BRPI0617823A2 - uso de sdf-1 para o tratamento e/ou prevenção de doenças neurológicas e composição farmacêutica - Google Patents

Info

Publication number

BRPI0617823A2

BRPI0617823A2 BRPI0617823-5A BRPI0617823A BRPI0617823A2 BR PI0617823 A2 BRPI0617823 A2 BR PI0617823A2 BR PI0617823 A BRPI0617823 A BR PI0617823A BR PI0617823 A2 BRPI0617823 A2 BR PI0617823A2

Authority

BR

Brazil

Prior art keywords

sdf

use according

disease

treatment

amino acid

Prior art date

2005-10-31

Links

• Espacenet
• Global Dossier
• Discuss

• 238000011282 treatment Methods 0.000 title claims abstract description 59
• 208000012902 Nervous system disease Diseases 0.000 title claims abstract description 55
• 208000025966 Neurological disease Diseases 0.000 title claims abstract description 49
• 230000002265 prevention Effects 0.000 title claims abstract description 20
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
• 230000000694 effects Effects 0.000 claims abstract description 53
• 102100021669 Stromal cell-derived factor 1 Human genes 0.000 claims abstract description 44
• 239000000556 agonist Substances 0.000 claims abstract description 15
• 101710088580 Stromal cell-derived factor 1 Proteins 0.000 claims abstract 22
• 108090000623 proteins and genes Proteins 0.000 claims description 77
• 102000004169 proteins and genes Human genes 0.000 claims description 55
• 208000014674 injury Diseases 0.000 claims description 44
• 201000006417 multiple sclerosis Diseases 0.000 claims description 43
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 40
• 210000003169 central nervous system Anatomy 0.000 claims description 34
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 33
• 108010029485 Protein Isoforms Proteins 0.000 claims description 29
• 102000001708 Protein Isoforms Human genes 0.000 claims description 29
• 229920001184 polypeptide Polymers 0.000 claims description 29
• 150000001413 amino acids Chemical class 0.000 claims description 28
• 201000001119 neuropathy Diseases 0.000 claims description 28
• 230000007823 neuropathy Effects 0.000 claims description 28
• 208000033808 peripheral neuropathy Diseases 0.000 claims description 27
• 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 26
• 230000003959 neuroinflammation Effects 0.000 claims description 26
• 206010061218 Inflammation Diseases 0.000 claims description 25
• 230000004054 inflammatory process Effects 0.000 claims description 25
• 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 claims description 24
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 23
• 230000001684 chronic effect Effects 0.000 claims description 23
• 208000016192 Demyelinating disease Diseases 0.000 claims description 22
• 239000003814 drug Substances 0.000 claims description 21
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 19
• 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 19
• 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 19
• 210000000278 spinal cord Anatomy 0.000 claims description 19
• 230000002757 inflammatory effect Effects 0.000 claims description 17
• 238000004519 manufacturing process Methods 0.000 claims description 17
• 150000003839 salts Chemical class 0.000 claims description 17
• 230000037396 body weight Effects 0.000 claims description 16
• 150000007523 nucleic acids Chemical class 0.000 claims description 16
• 230000008733 trauma Effects 0.000 claims description 16
• 102000014150 Interferons Human genes 0.000 claims description 15
• 108010050904 Interferons Proteins 0.000 claims description 15
• 210000004369 blood Anatomy 0.000 claims description 15
• 239000008280 blood Substances 0.000 claims description 15
• 108091028043 Nucleic acid sequence Proteins 0.000 claims description 14
• 208000028389 Nerve injury Diseases 0.000 claims description 13
• 229940079322 interferon Drugs 0.000 claims description 13
• 230000008764 nerve damage Effects 0.000 claims description 13
• 108020004707 nucleic acids Proteins 0.000 claims description 12
• 102000039446 nucleic acids Human genes 0.000 claims description 12
• 208000006011 Stroke Diseases 0.000 claims description 11
• 208000007118 chronic progressive multiple sclerosis Diseases 0.000 claims description 11
• 206010063401 primary progressive multiple sclerosis Diseases 0.000 claims description 11
• 239000013598 vector Substances 0.000 claims description 11
• 230000002490 cerebral effect Effects 0.000 claims description 10
• 230000000472 traumatic effect Effects 0.000 claims description 10
• 238000006467 substitution reaction Methods 0.000 claims description 9
• 108090000467 Interferon-beta Proteins 0.000 claims description 8
• 108090000197 Clusterin Proteins 0.000 claims description 7
• 102000003780 Clusterin Human genes 0.000 claims description 7
• 102000004264 Osteopontin Human genes 0.000 claims description 7
• 108010081689 Osteopontin Proteins 0.000 claims description 7
• 230000000295 complement effect Effects 0.000 claims description 7
• 230000004888 barrier function Effects 0.000 claims description 6
• 229940079593 drug Drugs 0.000 claims description 6
• 239000013604 expression vector Substances 0.000 claims description 6
• 230000002093 peripheral effect Effects 0.000 claims description 6
• 201000008628 secondary progressive multiple sclerosis Diseases 0.000 claims description 6
• 108060003951 Immunoglobulin Proteins 0.000 claims description 5
• 102000003996 Interferon-beta Human genes 0.000 claims description 5
• 102000018358 immunoglobulin Human genes 0.000 claims description 5
• 208000004296 neuralgia Diseases 0.000 claims description 5
• 208000021722 neuropathic pain Diseases 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• 108010076504 Protein Sorting Signals Proteins 0.000 claims description 4
• 230000004927 fusion Effects 0.000 claims description 4
• 210000000578 peripheral nerve Anatomy 0.000 claims description 4
• 206010061811 demyelinating polyneuropathy Diseases 0.000 claims description 2
• 238000001415 gene therapy Methods 0.000 claims description 2
• 101000690100 Homo sapiens U1 small nuclear ribonucleoprotein 70 kDa Proteins 0.000 claims 1
• 102100024121 U1 small nuclear ribonucleoprotein 70 kDa Human genes 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 55
• 201000010099 disease Diseases 0.000 abstract description 34
• 230000000926 neurological effect Effects 0.000 abstract description 9
• 206010012601 diabetes mellitus Diseases 0.000 description 67
• 235000018102 proteins Nutrition 0.000 description 51
• 241000700159 Rattus Species 0.000 description 50
• 210000003205 muscle Anatomy 0.000 description 43
• 239000003981 vehicle Substances 0.000 description 42
• 210000004027 cell Anatomy 0.000 description 38
• 210000004556 brain Anatomy 0.000 description 36
• 108090001005 Interleukin-6 Proteins 0.000 description 34
• 102000004889 Interleukin-6 Human genes 0.000 description 34
• 230000006378 damage Effects 0.000 description 34
• 241000699670 Mus sp. Species 0.000 description 33
• 210000005036 nerve Anatomy 0.000 description 33
• 238000000034 method Methods 0.000 description 31
• 150000001875 compounds Chemical class 0.000 description 30
• 230000036982 action potential Effects 0.000 description 29
• 239000000835 fiber Substances 0.000 description 29
• 102000019034 Chemokines Human genes 0.000 description 26
• 108010012236 Chemokines Proteins 0.000 description 26
• 208000027418 Wounds and injury Diseases 0.000 description 26
• 235000001014 amino acid Nutrition 0.000 description 25
• 239000002158 endotoxin Substances 0.000 description 25
• 229920006008 lipopolysaccharide Polymers 0.000 description 25
• 238000012360 testing method Methods 0.000 description 25
• 241001465754 Metazoa Species 0.000 description 23
• 208000035475 disorder Diseases 0.000 description 21
• 206010029174 Nerve compression Diseases 0.000 description 20
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
• ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 20
• 230000027455 binding Effects 0.000 description 19
• 230000002829 reductive effect Effects 0.000 description 19
• 108010008951 Chemokine CXCL12 Proteins 0.000 description 18
• 102000006573 Chemokine CXCL12 Human genes 0.000 description 18
• 230000006870 function Effects 0.000 description 18
• 210000003497 sciatic nerve Anatomy 0.000 description 18
• 230000014509 gene expression Effects 0.000 description 17
• 230000000750 progressive effect Effects 0.000 description 16
• 229920002683 Glycosaminoglycan Polymers 0.000 description 15
• 230000001154 acute effect Effects 0.000 description 15
• 125000000539 amino acid group Chemical group 0.000 description 15
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 15
• 238000009739 binding Methods 0.000 description 15
• 230000004770 neurodegeneration Effects 0.000 description 15
• 210000001428 peripheral nervous system Anatomy 0.000 description 15
• 102000005962 receptors Human genes 0.000 description 15
• 108020003175 receptors Proteins 0.000 description 15
• 206010036105 Polyneuropathy Diseases 0.000 description 14
• 230000007824 polyneuropathy Effects 0.000 description 14
• 230000001953 sensory effect Effects 0.000 description 14
• 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 13
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 13
• 208000024891 symptom Diseases 0.000 description 13
• 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 12
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 12
• 238000004458 analytical method Methods 0.000 description 12
• 239000012634 fragment Substances 0.000 description 12
• 201000005518 mononeuropathy Diseases 0.000 description 12
• 208000015122 neurodegenerative disease Diseases 0.000 description 12
• 230000009467 reduction Effects 0.000 description 12
• 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 description 11
• 208000024827 Alzheimer disease Diseases 0.000 description 11
• 230000003902 lesion Effects 0.000 description 11
• 210000000265 leukocyte Anatomy 0.000 description 11
• 238000005259 measurement Methods 0.000 description 11
• 230000007830 nerve conduction Effects 0.000 description 11
• 239000011780 sodium chloride Substances 0.000 description 11
• 238000007920 subcutaneous administration Methods 0.000 description 11
• 230000007850 degeneration Effects 0.000 description 10
• 201000002491 encephalomyelitis Diseases 0.000 description 10
• 239000008103 glucose Substances 0.000 description 10
• 238000001727 in vivo Methods 0.000 description 10
• 208000015181 infectious disease Diseases 0.000 description 10
• 210000000274 microglia Anatomy 0.000 description 10
• 102000004127 Cytokines Human genes 0.000 description 9
• 108090000695 Cytokines Proteins 0.000 description 9
• 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 9
• 206010033799 Paralysis Diseases 0.000 description 9
• 208000018737 Parkinson disease Diseases 0.000 description 9
• 239000002202 Polyethylene glycol Substances 0.000 description 9
• 210000001130 astrocyte Anatomy 0.000 description 9
• 230000003376 axonal effect Effects 0.000 description 9
• 239000000872 buffer Substances 0.000 description 9
• 230000006835 compression Effects 0.000 description 9
• 238000007906 compression Methods 0.000 description 9
• 230000000875 corresponding effect Effects 0.000 description 9
• 230000001054 cortical effect Effects 0.000 description 9
• 210000004126 nerve fiber Anatomy 0.000 description 9
• 230000001537 neural effect Effects 0.000 description 9
• 210000002569 neuron Anatomy 0.000 description 9
• 229920001223 polyethylene glycol Polymers 0.000 description 9
• 230000001681 protective effect Effects 0.000 description 9
• LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 9
• 238000011084 recovery Methods 0.000 description 9
• 230000001105 regulatory effect Effects 0.000 description 9
• 238000002965 ELISA Methods 0.000 description 8
• ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 8
• 238000010171 animal model Methods 0.000 description 8
• 238000003556 assay Methods 0.000 description 8
• 230000004071 biological effect Effects 0.000 description 8
• 230000006698 induction Effects 0.000 description 8
• -1 pyridoxy Chemical group 0.000 description 8
• 230000007115 recruitment Effects 0.000 description 8
• 239000000243 solution Substances 0.000 description 8
• 229960001052 streptozocin Drugs 0.000 description 8
• 206010057645 Chronic Inflammatory Demyelinating Polyradiculoneuropathy Diseases 0.000 description 7
• 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 7
• 206010028980 Neoplasm Diseases 0.000 description 7
• 230000037444 atrophy Effects 0.000 description 7
• 230000017531 blood circulation Effects 0.000 description 7
• 230000002950 deficient Effects 0.000 description 7
• 230000003210 demyelinating effect Effects 0.000 description 7
• 238000011161 development Methods 0.000 description 7
• 230000002068 genetic effect Effects 0.000 description 7
• 230000001965 increasing effect Effects 0.000 description 7
• 208000027866 inflammatory disease Diseases 0.000 description 7
• 230000033001 locomotion Effects 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 239000012071 phase Substances 0.000 description 7
• 210000001519 tissue Anatomy 0.000 description 7
• 108010061299 CXCR4 Receptors Proteins 0.000 description 6
• 108020004414 DNA Proteins 0.000 description 6
• 208000023105 Huntington disease Diseases 0.000 description 6
• 108010083674 Myelin Proteins Proteins 0.000 description 6
• 102000006386 Myelin Proteins Human genes 0.000 description 6
• 208000002193 Pain Diseases 0.000 description 6
• 230000004913 activation Effects 0.000 description 6
• 201000011510 cancer Diseases 0.000 description 6
• 125000002091 cationic group Chemical group 0.000 description 6
• 230000018109 developmental process Effects 0.000 description 6
• 239000000203 mixture Substances 0.000 description 6
• 210000005012 myelin Anatomy 0.000 description 6
• 210000003007 myelin sheath Anatomy 0.000 description 6
• 230000023105 myelination Effects 0.000 description 6
• 210000004248 oligodendroglia Anatomy 0.000 description 6
• 230000008569 process Effects 0.000 description 6
• 230000009885 systemic effect Effects 0.000 description 6
• 206010003694 Atrophy Diseases 0.000 description 5
• 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 5
• 102000012000 CXCR4 Receptors Human genes 0.000 description 5
• 206010012289 Dementia Diseases 0.000 description 5
• 208000004454 Hyperalgesia Diseases 0.000 description 5
• 208000016604 Lyme disease Diseases 0.000 description 5
• 206010040030 Sensory loss Diseases 0.000 description 5
• 230000005856 abnormality Effects 0.000 description 5
• 125000000217 alkyl group Chemical group 0.000 description 5
• 210000005013 brain tissue Anatomy 0.000 description 5
• 230000004663 cell proliferation Effects 0.000 description 5
• 238000006243 chemical reaction Methods 0.000 description 5
• 238000007405 data analysis Methods 0.000 description 5
• 230000007812 deficiency Effects 0.000 description 5
• 238000012217 deletion Methods 0.000 description 5
• 230000037430 deletion Effects 0.000 description 5
• 210000002683 foot Anatomy 0.000 description 5
• 108020001507 fusion proteins Proteins 0.000 description 5
• 102000037865 fusion proteins Human genes 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 229930182817 methionine Natural products 0.000 description 5
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 5
• 230000035772 mutation Effects 0.000 description 5
• 210000000653 nervous system Anatomy 0.000 description 5
• 230000036407 pain Effects 0.000 description 5
• 239000002245 particle Substances 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 230000002035 prolonged effect Effects 0.000 description 5
• 230000035807 sensation Effects 0.000 description 5
• 230000000638 stimulation Effects 0.000 description 5
• 230000001225 therapeutic effect Effects 0.000 description 5
• 230000003612 virological effect Effects 0.000 description 5
• 229940011671 vitamin b6 Drugs 0.000 description 5
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 4
• 108700024394 Exon Proteins 0.000 description 4
• 206010019196 Head injury Diseases 0.000 description 4
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
• 201000009906 Meningitis Diseases 0.000 description 4
• 241000699666 Mus <mouse, genus> Species 0.000 description 4
• 208000036142 Viral infection Diseases 0.000 description 4
• 239000002253 acid Substances 0.000 description 4
• 230000001363 autoimmune Effects 0.000 description 4
• 210000003050 axon Anatomy 0.000 description 4
• 230000009286 beneficial effect Effects 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 210000001124 body fluid Anatomy 0.000 description 4
• 239000010839 body fluid Substances 0.000 description 4
• 208000029028 brain injury Diseases 0.000 description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
• 208000026106 cerebrovascular disease Diseases 0.000 description 4
• 230000034994 death Effects 0.000 description 4
• 230000007423 decrease Effects 0.000 description 4
• 230000003247 decreasing effect Effects 0.000 description 4
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 4
• 239000003937 drug carrier Substances 0.000 description 4
• 206010014599 encephalitis Diseases 0.000 description 4
• 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 4
• 238000002474 experimental method Methods 0.000 description 4
• 210000004884 grey matter Anatomy 0.000 description 4
• 230000001976 improved effect Effects 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 238000003780 insertion Methods 0.000 description 4
• 230000037431 insertion Effects 0.000 description 4
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
• 230000003993 interaction Effects 0.000 description 4
• 239000007928 intraperitoneal injection Substances 0.000 description 4
• 239000003446 ligand Substances 0.000 description 4
• 230000001404 mediated effect Effects 0.000 description 4
• 238000012544 monitoring process Methods 0.000 description 4
• 201000000585 muscular atrophy Diseases 0.000 description 4
• 230000007658 neurological function Effects 0.000 description 4
• 230000000324 neuroprotective effect Effects 0.000 description 4
• 230000006320 pegylation Effects 0.000 description 4
• 102000040430 polynucleotide Human genes 0.000 description 4
• 108091033319 polynucleotide Proteins 0.000 description 4
• 239000002157 polynucleotide Substances 0.000 description 4
• 239000002243 precursor Substances 0.000 description 4
• 230000035755 proliferation Effects 0.000 description 4
• 235000008160 pyridoxine Nutrition 0.000 description 4
• 239000011677 pyridoxine Substances 0.000 description 4
• 230000011514 reflex Effects 0.000 description 4
• 230000008929 regeneration Effects 0.000 description 4
• 238000011069 regeneration method Methods 0.000 description 4
• 230000028327 secretion Effects 0.000 description 4
• 210000002027 skeletal muscle Anatomy 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 238000001356 surgical procedure Methods 0.000 description 4
• 208000011580 syndromic disease Diseases 0.000 description 4
• 208000030507 AIDS Diseases 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 208000023275 Autoimmune disease Diseases 0.000 description 3
• 208000037157 Azotemia Diseases 0.000 description 3
• 208000035143 Bacterial infection Diseases 0.000 description 3
• 208000014644 Brain disease Diseases 0.000 description 3
• 101710082513 C-X-C chemokine receptor type 4 Proteins 0.000 description 3
• 206010012305 Demyelination Diseases 0.000 description 3
• 201000010374 Down Syndrome Diseases 0.000 description 3
• 208000032843 Hemorrhage Diseases 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
• 206010021143 Hypoxia Diseases 0.000 description 3
• 102100026720 Interferon beta Human genes 0.000 description 3
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
• 206010024229 Leprosy Diseases 0.000 description 3
• 206010028289 Muscle atrophy Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• 208000010886 Peripheral nerve injury Diseases 0.000 description 3
• 241000097929 Porphyria Species 0.000 description 3
• 208000010642 Porphyrias Diseases 0.000 description 3
• 108010067787 Proteoglycans Proteins 0.000 description 3
• 102000016611 Proteoglycans Human genes 0.000 description 3
• 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 3
• 210000001744 T-lymphocyte Anatomy 0.000 description 3
• 230000002159 abnormal effect Effects 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 3
• 238000013459 approach Methods 0.000 description 3
• 210000001367 artery Anatomy 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• 208000022362 bacterial infectious disease Diseases 0.000 description 3
• 230000006399 behavior Effects 0.000 description 3
• 230000036770 blood supply Effects 0.000 description 3
• 230000003925 brain function Effects 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• 239000002975 chemoattractant Substances 0.000 description 3
• 238000002512 chemotherapy Methods 0.000 description 3
• 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 3
• 230000006866 deterioration Effects 0.000 description 3
• 229960003957 dexamethasone Drugs 0.000 description 3
• 206010013023 diphtheria Diseases 0.000 description 3
• 230000004064 dysfunction Effects 0.000 description 3
• 235000013305 food Nutrition 0.000 description 3
• 230000005021 gait Effects 0.000 description 3
• 230000012010 growth Effects 0.000 description 3
• 210000000548 hind-foot Anatomy 0.000 description 3
• 229910052739 hydrogen Inorganic materials 0.000 description 3
• 239000001257 hydrogen Substances 0.000 description 3
• 230000007954 hypoxia Effects 0.000 description 3
• 239000003018 immunosuppressive agent Substances 0.000 description 3
• 238000007918 intramuscular administration Methods 0.000 description 3
• 208000028867 ischemia Diseases 0.000 description 3
• 210000004379 membrane Anatomy 0.000 description 3
• 208000030159 metabolic disease Diseases 0.000 description 3
• 238000007491 morphometric analysis Methods 0.000 description 3
• 210000004498 neuroglial cell Anatomy 0.000 description 3
• 230000007971 neurological deficit Effects 0.000 description 3
• 238000001543 one-way ANOVA Methods 0.000 description 3
• 229910052760 oxygen Inorganic materials 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• 230000007170 pathology Effects 0.000 description 3
• 238000011458 pharmacological treatment Methods 0.000 description 3
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
• 239000010452 phosphate Substances 0.000 description 3
• 208000000813 polyradiculoneuropathy Diseases 0.000 description 3
• 230000004850 protein–protein interaction Effects 0.000 description 3
• 150000003254 radicals Chemical class 0.000 description 3
• 230000000306 recurrent effect Effects 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 210000004116 schwann cell Anatomy 0.000 description 3
• 210000000273 spinal nerve root Anatomy 0.000 description 3
• 230000004936 stimulating effect Effects 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• 210000002435 tendon Anatomy 0.000 description 3
• 229940124597 therapeutic agent Drugs 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 230000002588 toxic effect Effects 0.000 description 3
• 230000001988 toxicity Effects 0.000 description 3
• 231100000419 toxicity Toxicity 0.000 description 3
• 208000009852 uremia Diseases 0.000 description 3
• 238000002255 vaccination Methods 0.000 description 3
• 230000009385 viral infection Effects 0.000 description 3
• GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
• FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
• 108700028369 Alleles Proteins 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• 101100424823 Arabidopsis thaliana TDT gene Proteins 0.000 description 2
• 206010003497 Asphyxia Diseases 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 208000024806 Brain atrophy Diseases 0.000 description 2
• 125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
• 102000001902 CC Chemokines Human genes 0.000 description 2
• 108010040471 CC Chemokines Proteins 0.000 description 2
• 208000014912 Central Nervous System Infections Diseases 0.000 description 2
• 102000008186 Collagen Human genes 0.000 description 2
• 108010035532 Collagen Proteins 0.000 description 2
• 206010010071 Coma Diseases 0.000 description 2
• 208000034656 Contusions Diseases 0.000 description 2
• 206010061818 Disease progression Diseases 0.000 description 2
• 238000001061 Dunnett's test Methods 0.000 description 2
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
• WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
• 229920002971 Heparan sulfate Polymers 0.000 description 2
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• 102000004877 Insulin Human genes 0.000 description 2
• 108090001061 Insulin Proteins 0.000 description 2
• 102100040019 Interferon alpha-1/13 Human genes 0.000 description 2
• 108090000174 Interleukin-10 Proteins 0.000 description 2
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• 208000002720 Malnutrition Diseases 0.000 description 2
• 241001529936 Murinae Species 0.000 description 2
• 208000010428 Muscle Weakness Diseases 0.000 description 2
• 206010028372 Muscular weakness Diseases 0.000 description 2
• 102100023302 Myelin-oligodendrocyte glycoprotein Human genes 0.000 description 2
• OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 2
• 206010033892 Paraplegia Diseases 0.000 description 2
• 206010034620 Peripheral sensory neuropathy Diseases 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• 208000029033 Spinal Cord disease Diseases 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 208000007536 Thrombosis Diseases 0.000 description 2
• RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
• 208000030886 Traumatic Brain injury Diseases 0.000 description 2
• 102100040247 Tumor necrosis factor Human genes 0.000 description 2
• 229940122803 Vinca alkaloid Drugs 0.000 description 2
• 241000700605 Viruses Species 0.000 description 2
• 206010073696 Wallerian degeneration Diseases 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 210000001642 activated microglia Anatomy 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 208000002552 acute disseminated encephalomyelitis Diseases 0.000 description 2
• 125000002252 acyl group Chemical group 0.000 description 2
• 238000001042 affinity chromatography Methods 0.000 description 2
• 206010002022 amyloidosis Diseases 0.000 description 2
• 238000000540 analysis of variance Methods 0.000 description 2
• 125000000129 anionic group Chemical group 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 230000006907 apoptotic process Effects 0.000 description 2
• 230000001580 bacterial effect Effects 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 238000011953 bioanalysis Methods 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 230000000740 bleeding effect Effects 0.000 description 2
• 230000036760 body temperature Effects 0.000 description 2
• 230000006931 brain damage Effects 0.000 description 2
• 231100000874 brain damage Toxicity 0.000 description 2
• 239000008366 buffered solution Substances 0.000 description 2
• 210000004899 c-terminal region Anatomy 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 230000003915 cell function Effects 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 208000025222 central nervous system infectious disease Diseases 0.000 description 2
• 210000004720 cerebrum Anatomy 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 210000000349 chromosome Anatomy 0.000 description 2
• 238000010367 cloning Methods 0.000 description 2
• 229920001436 collagen Polymers 0.000 description 2
• 239000002131 composite material Substances 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 210000003792 cranial nerve Anatomy 0.000 description 2
• 230000006837 decompression Effects 0.000 description 2
• 230000006735 deficit Effects 0.000 description 2
• 230000003412 degenerative effect Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 239000003599 detergent Substances 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 230000005750 disease progression Effects 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• 238000002567 electromyography Methods 0.000 description 2
• 230000003511 endothelial effect Effects 0.000 description 2
• 210000002744 extracellular matrix Anatomy 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 238000013467 fragmentation Methods 0.000 description 2
• 238000006062 fragmentation reaction Methods 0.000 description 2
• 238000001502 gel electrophoresis Methods 0.000 description 2
• 238000012120 genotypic test Methods 0.000 description 2
• KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
• 229910052736 halogen Inorganic materials 0.000 description 2
• 150000002367 halogens Chemical class 0.000 description 2
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
• 230000002008 hemorrhagic effect Effects 0.000 description 2
• 102000043525 human CXCL12 Human genes 0.000 description 2
• 201000001421 hyperglycemia Diseases 0.000 description 2
• 208000034783 hypoesthesia Diseases 0.000 description 2
• 230000005847 immunogenicity Effects 0.000 description 2
• 229940125721 immunosuppressive agent Drugs 0.000 description 2
• 238000009169 immunotherapy Methods 0.000 description 2
• 238000011419 induction treatment Methods 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 229940125396 insulin Drugs 0.000 description 2
• 229940047124 interferons Drugs 0.000 description 2
• 238000010255 intramuscular injection Methods 0.000 description 2
• 239000007927 intramuscular injection Substances 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 238000010253 intravenous injection Methods 0.000 description 2
• 230000009545 invasion Effects 0.000 description 2
• 238000011835 investigation Methods 0.000 description 2
• 229960003350 isoniazid Drugs 0.000 description 2
• QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 2
• 208000036546 leukodystrophy Diseases 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 230000007774 longterm Effects 0.000 description 2
• 210000002540 macrophage Anatomy 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• 210000002418 meninge Anatomy 0.000 description 2
• 230000003340 mental effect Effects 0.000 description 2
• 230000002025 microglial effect Effects 0.000 description 2
• 230000005012 migration Effects 0.000 description 2
• 238000013508 migration Methods 0.000 description 2
• 238000010172 mouse model Methods 0.000 description 2
• 230000007383 nerve stimulation Effects 0.000 description 2
• 230000002981 neuropathic effect Effects 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000002773 nucleotide Substances 0.000 description 2
• 125000003729 nucleotide group Chemical group 0.000 description 2
• 231100000862 numbness Toxicity 0.000 description 2
• 235000018343 nutrient deficiency Nutrition 0.000 description 2
• 230000003565 oculomotor Effects 0.000 description 2
• 238000006384 oligomerization reaction Methods 0.000 description 2
• 239000002751 oligonucleotide probe Substances 0.000 description 2
• 208000035824 paresthesia Diseases 0.000 description 2
• 208000027232 peripheral nervous system disease Diseases 0.000 description 2
• 210000003200 peritoneal cavity Anatomy 0.000 description 2
• 102000013415 peroxidase activity proteins Human genes 0.000 description 2
• 108040007629 peroxidase activity proteins Proteins 0.000 description 2
• 230000002085 persistent effect Effects 0.000 description 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
• 239000008055 phosphate buffer solution Substances 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 239000013641 positive control Substances 0.000 description 2
• 230000008092 positive effect Effects 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 238000002360 preparation method Methods 0.000 description 2
• 230000000770 proinflammatory effect Effects 0.000 description 2
• 230000000272 proprioceptive effect Effects 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 238000011002 quantification Methods 0.000 description 2
• 239000000018 receptor agonist Substances 0.000 description 2
• 229940044601 receptor agonist Drugs 0.000 description 2
• 230000002336 repolarization Effects 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 230000000717 retained effect Effects 0.000 description 2
• 201000000306 sarcoidosis Diseases 0.000 description 2
• 201000005572 sensory peripheral neuropathy Diseases 0.000 description 2
• 238000007390 skin biopsy Methods 0.000 description 2
• 210000003625 skull Anatomy 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 208000020431 spinal cord injury Diseases 0.000 description 2
• 210000003594 spinal ganglia Anatomy 0.000 description 2
• 238000013222 sprague-dawley male rat Methods 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium group Chemical group [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 2
• 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000010936 titanium Substances 0.000 description 2
• 229910052719 titanium Inorganic materials 0.000 description 2
• 231100000331 toxic Toxicity 0.000 description 2
• 231100000167 toxic agent Toxicity 0.000 description 2
• 239000003440 toxic substance Substances 0.000 description 2
• 230000008736 traumatic injury Effects 0.000 description 2
• 230000001457 vasomotor Effects 0.000 description 2
• 239000011782 vitamin Substances 0.000 description 2
• 229940088594 vitamin Drugs 0.000 description 2
• 235000013343 vitamin Nutrition 0.000 description 2
• 229930003231 vitamin Natural products 0.000 description 2
• 230000008734 wallerian degeneration Effects 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 210000004885 white matter Anatomy 0.000 description 2
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
• NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
• VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 description 1
• YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
• 229940124321 AIDS medicine Drugs 0.000 description 1
• 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 1
• 208000007848 Alcoholism Diseases 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 206010003399 Arthropod bite Diseases 0.000 description 1
• FBODFHMLALOPHP-GUBZILKMSA-N Asn-Lys-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O FBODFHMLALOPHP-GUBZILKMSA-N 0.000 description 1
• XAJRHVUUVUPFQL-ACZMJKKPSA-N Asp-Glu-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XAJRHVUUVUPFQL-ACZMJKKPSA-N 0.000 description 1
• 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
• 108090001008 Avidin Proteins 0.000 description 1
• 208000000412 Avitaminosis Diseases 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 206010061728 Bone lesion Diseases 0.000 description 1
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 101001027327 Bos taurus Growth-regulated protein homolog alpha Proteins 0.000 description 1
• 102400000967 Bradykinin Human genes 0.000 description 1
• 101800004538 Bradykinin Proteins 0.000 description 1
• 208000002381 Brain Hypoxia Diseases 0.000 description 1
• 201000006474 Brain Ischemia Diseases 0.000 description 1
• 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 1
• 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
• 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
• 108010075254 C-Peptide Proteins 0.000 description 1
• 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 1
• 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 1
• 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 1
• 102100037084 C4b-binding protein alpha chain Human genes 0.000 description 1
• 238000011749 CBA mouse Methods 0.000 description 1
• 108050006947 CXC Chemokine Proteins 0.000 description 1
• 102000019388 CXC chemokine Human genes 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 108010078791 Carrier Proteins Proteins 0.000 description 1
• 206010008025 Cerebellar ataxia Diseases 0.000 description 1
• 206010008096 Cerebral atrophy Diseases 0.000 description 1
• 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
• 206010008132 Cerebral thrombosis Diseases 0.000 description 1
• 206010008190 Cerebrovascular accident Diseases 0.000 description 1
• 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 description 1
• 201000006868 Charcot-Marie-Tooth disease type 3 Diseases 0.000 description 1
• 102000016950 Chemokine CXCL1 Human genes 0.000 description 1
• 102000009410 Chemokine receptor Human genes 0.000 description 1
• 108050000299 Chemokine receptor Proteins 0.000 description 1
• GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 108020004705 Codon Proteins 0.000 description 1
• 208000035473 Communicable disease Diseases 0.000 description 1
• 108020004635 Complementary DNA Proteins 0.000 description 1
• 206010010904 Convulsion Diseases 0.000 description 1
• 241000709687 Coxsackievirus Species 0.000 description 1
• 208000019736 Cranial nerve disease Diseases 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 101710163092 D-lysergyl-peptide-synthetase subunit 1 Proteins 0.000 description 1
• 102000053602 DNA Human genes 0.000 description 1
• 102000012410 DNA Ligases Human genes 0.000 description 1
• 108010061982 DNA Ligases Proteins 0.000 description 1
• 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
• 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 1
• 102220605444 DNA-(apurinic or apyrimidinic site) endonuclease_K24A_mutation Human genes 0.000 description 1
• MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 description 1
• 206010012218 Delirium Diseases 0.000 description 1
• 229920004937 Dexon® Polymers 0.000 description 1
• 208000002249 Diabetes Complications Diseases 0.000 description 1
• 206010012655 Diabetic complications Diseases 0.000 description 1
• 206010012735 Diarrhoea Diseases 0.000 description 1
• BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 1
• 208000000202 Diffuse Axonal Injury Diseases 0.000 description 1
• 208000012661 Dyskinesia Diseases 0.000 description 1
• 241001466953 Echovirus Species 0.000 description 1
• 241000709661 Enterovirus Species 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 102100029951 Estrogen receptor beta Human genes 0.000 description 1
• 206010015769 Extradural haematoma Diseases 0.000 description 1
• 208000034347 Faecal incontinence Diseases 0.000 description 1
• 102000009109 Fc receptors Human genes 0.000 description 1
• 108010087819 Fc receptors Proteins 0.000 description 1
• 108091006020 Fc-tagged proteins Proteins 0.000 description 1
• 208000001836 Firesetting Behavior Diseases 0.000 description 1
• 102100020997 Fractalkine Human genes 0.000 description 1
• 108091006027 G proteins Proteins 0.000 description 1
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
• 102000030782 GTP binding Human genes 0.000 description 1
• 108091000058 GTP-Binding Proteins 0.000 description 1
• 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
• TWHDOEYLXXQYOZ-FXQIFTODSA-N Gln-Asn-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N TWHDOEYLXXQYOZ-FXQIFTODSA-N 0.000 description 1
• OWOFCNWTMWOOJJ-WDSKDSINSA-N Gln-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O OWOFCNWTMWOOJJ-WDSKDSINSA-N 0.000 description 1
• XEKAJTCACGEBOK-KKUMJFAQSA-N Glu-Met-Phe Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N XEKAJTCACGEBOK-KKUMJFAQSA-N 0.000 description 1
• CHDWDBPJOZVZSE-KKUMJFAQSA-N Glu-Phe-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(O)=O CHDWDBPJOZVZSE-KKUMJFAQSA-N 0.000 description 1
• SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
• 102100034221 Growth-regulated alpha protein Human genes 0.000 description 1
• QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 208000037357 HIV infectious disease Diseases 0.000 description 1
• 206010018985 Haemorrhage intracranial Diseases 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
• 208000006411 Hereditary Sensory and Motor Neuropathy Diseases 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 102000009331 Homeodomain Proteins Human genes 0.000 description 1
• 108010048671 Homeodomain Proteins Proteins 0.000 description 1
• 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 1
• 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 1
• 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 1
• 101000740689 Homo sapiens C4b-binding protein beta chain Proteins 0.000 description 1
• 101000980898 Homo sapiens Cell division cycle-associated protein 4 Proteins 0.000 description 1
• 101000854520 Homo sapiens Fractalkine Proteins 0.000 description 1
• 101001069921 Homo sapiens Growth-regulated alpha protein Proteins 0.000 description 1
• 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
• 208000035154 Hyperesthesia Diseases 0.000 description 1
• 208000004044 Hypesthesia Diseases 0.000 description 1
• 206010021135 Hypovitaminosis Diseases 0.000 description 1
• 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
• 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
• 206010062016 Immunosuppression Diseases 0.000 description 1
• 206010061216 Infarction Diseases 0.000 description 1
• 102100037850 Interferon gamma Human genes 0.000 description 1
• 108010074328 Interferon-gamma Proteins 0.000 description 1
• 108010002352 Interleukin-1 Proteins 0.000 description 1
• 208000008574 Intracranial Hemorrhages Diseases 0.000 description 1
• 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
• 208000027747 Kennedy disease Diseases 0.000 description 1
• 102000011782 Keratins Human genes 0.000 description 1
• 108010076876 Keratins Proteins 0.000 description 1
• WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
• WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• 208000034693 Laceration Diseases 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• OVIVOCSURJYCTM-GUBZILKMSA-N Lys-Asp-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(O)=O OVIVOCSURJYCTM-GUBZILKMSA-N 0.000 description 1
• 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
• UYDDNEYNGGSTDW-OYDLWJJNSA-N Met-Trp-Trp Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)O)N UYDDNEYNGGSTDW-OYDLWJJNSA-N 0.000 description 1
• 208000016285 Movement disease Diseases 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 101001033265 Mus musculus Interleukin-10 Proteins 0.000 description 1
• 101000617124 Mus musculus Stromal cell-derived factor 1 Proteins 0.000 description 1
• 208000007101 Muscle Cramp Diseases 0.000 description 1
• OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
• 238000011785 NMRI mouse Methods 0.000 description 1
• 208000006079 Near drowning Diseases 0.000 description 1
• 206010028851 Necrosis Diseases 0.000 description 1
• 208000001738 Nervous System Trauma Diseases 0.000 description 1
• 208000009905 Neurofibromatoses Diseases 0.000 description 1
• 206010060860 Neurological symptom Diseases 0.000 description 1
• 206010029350 Neurotoxicity Diseases 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
• 108700026244 Open Reading Frames Proteins 0.000 description 1
• 206010031127 Orthostatic hypotension Diseases 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 206010031252 Osteomyelitis Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 229930012538 Paclitaxel Natural products 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 238000001358 Pearson's chi-squared test Methods 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 208000031845 Pernicious anaemia Diseases 0.000 description 1
• 206010057249 Phagocytosis Diseases 0.000 description 1
• CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 208000005374 Poisoning Diseases 0.000 description 1
• 102000029797 Prion Human genes 0.000 description 1
• 108091000054 Prion Proteins 0.000 description 1
• 208000024777 Prion disease Diseases 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• 206010037714 Quadriplegia Diseases 0.000 description 1
• 101150023114 RNA1 gene Proteins 0.000 description 1
• 108020004511 Recombinant DNA Proteins 0.000 description 1
• 208000001647 Renal Insufficiency Diseases 0.000 description 1
• 206010039203 Road traffic accident Diseases 0.000 description 1
• AUVVAXYIELKVAI-UHFFFAOYSA-N SJ000285215 Natural products N1CCC2=CC(OC)=C(OC)C=C2C1CC1CC2C3=CC(OC)=C(OC)C=C3CCN2CC1CC AUVVAXYIELKVAI-UHFFFAOYSA-N 0.000 description 1
• 206010039670 Sciatic nerve injury Diseases 0.000 description 1
• 206010039966 Senile dementia Diseases 0.000 description 1
• 206010040021 Sensory abnormalities Diseases 0.000 description 1
• 102000007562 Serum Albumin Human genes 0.000 description 1
• 108010071390 Serum Albumin Proteins 0.000 description 1
• 208000021386 Sjogren Syndrome Diseases 0.000 description 1
• 208000020339 Spinal injury Diseases 0.000 description 1
• 208000010513 Stupor Diseases 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 108010006785 Taq Polymerase Proteins 0.000 description 1
• 229940123237 Taxane Drugs 0.000 description 1
• 102220537443 Testin_K25A_mutation Human genes 0.000 description 1
• 102220537421 Testin_K27A_mutation Human genes 0.000 description 1
• JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
• 102220484179 Thioredoxin domain-containing protein 8_K28A_mutation Human genes 0.000 description 1
• 208000004374 Tick Bites Diseases 0.000 description 1
• 206010044221 Toxic encephalopathy Diseases 0.000 description 1
• 102000004338 Transferrin Human genes 0.000 description 1
• 108090000901 Transferrin Proteins 0.000 description 1
• 108010033576 Transferrin Receptors Proteins 0.000 description 1
• 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
• 206010044565 Tremor Diseases 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 206010044688 Trisomy 21 Diseases 0.000 description 1
• 102000004142 Trypsin Human genes 0.000 description 1
• 108090000631 Trypsin Proteins 0.000 description 1
• 208000025865 Ulcer Diseases 0.000 description 1
• 208000003443 Unconsciousness Diseases 0.000 description 1
• 206010046543 Urinary incontinence Diseases 0.000 description 1
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
• 206010047601 Vitamin B1 deficiency Diseases 0.000 description 1
• 206010047700 Vomiting Diseases 0.000 description 1
• 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 1
• WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 1
• 102220477041 Zinc fingers and homeoboxes protein 1, isoform 2_H25A_mutation Human genes 0.000 description 1
• 102220477042 Zinc fingers and homeoboxes protein 1, isoform 2_H26A_mutation Human genes 0.000 description 1
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
• CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
• 210000001015 abdomen Anatomy 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 210000001361 achilles tendon Anatomy 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 208000038016 acute inflammation Diseases 0.000 description 1
• 230000006022 acute inflammation Effects 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 238000001261 affinity purification Methods 0.000 description 1
• 201000007930 alcohol dependence Diseases 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 206010053552 allodynia Diseases 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 230000006229 amino acid addition Effects 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 150000001449 anionic compounds Chemical class 0.000 description 1
• 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
• 238000011861 anti-inflammatory therapy Methods 0.000 description 1
• 230000030741 antigen processing and presentation Effects 0.000 description 1
• 230000000890 antigenic effect Effects 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 125000003435 aroyl group Chemical group 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 239000005667 attractant Substances 0.000 description 1
• 230000006470 autoimmune attack Effects 0.000 description 1
• 210000003403 autonomic nervous system Anatomy 0.000 description 1
• 230000007844 axonal damage Effects 0.000 description 1
• 230000007845 axonopathy Effects 0.000 description 1
• 229960002319 barbital Drugs 0.000 description 1
• 238000002869 basic local alignment search tool Methods 0.000 description 1
• 230000003542 behavioural effect Effects 0.000 description 1
• 208000002894 beriberi Diseases 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 229960003237 betaine Drugs 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 239000013060 biological fluid Substances 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 210000001218 blood-brain barrier Anatomy 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
• 210000004958 brain cell Anatomy 0.000 description 1
• 230000001612 cachectic effect Effects 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 125000001589 carboacyl group Chemical group 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 210000001715 carotid artery Anatomy 0.000 description 1
• 208000003295 carpal tunnel syndrome Diseases 0.000 description 1
• 230000020411 cell activation Effects 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 238000001516 cell proliferation assay Methods 0.000 description 1
• 230000006041 cell recruitment Effects 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 230000003833 cell viability Effects 0.000 description 1
• 230000005754 cellular signaling Effects 0.000 description 1
• 230000021617 central nervous system development Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 230000031902 chemoattractant activity Effects 0.000 description 1
• 230000003399 chemotactic effect Effects 0.000 description 1
• 229940044683 chemotherapy drug Drugs 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 230000001713 cholinergic effect Effects 0.000 description 1
• 210000002932 cholinergic neuron Anatomy 0.000 description 1
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• 239000007979 citrate buffer Substances 0.000 description 1
• 238000000749 co-immunoprecipitation Methods 0.000 description 1
• 230000008045 co-localization Effects 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 230000006999 cognitive decline Effects 0.000 description 1
• 208000010877 cognitive disease Diseases 0.000 description 1
• 230000024203 complement activation Effects 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 230000021615 conjugation Effects 0.000 description 1
• 230000036461 convulsion Effects 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 229910052593 corundum Inorganic materials 0.000 description 1
• 229940121384 cxc chemokine receptor type 4 (cxcr4) antagonist Drugs 0.000 description 1
• 230000001351 cycling effect Effects 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 229960000860 dapsone Drugs 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 238000004925 denaturation Methods 0.000 description 1
• 230000036425 denaturation Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 238000013400 design of experiment Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 201000002342 diabetic polyneuropathy Diseases 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 229960002656 didanosine Drugs 0.000 description 1
• 230000009521 diffuse axonal injury Effects 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• 230000003292 diminished effect Effects 0.000 description 1
• 238000002845 discoloration Methods 0.000 description 1
• 230000009266 disease activity Effects 0.000 description 1
• 230000009429 distress Effects 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 238000002651 drug therapy Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 230000002500 effect on skin Effects 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 210000002257 embryonic structure Anatomy 0.000 description 1
• AUVVAXYIELKVAI-CKBKHPSWSA-N emetine Chemical compound N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@@H]1CC AUVVAXYIELKVAI-CKBKHPSWSA-N 0.000 description 1
• 229960002694 emetine Drugs 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
• 239000003797 essential amino acid Substances 0.000 description 1
• 235000020776 essential amino acid Nutrition 0.000 description 1
• 201000010934 exostosis Diseases 0.000 description 1
• 210000003414 extremity Anatomy 0.000 description 1
• 239000004744 fabric Substances 0.000 description 1
• 238000007667 floating Methods 0.000 description 1
• 238000002795 fluorescence method Methods 0.000 description 1
• 229960000304 folic acid Drugs 0.000 description 1
• 235000019152 folic acid Nutrition 0.000 description 1
• 239000011724 folic acid Substances 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 238000010413 gardening Methods 0.000 description 1
• 238000002523 gelfiltration Methods 0.000 description 1
• 238000003205 genotyping method Methods 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 125000003827 glycol group Chemical group 0.000 description 1
• 210000003714 granulocyte Anatomy 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 229910001385 heavy metal Inorganic materials 0.000 description 1
• 210000000777 hematopoietic system Anatomy 0.000 description 1
• 230000002439 hemostatic effect Effects 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• UYXAWHWODHRRMR-UHFFFAOYSA-N hexobarbital Chemical compound O=C1N(C)C(=O)NC(=O)C1(C)C1=CCCCC1 UYXAWHWODHRRMR-UHFFFAOYSA-N 0.000 description 1
• 229960002456 hexobarbital Drugs 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 238000000265 homogenisation Methods 0.000 description 1
• 238000002744 homologous recombination Methods 0.000 description 1
• 230000006801 homologous recombination Effects 0.000 description 1
• 102000044493 human CDCA4 Human genes 0.000 description 1
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
• 238000009396 hybridization Methods 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
• 201000010930 hyperostosis Diseases 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• 208000003532 hypothyroidism Diseases 0.000 description 1
• 230000002989 hypothyroidism Effects 0.000 description 1
• 230000009524 hypoxic brain injury Effects 0.000 description 1
• 210000002865 immune cell Anatomy 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 230000008105 immune reaction Effects 0.000 description 1
• 230000037451 immune surveillance Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000003053 immunization Effects 0.000 description 1
• 238000002649 immunization Methods 0.000 description 1
• 230000002163 immunogen Effects 0.000 description 1
• 230000001506 immunosuppresive effect Effects 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 230000001861 immunosuppressant effect Effects 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 201000001881 impotence Diseases 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000010874 in vitro model Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 230000007574 infarction Effects 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 210000004969 inflammatory cell Anatomy 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229910001412 inorganic anion Inorganic materials 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 229960001388 interferon-beta Drugs 0.000 description 1
• 230000035987 intoxication Effects 0.000 description 1
• 231100000566 intoxication Toxicity 0.000 description 1
• 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 230000002427 irreversible effect Effects 0.000 description 1
• 230000000302 ischemic effect Effects 0.000 description 1
• 201000006370 kidney failure Diseases 0.000 description 1
• 230000002045 lasting effect Effects 0.000 description 1
• 231100000518 lethal Toxicity 0.000 description 1
• 230000001665 lethal effect Effects 0.000 description 1
• 125000005647 linker group Chemical group 0.000 description 1
• 230000005923 long-lasting effect Effects 0.000 description 1
• 210000003141 lower extremity Anatomy 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
• 239000004137 magnesium phosphate Substances 0.000 description 1
• 229960002261 magnesium phosphate Drugs 0.000 description 1
• 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
• 235000010994 magnesium phosphates Nutrition 0.000 description 1
• 230000036210 malignancy Effects 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 230000028161 membrane depolarization Effects 0.000 description 1
• 201000011475 meningoencephalitis Diseases 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 230000006371 metabolic abnormality Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 description 1
• 229960004023 minocycline Drugs 0.000 description 1
• 230000002438 mitochondrial effect Effects 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 210000005087 mononuclear cell Anatomy 0.000 description 1
• 230000000877 morphologic effect Effects 0.000 description 1
• 230000007659 motor function Effects 0.000 description 1
• 210000002161 motor neuron Anatomy 0.000 description 1
• 230000020763 muscle atrophy Effects 0.000 description 1
• 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical class N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
• 230000017074 necrotic cell death Effects 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 230000008271 nervous system development Effects 0.000 description 1
• 208000028412 nervous system injury Diseases 0.000 description 1
• 230000007472 neurodevelopment Effects 0.000 description 1
• 210000000461 neuroepithelial cell Anatomy 0.000 description 1
• 201000004931 neurofibromatosis Diseases 0.000 description 1
• 230000009251 neurologic dysfunction Effects 0.000 description 1
• 208000015015 neurological dysfunction Diseases 0.000 description 1
• 231100000878 neurological injury Toxicity 0.000 description 1
• 230000002232 neuromuscular Effects 0.000 description 1
• 230000009223 neuronal apoptosis Effects 0.000 description 1
• 230000007996 neuronal plasticity Effects 0.000 description 1
• 230000005015 neuronal process Effects 0.000 description 1
• 230000006576 neuronal survival Effects 0.000 description 1
• 231100000228 neurotoxicity Toxicity 0.000 description 1
• 230000007135 neurotoxicity Effects 0.000 description 1
• 210000000440 neutrophil Anatomy 0.000 description 1
• NXFQHRVNIOXGAQ-YCRREMRBSA-N nitrofurantoin Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)NC(=O)C1 NXFQHRVNIOXGAQ-YCRREMRBSA-N 0.000 description 1
• 229960000564 nitrofurantoin Drugs 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 235000016709 nutrition Nutrition 0.000 description 1
• 210000004273 ophthalmic nerve Anatomy 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002891 organic anions Chemical class 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 230000000399 orthopedic effect Effects 0.000 description 1
• 229910052762 osmium Inorganic materials 0.000 description 1
• SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 229960001592 paclitaxel Drugs 0.000 description 1
• 230000037324 pain perception Effects 0.000 description 1
• 230000008058 pain sensation Effects 0.000 description 1
• 208000021090 palsy Diseases 0.000 description 1
• 229940055726 pantothenic acid Drugs 0.000 description 1
• 235000019161 pantothenic acid Nutrition 0.000 description 1
• 239000011713 pantothenic acid Substances 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 208000012111 paraneoplastic syndrome Diseases 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 244000052769 pathogen Species 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000008289 pathophysiological mechanism Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• MCYTYTUNNNZWOK-LCLOTLQISA-N penetratin Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=CC=C1 MCYTYTUNNNZWOK-LCLOTLQISA-N 0.000 description 1
• 108010043655 penetratin Proteins 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 238000001558 permutation test Methods 0.000 description 1
• 235000020030 perry Nutrition 0.000 description 1
• 230000002688 persistence Effects 0.000 description 1
• 210000001539 phagocyte Anatomy 0.000 description 1
• 230000008782 phagocytosis Effects 0.000 description 1
• 239000008180 pharmaceutical surfactant Substances 0.000 description 1
• 229960002036 phenytoin Drugs 0.000 description 1
• XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
• 125000005496 phosphonium group Chemical group 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 108010017843 platelet-derived growth factor A Proteins 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 231100000614 poison Toxicity 0.000 description 1
• 239000002574 poison Substances 0.000 description 1
• 231100000572 poisoning Toxicity 0.000 description 1
• 230000000607 poisoning effect Effects 0.000 description 1
• 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
• 230000008488 polyadenylation Effects 0.000 description 1
• 201000006292 polyarteritis nodosa Diseases 0.000 description 1
• 238000006116 polymerization reaction Methods 0.000 description 1
• 239000011148 porous material Substances 0.000 description 1
• 238000010149 post-hoc-test Methods 0.000 description 1
• 208000037955 postinfectious encephalomyelitis Diseases 0.000 description 1
• 230000036544 posture Effects 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 230000001376 precipitating effect Effects 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 230000009465 prokaryotic expression Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 230000009023 proprioceptive sensation Effects 0.000 description 1
• 235000019833 protease Nutrition 0.000 description 1
• 230000004952 protein activity Effects 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 208000020016 psychiatric disease Diseases 0.000 description 1
• 239000012264 purified product Substances 0.000 description 1
• 108700043101 rat CXCL12 Proteins 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 238000003259 recombinant expression Methods 0.000 description 1
• 230000002787 reinforcement Effects 0.000 description 1
• 230000004043 responsiveness Effects 0.000 description 1
• 108091008146 restriction endonucleases Proteins 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 238000004062 sedimentation Methods 0.000 description 1
• 230000036362 sensorimotor function Effects 0.000 description 1
• 210000001044 sensory neuron Anatomy 0.000 description 1
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 238000012868 site-directed mutagenesis technique Methods 0.000 description 1
• 208000019116 sleep disease Diseases 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 239000002904 solvent Substances 0.000 description 1
• 230000001148 spastic effect Effects 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 210000000130 stem cell Anatomy 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 210000002536 stromal cell Anatomy 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003456 sulfonamides Chemical class 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 229910021653 sulphate ion Inorganic materials 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 230000035900 sweating Effects 0.000 description 1
• 230000005062 synaptic transmission Effects 0.000 description 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
• KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
• 235000019157 thiamine Nutrition 0.000 description 1
• 229960003495 thiamine Drugs 0.000 description 1
• 239000011721 thiamine Substances 0.000 description 1
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 229950003937 tolonium Drugs 0.000 description 1
• HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000563 toxic property Toxicity 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 230000031998 transcytosis Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 239000012581 transferrin Substances 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 230000007723 transport mechanism Effects 0.000 description 1
• 230000009529 traumatic brain injury Effects 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• 239000013638 trimer Substances 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 230000001228 trophic effect Effects 0.000 description 1
• 208000006961 tropical spastic paraparesis Diseases 0.000 description 1
• 239000012588 trypsin Substances 0.000 description 1
• 231100000397 ulcer Toxicity 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 230000003827 upregulation Effects 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 230000002227 vasoactive effect Effects 0.000 description 1
• 229960003048 vinblastine Drugs 0.000 description 1
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
• 229960004355 vindesine Drugs 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 238000012800 visualization Methods 0.000 description 1
• 208000030401 vitamin deficiency disease Diseases 0.000 description 1
• 150000003722 vitamin derivatives Chemical class 0.000 description 1
• BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
• 229960001600 xylazine Drugs 0.000 description 1
• 229910001845 yogo sapphire Inorganic materials 0.000 description 1
• 229960000523 zalcitabine Drugs 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1