における、年齢および性別を適合させた対照レベルと比較される、[3]に記載の方法。
[5]
前記炎症性サイトカインが、ABCF1、BCL6、C3、C4A、CEBPB、CRP、ICEBERG、IL1R1、IL1RN、IL8RB、LTB4R、TOLLIP、IFNA2、IL10RA、IL10RB、IL13、IL13RA1、IL5RA、IL9、IL9R、CD40LG(TNFSF5)、IFNA2、IL17C、IL1A、IL1B、IL1F10、IL1F5、IL1F6、IL1F7、IL1F8、IL1F9、IL22、IL5、IL−6、IL8、IL9、IL−18、IL−33、LTA、LTB、MIF、SCYE1、SPP1、TNF、CCL13(mcp−4)、CCR1、CCR2、CCR3、CCR4、CCR5、CCR6、CCR7、CCR8、CCR9、CX3CR1、IL8RA、XCR1(CCXCR1)、C5、CCL1(I−309)、CCL11(エオタキシン)、HMGB1、インターフェロンガンマ、IL−2、IL−12、IL−17、IL33、CCL13(mcp−4)、CCL15(MIP−1d)、CCL16(HCC−4)、CCL17(TARC)、CCL18(PARC)、CCL19、CCL2(mcp−1)、CCL20(MIP−3a)、補体成分C3とC5、2,3alpha gal、CCL21(MIP−2)、CCL23(MPIF−1)、CCL24(MPIF−2/エオタキシン−2)、CCL25(TECK)、CCL26、CCL3(MIP−1a)、CCL4(MIP−1b)、CCL5(RANTES)、CCL7(mcp−3)、CCL8(mcp−2)、CXCL1、CXCL10(IP−10)、CXCL11(I−TAC/IP−9)、CXCL12(SDF1)、CXCL13、CXCL14、CXCL2、CXCL3、CXCL5(ENA−78/LIX)、CXCL6(GCP−2)、CXCL9、IL13、およびIL8を含む群から選択される、[4]に記載の方法。
[6]
前記希ガス含有組成物が、キセノンおよび/またはキセノン供与体と、a)酸素、b)窒素、c)アルゴン、d)キセノン、e)ヘリウム、f)クリプトンおよびg)ネオンからなる群から選択される少なくとも1つのガス状成分とを含む、[1]に記載の方法。
[7]
前記希ガス含有混合物が、酸素および/または空気と、20〜70容量%の割合の希ガスとを含んでいるガス混合物を含む、[1]に記載の方法。
[8]
前記希ガスがキセノンである[7]に記載の方法。
[9]
前記炎症性サイトカイン関連の神経変性疾患が、25%キセノン―75%空気の混合物の投与によって改善され、前記混合物が炎症性サイトカインの産生を減少させるために必要な量に基づいて投与される、[1]に記載の方法。
[10]
前記空気が、実質的な麻酔効果なしに呼吸することを十分に許容する他のガス状混合物によって置換されている、[9]に記載の方法。
[11]
脳の炎症性メディエーターを減少させるのに十分な濃度と頻度で、麻酔域未満の濃度の一つ以上の希ガスを単独でまたは他のガスと組み合わせて投与することを含む、脳の炎症性メディエーターを減少させる方法。
[12]
前記炎症性メディエーターが、ABCF1、BCL6、C3、C4A、CEBPB、CRP、ICEBERG、IL1R1、IL1RN、IL8RB、LTB4R、TOLLIP、IFNA2、IL10RA、IL10RB、IL13、IL13RA1、IL5RA、IL9、IL9R、CD40LG(TNFSF5)、IFNA2、IL17C、IL1A、IL1B、IL1F10、IL1F5、IL1F6、IL1F7、IL1F8、IL1F9、IL22、IL5、IL−6、IL8、IL9、IL−18、IL−33、LTA、LTB、MIF、SCYE1、SPP1、TNF、CCL13(mcp−4)、CCR1、CCR2、CCR3、CCR4、CCR5、CCR6、CCR7、CCR8、CCR9、CX3CR1、IL8RA、XCR1(CCXCR1)、C5、CCL1(I−309)、CCL11(エオタキシン)、HMGB1、インターフェロンガンマ、IL−2、IL−12、IL−17、IL33、CCL13(mcp−4)、CCL15(MIP−1d)、CCL16(HCC−4)、CCL17(TARC)、CCL18(PARC)、CCL19、CCL2(mcp−1)、CCL20(MIP−3a)、補体成分C3およびC5、2,3 alpha gal、CCL21(MIP−2)、CCL23(MPIF−1)、CCL24(MPIF−2/エオタキシン−2)、CCL25(TECK)、CCL26、CCL3(MIP−1a)、CCL4(MIP−1b)、CCL5(RANTES)、CCL7(mcp−3)、CCL8(mcp−2)、CXCL1、CXCL10(IP−10)、CXCL11(I−TAC/IP−9)、CXCL12(SDF1)、CXCL13、CXCL14、CXCL2、CXCL3、CXCL5(ENA−78/LIX)、CXCL6(GCP−2)、CXCL9、IL13、およびIL8を含む群から選択される、[11]に記載の方法。
[13]
前記希ガスが、キセノン、ヘリウム、ネオン、アルゴン、およびクリプトンを含む群から選択される、[12]に記載の方法。
[14]
前記希ガスが、空気または酸素で希釈された15〜40%キセノンの形で投与される、[11]に記載の方法。
[15]
前記キセノンが、空気または酸素で希釈された25%の濃度で投与される、[14]に記載の方法。
[16]
前記キセノンが、1回の投与につき10リットルの体積において、1週間につき3回投与され、前記キセノンは、空気または酸素で希釈された25%キセノンの形で投与される、[11]に記載の方法。
[17]
自閉症患者に、空気または酸素で希釈された25%濃度のキセノン・ガスを投与することを含む、自閉症を治療する方法であって、前記投与は、1回の投与につき10リットルのガス体積において、一週間につき3回の投与で行われる、方法。
自閉症
小児自閉症
薬剤: キセノン/アルゴン/酸素吸入剤
試験のタイプ: 治療介入性
試験デザイン割り当て:無作為化
エンドポイント分類:安全性/有効性試験
治療介入モデル:単回群割り付け
マスキング:二重盲検法
主目的:治療
公式表題:小児自閉症におけるキセノン/アルゴン/酸素吸入剤対プラセボ
自閉症診断観察検査―包括的(ADOS−G)―ベースラインから最終来院時までの変化
臨床全般改善度(CGI)―ベースラインから最終来院時までの変化
異常行動チェックリスト(ABC)(多動/興奮性の項)―ベースラインから最終来院時までの変化
ヴァインランド適応行動尺度―ベースラインから最終来院時までの変化
マッカーサーコミュニケーション発達質問紙(MCDI)―ベースラインから最終来院時までの変化
コナーズ親・教師評価尺度改訂版: 長い形式(CPR−R:L)―ベースラインから最終来院時までの変化
試験に適格な年齢:5歳〜17歳
試験に適各な性別:男女両方
健康なボランティアを受け入れる:否
自閉症についてのDSM−IV、ADI−RおよびADOS−Gの基準を満たす
5歳〜17歳
外来患者
インフォームドコンセントに署名する意志のある親または法的保護者。
男性または女性の患者
Claims (13)
- 中枢神経系におけるTNF−alphaおよびIL−12からなる群から選択される炎症性メディエーターの産生増加に関連する神経学的疾患を治療する方法における使用のための希ガス含有組成物であって、前記方法は、a)前記炎症性メディエーターの産生増加を含む増強した全身性炎症反応をしている患者を同定するステップ、b)前記全身性炎症反応を減少させるのに十分な濃度と頻度で前記希ガス含有組成物を投与するステップ、および、c)全身性の炎症反応の調節によって中枢神経系の炎症反応が減少するように、前記希ガス含有組成物の投与後の前記全身性炎症反応に基づいて前記希ガス含有組成の濃度または頻度を調整するステップを含み、
前記患者の前記神経学的疾患は自閉症スペクトラム障害(ASD)であり、前記希ガスはキセノンである、
組成物。 - 前記自閉症スペクトラム障害(ASD)は、自閉症、レット症候群、小児期崩壊性障害、アスペルガー症候群および特定不能の広汎性発達障害(PDDNOS)を含む、請求項1に記載の組成物。
- 増強した前記全身性炎症反応は、免疫細胞を抽出することと、in vitroでの刺激されていないベースレベルにおいて、または、in vitroで前記免疫細胞に対してマイトジェン特性を備えている薬剤により刺激される活性化されたレベルにおいて、in vitroのサイトカイン産生を定量することとによって評価される、請求項1または2に記載の組成物。
- 前記サイトカインのレベルが、炎症性メディエーターの産生増加に関連する前記神経学的疾患に罹患していない患者における、年齢および性別を適合させた対照レベルと比較される、請求項3に記載の組成物。
- 前記希ガス含有組成物が、キセノンおよび/またはキセノン供与体と、a)酸素、b)窒素、c)アルゴン、d)キセノン、e)ヘリウム、f)クリプトンおよびg)ネオンからなる群から選択される少なくとも1つのガス状成分とを含む、請求項1〜4のいずれか一項に記載の組成物。
- 前記希ガス含有組成物が、酸素および/または空気と、20〜70容量%の割合の希ガスとを含んでいるガス混合物を含む、請求項1〜4のいずれか一項に記載の組成物。
- 25%キセノン―75%空気の混合物を含み、前記混合物が前記炎症性メディエーターの産生を減少させるために必要な量に基づいて投与される、請求項1〜4のいずれか一項に記載の組成物。
- 前記空気が、実質的な麻酔効果なしに呼吸することを十分に許容する他のガス状混合物によって置換されている、請求項7に記載の組成物。
- 脳のTNF−alphaおよびIL−12からなる群から選択される炎症性メディエーターを減少させるための組成物であって、前記組成物は、麻酔域未満の濃度の希ガスを単独でまたは他のガスと組み合わせて含み、前記希ガスが、脳の前記炎症性メディエーターを減少させるのに十分な濃度と頻度で対象に投与され、前記対象はアルツハイマー病もパーキンソン病も有さず、前記希ガスはキセノンである、組成物。
- 前記希ガスが、空気または酸素で希釈された15〜40%キセノンの形で投与される、請求項9に記載の組成物。
- 前記キセノンが、空気または酸素で希釈された25%の濃度で投与される、請求項10に記載の組成物。
- 前記組成物は、キセノンを含み、1回の投与につき10リットルの体積において、1週間につき3回投与され、前記キセノンは、空気または酸素で希釈された25%キセノンの形で投与される、請求項9に記載の組成物。
- TNF−alphaおよびIL−12からなる群から選択される炎症性メディエーターの産生増加に関連する自閉症を治療するための組成物であって、前記組成物は、空気または酸素で希釈された25%濃度のキセノン・ガスを含み、前記組成物は、1回の投与につき10リットルのガス体積において、一週間につき3回の投与で自閉症患者に投与される、組成物。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562183624P | 2015-06-23 | 2015-06-23 | |
US62/183,624 | 2015-06-23 | ||
US201662276753P | 2016-01-08 | 2016-01-08 | |
US62/276,753 | 2016-01-08 | ||
PCT/US2016/039038 WO2016210144A1 (en) | 2015-06-23 | 2016-06-23 | Therapeutic immune modulation using noble gas compositions |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2018518528A JP2018518528A (ja) | 2018-07-12 |
JP6622822B2 true JP6622822B2 (ja) | 2019-12-18 |
Family
ID=57586457
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017567439A Expired - Fee Related JP6622822B2 (ja) | 2015-06-23 | 2016-06-23 | 希ガス組成物を用いた治療的な免疫調節 |
Country Status (8)
Country | Link |
---|---|
US (1) | US10792305B2 (ja) |
EP (1) | EP3313384A4 (ja) |
JP (1) | JP6622822B2 (ja) |
CN (1) | CN107921008A (ja) |
AU (1) | AU2016281656B2 (ja) |
CA (1) | CA2989432C (ja) |
IL (1) | IL256490B (ja) |
WO (1) | WO2016210144A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109085359A (zh) * | 2017-06-13 | 2018-12-25 | 中国医学科学院肿瘤医院 | 血清蛋白标志物组合在结直肠癌筛查和诊治中的应用 |
EP3424490A1 (en) * | 2017-07-06 | 2019-01-09 | Monatomics Technology | Gas mixtures containing xenon and argon at low concentration as organ protectant, in particular neuroprotectant |
CN113163774A (zh) * | 2018-12-05 | 2021-07-23 | 马瑞奥肉品股份有限公司 | 一种降低动物应激水平的方法 |
JP7199656B2 (ja) * | 2018-12-07 | 2023-01-06 | 日本たばこ産業株式会社 | 注意欠如・多動症又は注意欠如・多動性障害の評価方法及び評価を補助するための方法、並びに注意欠如・多動症又は注意欠如・多動性障害を評価するためのデータ取得方法 |
US20230117859A1 (en) * | 2020-03-25 | 2023-04-20 | The Brigham And Women`S Hospital, Inc. | Inhaled xenon therapy in neurodegenerative disease |
CN117860892B (zh) * | 2023-12-26 | 2024-08-06 | 武汉大学中南医院 | Il-16阳性神经元在调节恐惧消退记忆中的作用 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19910986C2 (de) * | 1999-03-11 | 2001-06-07 | Aga Ab | Verwendung von Xenon bei der Behandlung von Neurointoxikationen |
US20050255169A1 (en) | 2002-07-05 | 2005-11-17 | Messer Griesheim | Adjuvant containing xenon |
BRPI0415232A (pt) | 2003-10-10 | 2006-12-12 | Protexeon Ltd | uso de xenÈnio com hipotermia para tratar asfixia neonatal |
EA014070B1 (ru) * | 2005-09-30 | 2010-08-30 | Пирамал Лайф Сайнсиз Лимитед | Применение растительной композиции для лечения воспалительных нарушений |
JP5332463B2 (ja) | 2008-09-30 | 2013-11-06 | セイコーエプソン株式会社 | Mems・半導体複合素子 |
US20130302445A1 (en) * | 2012-04-16 | 2013-11-14 | Denise Barbut | Apparatus and method for treating cerebral ischemia using non-inhaled carbon dioxide |
MX369290B (es) | 2012-06-08 | 2019-11-04 | Univ Of Pittsburgh Of The Commonwealth System Of Higher Education Star | Inhibidores de fbx03. |
CN110464709A (zh) * | 2012-08-10 | 2019-11-19 | 德克萨斯州大学系统董事会 | 用于治疗中风的神经保护性脂质体组合物和方法 |
PT2931291T (pt) * | 2012-12-11 | 2021-12-03 | Mclean Hospital Corp | Tratamento com xénon como complemento da psicoterapia para perturbações psiquiátricas |
US10555916B2 (en) * | 2013-01-25 | 2020-02-11 | Case Western Reserve University | NMDAR antagonist for the treatment of pervasive development disorders |
EP2968126B1 (en) * | 2013-03-15 | 2022-04-06 | The Board of Regents of The University of Texas System | Liquids rich in noble gas and methods of their preparation and use |
EP2968163A4 (en) * | 2013-03-15 | 2017-01-25 | Children's Medical Center Corporation | Hollow particles encapsulating a biological gas and methods of use |
WO2014145485A2 (en) | 2013-03-15 | 2014-09-18 | The Trustees Of Columbia University In The City Of New York | Map kinase modulators and uses thereof |
US20160039796A1 (en) | 2013-04-05 | 2016-02-11 | Abc Bioscience As | Barettin and derivatives thereof for medical use, in particular for the treatment of diseases related to oxidative stress or inflammation, and for preserving or washing organs |
FR3007983B1 (fr) | 2013-07-08 | 2015-06-26 | Air Liquide | Association de xenon et d'un antagoniste des recepteurs nmda pour lutter contre une maladie neurodegenerative |
FR3021220B1 (fr) * | 2014-05-21 | 2017-08-25 | Air Liquide | Association de xenon et d’un antioxydant pour lutter contre une maladie neurodegenerative de type maladie de parkinson |
-
2016
- 2016-06-23 WO PCT/US2016/039038 patent/WO2016210144A1/en active Application Filing
- 2016-06-23 US US15/738,025 patent/US10792305B2/en active Active
- 2016-06-23 EP EP16815312.0A patent/EP3313384A4/en not_active Withdrawn
- 2016-06-23 JP JP2017567439A patent/JP6622822B2/ja not_active Expired - Fee Related
- 2016-06-23 AU AU2016281656A patent/AU2016281656B2/en not_active Ceased
- 2016-06-23 CN CN201680047760.5A patent/CN107921008A/zh active Pending
- 2016-06-23 CA CA2989432A patent/CA2989432C/en active Active
-
2017
- 2017-12-21 IL IL256490A patent/IL256490B/en unknown
Also Published As
Publication number | Publication date |
---|---|
US10792305B2 (en) | 2020-10-06 |
IL256490A (en) | 2018-02-28 |
IL256490B (en) | 2021-12-01 |
US20180303871A1 (en) | 2018-10-25 |
AU2016281656B2 (en) | 2019-05-30 |
EP3313384A1 (en) | 2018-05-02 |
CN107921008A (zh) | 2018-04-17 |
WO2016210144A1 (en) | 2016-12-29 |
JP2018518528A (ja) | 2018-07-12 |
EP3313384A4 (en) | 2019-04-03 |
CA2989432C (en) | 2022-08-09 |
CA2989432A1 (en) | 2016-12-29 |
AU2016281656A1 (en) | 2017-12-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6622822B2 (ja) | 希ガス組成物を用いた治療的な免疫調節 | |
Yan et al. | Dysregulation of the adaptive immune system in patients with early-stage Parkinson disease | |
Himmerich et al. | Cytokine research in depression: principles, challenges, and open questions | |
Prajeeth et al. | Effectors of Th1 and Th17 cells act on astrocytes and augment their neuroinflammatory properties | |
Fan et al. | Altered serum levels of TNF‐α, IL‐6, and IL‐18 in depressive disorder patients | |
Hughes et al. | Stress-related immune markers in depression: implications for treatment | |
Amitai et al. | The relationship between plasma cytokine levels and response to selective serotonin reuptake inhibitor treatment in children and adolescents with depression and/or anxiety disorders | |
Kim et al. | Cytokine imbalance in the pathophysiology of major depressive disorder | |
Kordulewska et al. | Serum cytokine levels in children with spectrum autism disorder: Differences in pro-and anti-inflammatory balance | |
Al-Dujaili et al. | High mobility group protein 1 and dickkopf-related protein 1 in schizophrenia and treatment-resistant schizophrenia: Associations with interleukin-6, symptom domains, and neurocognitive impairments | |
Connors et al. | Lipid nanoparticles (LNP) induce activation and maturation of antigen presenting cells in young and aged individuals | |
Villegas et al. | Il-23/Th17 cell pathway: A promising target to alleviate thymic inflammation maintenance in myasthenia gravis | |
Babaloo et al. | Increased IL-17A but decreased IL-27 serum levels in patients with multiple sclerosis | |
Garfias et al. | Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson’s diseases | |
Rodriguez et al. | Altered frequencies of Th17 and Treg cells in children and adolescents with obsessive-compulsive disorder | |
Ahmad et al. | Upregulation of peripheral CXC and CC chemokine receptor expression on CD4+ T cells is associated with immune dysregulation in children with autism | |
Guo et al. | Inhibition of glial cell activation ameliorates the severity of experimental autoimmune encephalomyelitis | |
Corrigan et al. | Inflammation in the pathogenesis of depression: a disorder of neuroimmune origin | |
Saini et al. | Post-COVID-19 immune-mediated neurological complications in children: An ambispective study | |
Safavi et al. | Dimethyl fumarate suppresses granulocyte macrophage colony-stimulating factor–producing Th1 cells in CNS neuroinflammation | |
Makhlouf et al. | Oral salbutamol decreases IL-12 in patients with secondary progressive multiple sclerosis | |
Rubesa et al. | Immunological characteristics of schizophrenia | |
Liu et al. | Emerging roles of T helper cells in non-infectious neuroinflammation: savior or sinner | |
Kita et al. | Psychiatric adverse reaction to COVID-19 vaccine booster presenting as first-episode acute mania with psychotic features: A case report | |
Seyed Ebrahimi et al. | A review of the role of interleukin-2 in the pathophysiology of major depressive disorder in hospitalized patients |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180115 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180115 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180918 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181218 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190528 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190828 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191024 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20191112 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20191122 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6622822 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |