CORD-19-Sentences  

CORD-19:3f9572ae671d876279b4d2cd6b6544b24fb3e52d JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
TextSentencer_T1 0-26 Sentence denotes Cystatins in Immune System
TextSentencer_T1 0-26 Sentence denotes Cystatins in Immune System
TextSentencer_T2 28-36 Sentence denotes Abstract
TextSentencer_T2 28-36 Sentence denotes Abstract
TextSentencer_T3 39-201 Sentence denotes Lysosomal cysteine proteases, the cathepsins, classified as clan C1, 1 were long believed to be responsible for the terminal protein degradation in the lysosomes.
TextSentencer_T3 39-201 Sentence denotes Lysosomal cysteine proteases, the cathepsins, classified as clan C1, 1 were long believed to be responsible for the terminal protein degradation in the lysosomes.
TextSentencer_T4 202-480 Sentence denotes This view has changed since they are involved in a number of important cellular processes, such as antigen presentation, 2 bone resorption, 3 apoptosis 4 and protein processing, 5 as well as several pathologies such as cancer progression, 6 inflammation 7 and neurodegeneration.
TextSentencer_T4 202-480 Sentence denotes This view has changed since they are involved in a number of important cellular processes, such as antigen presentation, 2 bone resorption, 3 apoptosis 4 and protein processing, 5 as well as several pathologies such as cancer progression, 6 inflammation 7 and neurodegeneration.
TextSentencer_T5 481-829 Sentence denotes 8 So far, cathepsin D, an aspartic protease, and cysteine cathespins B, H, L, S and few others were associated with cancer progression. [9] [10] [11] [12] Cysteine cathepsins are single-gene products, but the protein products may be polymorphic, due to allelic variants of the gene, alternative RNA splicing and/or post-translational modifications.
TextSentencer_T5 481-829 Sentence denotes 8 So far, cathepsin D, an aspartic protease, and cysteine cathespins B, H, L, S and few others were associated with cancer progression. [9] [10] [11] [12] Cysteine cathepsins are single-gene products, but the protein products may be polymorphic, due to allelic variants of the gene, alternative RNA splicing and/or post-translational modifications.
TextSentencer_T6 830-1065 Sentence denotes Similar to other proteases, cathepsins are regulated at every level of their biosynthesis, in particular, by their compartmentalization to lysosomes, activation of pro-enzyme forms and ultimately by their endogenous protein inhibitors.
TextSentencer_T6 830-1065 Sentence denotes Similar to other proteases, cathepsins are regulated at every level of their biosynthesis, in particular, by their compartmentalization to lysosomes, activation of pro-enzyme forms and ultimately by their endogenous protein inhibitors.
TextSentencer_T7 1066-1324 Sentence denotes 4, 13, 14 Among them the best characterized are cystatins, which comprise a superfamily of evolutionary related proteins, each consisting of at least one domain of 100-120 amino acid res-Ivyspring International Publisher idues with conserved sequence motifs.
TextSentencer_T7 1066-1324 Sentence denotes 4, 13, 14 Among them the best characterized are cystatins, which comprise a superfamily of evolutionary related proteins, each consisting of at least one domain of 100-120 amino acid res-Ivyspring International Publisher idues with conserved sequence motifs.
TextSentencer_T8 1325-1499 Sentence denotes 4, 13, 14 Cystatins function as reversible, tight-binding inhibitors of cysteine proteases, and generally do not possess specific inhibitory activity to particular cathepsin.
TextSentencer_T8 1325-1499 Sentence denotes 4, 13, 14 Cystatins function as reversible, tight-binding inhibitors of cysteine proteases, and generally do not possess specific inhibitory activity to particular cathepsin.
TextSentencer_T9 1500-1600 Sentence denotes Type I cystatins (the stefins), stefins A and B, are cytosolic proteins, lacking disulphide bridges.
TextSentencer_T9 1500-1600 Sentence denotes Type I cystatins (the stefins), stefins A and B, are cytosolic proteins, lacking disulphide bridges.
TextSentencer_T10 1601-1714 Sentence denotes Type II cystatins are more numerous, comprising at least 14 members (for recent review, see Keppler et al., 15 ).
TextSentencer_T10 1601-1714 Sentence denotes Type II cystatins are more numerous, comprising at least 14 members (for recent review, see Keppler et al., 15 ).
TextSentencer_T11 1715-1781 Sentence denotes They are extracellular proteins containing two disulphide bridges.
TextSentencer_T11 1715-1781 Sentence denotes They are extracellular proteins containing two disulphide bridges.
TextSentencer_T12 1782-2110 Sentence denotes Besides well-known cystatins C, D, E/M, F, S, SA, SN this group contains the male reproductive tract cystatins 8 (CRES, cystatin-related epididymal spermatogenic protein), 9 (testatin), 11 and 12 (cystatin T), the bone marrow-derived cystatin-like molecule CLM (cystatin 13) and the secreted phosphoprotein ssp24 (cystatin 14) .
TextSentencer_T12 1782-2110 Sentence denotes Besides well-known cystatins C, D, E/M, F, S, SA, SN this group contains the male reproductive tract cystatins 8 (CRES, cystatin-related epididymal spermatogenic protein), 9 (testatin), 11 and 12 (cystatin T), the bone marrow-derived cystatin-like molecule CLM (cystatin 13) and the secreted phosphoprotein ssp24 (cystatin 14) .
TextSentencer_T13 2111-2237 Sentence denotes Type III cystatins, the kininogens, are large multifunctional plasma proteins, containing three type II cystatin-like domains.
TextSentencer_T13 2111-2237 Sentence denotes Type III cystatins, the kininogens, are large multifunctional plasma proteins, containing three type II cystatin-like domains.
TextSentencer_T14 2238-2454 Sentence denotes Another two types of cystatins, fetuins and latexins are constituted by two tandem cystatin domains, however, they do not exhibit inhibitory activity against cathepsins, and are not the subject of the present review.
TextSentencer_T14 2238-2454 Sentence denotes Another two types of cystatins, fetuins and latexins are constituted by two tandem cystatin domains, however, they do not exhibit inhibitory activity against cathepsins, and are not the subject of the present review.
TextSentencer_T15 2455-2757 Sentence denotes A broad spectrum of biological roles have been suggested for cystatins, including a role in protein catabolism, regulation of hormone processing and bone resorption, inflammation, antigen presentation and T-cell dependent immune response as well as resistance to various bacterial and viral infections.
TextSentencer_T15 2455-2757 Sentence denotes A broad spectrum of biological roles have been suggested for cystatins, including a role in protein catabolism, regulation of hormone processing and bone resorption, inflammation, antigen presentation and T-cell dependent immune response as well as resistance to various bacterial and viral infections.
TextSentencer_T16 2758-2894 Sentence denotes 16, 17 Cystatins have been suggested as modulators of the proteolytic system in several diseases, including immune disorders and cancer.
TextSentencer_T16 2758-2894 Sentence denotes 16, 17 Cystatins have been suggested as modulators of the proteolytic system in several diseases, including immune disorders and cancer.
TextSentencer_T17 2895-3236 Sentence denotes 9, 16, 18 To highlight the function of cystatins in regulation of proteolysis as well as their functions other than protease inhibition, we review recent finding on the status of type I (stefins A, B) and type II cystatins (cystatins C, F and E/M) in pathologies, including their suppressive vs. promotional function in the tumor immunology.
TextSentencer_T17 2895-3236 Sentence denotes 9, 16, 18 To highlight the function of cystatins in regulation of proteolysis as well as their functions other than protease inhibition, we review recent finding on the status of type I (stefins A, B) and type II cystatins (cystatins C, F and E/M) in pathologies, including their suppressive vs. promotional function in the tumor immunology.
TextSentencer_T18 3237-3453 Sentence denotes Stefin A (also named cystatin A, acid cysteine protease inhibitor, epidermal SH-protease inhibitor) and stefin B (also named cystatin B, neutral cysteine protease inhibitor) are representatives of family I cystatins.
TextSentencer_T18 3237-3453 Sentence denotes Stefin A (also named cystatin A, acid cysteine protease inhibitor, epidermal SH-protease inhibitor) and stefin B (also named cystatin B, neutral cysteine protease inhibitor) are representatives of family I cystatins.
TextSentencer_T19 3454-3596 Sentence denotes Stefins A and B exibit 54% sequence identity, both are a 98-amino acid protein with a molecular mass of 11,175 Da and 11,006 Da, respectively.
TextSentencer_T19 3454-3596 Sentence denotes Stefins A and B exibit 54% sequence identity, both are a 98-amino acid protein with a molecular mass of 11,175 Da and 11,006 Da, respectively.
TextSentencer_T20 3597-3731 Sentence denotes 19, 20 The first three-dimensional structure of a stefin was the crystal structure of the recombinant stefin B in complex with papain.
TextSentencer_T20 3597-3731 Sentence denotes 19, 20 The first three-dimensional structure of a stefin was the crystal structure of the recombinant stefin B in complex with papain.
TextSentencer_T21 3732-3925 Sentence denotes The stefin molecule consists of a five stranded antiparallel β-sheet wrapped around a five turn α-helix with an additional carboxyl-terminal strand that runs along the convex side of the sheet.
TextSentencer_T21 3732-3925 Sentence denotes The stefin molecule consists of a five stranded antiparallel β-sheet wrapped around a five turn α-helix with an additional carboxyl-terminal strand that runs along the convex side of the sheet.
TextSentencer_T22 3926-4067 Sentence denotes The N-terminus and the two β-hairpins form the edge of the wedge shaped surface, which bind into the active site cleft of cysteine proteases.
TextSentencer_T22 3926-4067 Sentence denotes The N-terminus and the two β-hairpins form the edge of the wedge shaped surface, which bind into the active site cleft of cysteine proteases.
TextSentencer_T23 4068-4272 Sentence denotes 21 The three-dimensional structure of stefin A has been determined in solution and in complex with cathepsin H, the latter being similar to stefin B-papain complex with a few distinct differences 19, 22 .
TextSentencer_T23 4068-4272 Sentence denotes 21 The three-dimensional structure of stefin A has been determined in solution and in complex with cathepsin H, the latter being similar to stefin B-papain complex with a few distinct differences 19, 22 .
TextSentencer_T24 4273-4431 Sentence denotes Both, stefin A and stefin B, have been shown to form protein structures known as amyloid fibrils, although stefin A under more hursh conditions than stefin B.
TextSentencer_T24 4273-4431 Sentence denotes Both, stefin A and stefin B, have been shown to form protein structures known as amyloid fibrils, although stefin A under more hursh conditions than stefin B.
TextSentencer_T25 4432-4623 Sentence denotes 23 Recently, the crystal structure of stefin B tetramer has been determined which involves Pro at the position 74 in a cis isomeric state being essential in stefin B amyloid-fibril formation.
TextSentencer_T25 4432-4623 Sentence denotes 23 Recently, the crystal structure of stefin B tetramer has been determined which involves Pro at the position 74 in a cis isomeric state being essential in stefin B amyloid-fibril formation.
TextSentencer_T26 4624-4922 Sentence denotes 24, 25 Stefin A was purified from rat skin as a first identified mammalian cystatin 26 and has been found in other epithelial cells, [27] [28] [29] [30] [31] in neutrophils from the liver, 32 in dendritic reticulum cells of lymphoid tissue, 33 in Hassall's corpuscles and in thymic medullary cells.
TextSentencer_T26 4624-4922 Sentence denotes 24, 25 Stefin A was purified from rat skin as a first identified mammalian cystatin 26 and has been found in other epithelial cells, [27] [28] [29] [30] [31] in neutrophils from the liver, 32 in dendritic reticulum cells of lymphoid tissue, 33 in Hassall's corpuscles and in thymic medullary cells.
TextSentencer_T27 4923-5054 Sentence denotes 34 The selective expression of the inhibitor correlates with the tissues participating in the first-line defence against pathogens.
TextSentencer_T27 4923-5054 Sentence denotes 34 The selective expression of the inhibitor correlates with the tissues participating in the first-line defence against pathogens.
TextSentencer_T28 5055-5303 Sentence denotes Analysis of proteins uniquely involved in the development of the skin and skin immune system revealed strong expression of stefin A in neonatal mouse skin and decreasing with age suggesting an important role in the development of the epidermis 35 .
TextSentencer_T28 5055-5303 Sentence denotes Analysis of proteins uniquely involved in the development of the skin and skin immune system revealed strong expression of stefin A in neonatal mouse skin and decreasing with age suggesting an important role in the development of the epidermis 35 .
TextSentencer_T29 5304-5369 Sentence denotes Stefin B is widely expressed in different cell types and tissues.
TextSentencer_T29 5304-5369 Sentence denotes Stefin B is widely expressed in different cell types and tissues.
TextSentencer_T30 5370-5522 Sentence denotes 20, 36-38 Subcellularly, it was found mainly in the nucleus of proliferating cells and both in the nucleus and in the cytoplasm of differentiated cells.
TextSentencer_T30 5370-5522 Sentence denotes 20, 36-38 Subcellularly, it was found mainly in the nucleus of proliferating cells and both in the nucleus and in the cytoplasm of differentiated cells.
TextSentencer_T31 5523-5615 Sentence denotes 39 It has been suggested that stefin B regulates the activity of cathepsin L in the nucleus.
TextSentencer_T31 5523-5615 Sentence denotes 39 It has been suggested that stefin B regulates the activity of cathepsin L in the nucleus.
TextSentencer_T32 5616-5722 Sentence denotes Nuclear stefin B interacted with cathepsin L and with histones in the nucleus, but it did not bind to DNA.
TextSentencer_T32 5616-5722 Sentence denotes Nuclear stefin B interacted with cathepsin L and with histones in the nucleus, but it did not bind to DNA.
TextSentencer_T33 5723-5872 Sentence denotes Increased expression of stefin B in the nucleus delayed cell cycle progression that was associated with the inhibition of cathepsin L in the nucleus.
TextSentencer_T33 5723-5872 Sentence denotes Increased expression of stefin B in the nucleus delayed cell cycle progression that was associated with the inhibition of cathepsin L in the nucleus.
TextSentencer_T34 5873-6070 Sentence denotes Stefin B could thus play an important role in regulating the proteolytic activity of cathepsin L in the nucleus, protecting substrates such as transcription factors from its proteolytic processing.
TextSentencer_T34 5873-6070 Sentence denotes Stefin B could thus play an important role in regulating the proteolytic activity of cathepsin L in the nucleus, protecting substrates such as transcription factors from its proteolytic processing.
TextSentencer_T35 6071-6073 Sentence denotes 40
TextSentencer_T35 6071-6073 Sentence denotes 40
TextSentencer_T36 6074-6200 Sentence denotes Stefin A is involved in cellular proliferation and could be a useful target for diseases of abnormal proliferative conditions.
TextSentencer_T36 6074-6200 Sentence denotes Stefin A is involved in cellular proliferation and could be a useful target for diseases of abnormal proliferative conditions.
TextSentencer_T37 6201-6414 Sentence denotes Its mRNA level is increased in psoriatic plaques of the psoriasis vulgaris, a common inflammatory disease of the skin, characterized by hyperproliferation of skin cells that ultimately leads to red, scaly plaques.
TextSentencer_T37 6201-6414 Sentence denotes Its mRNA level is increased in psoriatic plaques of the psoriasis vulgaris, a common inflammatory disease of the skin, characterized by hyperproliferation of skin cells that ultimately leads to red, scaly plaques.
TextSentencer_T38 6415-6588 Sentence denotes 41 Polymorphysm in the gene for stefin A has been associated with atopic dermatitis, a chronic inflammatory skin disease often associated with a defective epidermal barrier.
TextSentencer_T38 6415-6588 Sentence denotes 41 Polymorphysm in the gene for stefin A has been associated with atopic dermatitis, a chronic inflammatory skin disease often associated with a defective epidermal barrier.
TextSentencer_T39 6589-6690 Sentence denotes 42, 43 Stefin A is able to protect skin barrier from allergic reactions, including atopic dermatitis.
TextSentencer_T39 6589-6690 Sentence denotes 42, 43 Stefin A is able to protect skin barrier from allergic reactions, including atopic dermatitis.
TextSentencer_T40 6691-6885 Sentence denotes Inhibition of proteolytic activity of major mite allergens, Der f 1 and Der p 1, by stefin A blocks the up-regulation of IL-8 and GM-CSF release from keratinocytes stimulated with the allergens.
TextSentencer_T40 6691-6885 Sentence denotes Inhibition of proteolytic activity of major mite allergens, Der f 1 and Der p 1, by stefin A blocks the up-regulation of IL-8 and GM-CSF release from keratinocytes stimulated with the allergens.
TextSentencer_T41 6886-7045 Sentence denotes 44, 45 Loss-of-function mutations in the gene for stefin A has been identified as the underlying genetic cause of another skin disease, exfoliative ichthyosis.
TextSentencer_T41 6886-7045 Sentence denotes 44, 45 Loss-of-function mutations in the gene for stefin A has been identified as the underlying genetic cause of another skin disease, exfoliative ichthyosis.
TextSentencer_T42 7046-7345 Sentence denotes 46 Stefin B was found to form a multi-protein complex specific to the cerebellum with five other proteins and none of them is a protease: the protein kinase C receptor (RACK-1), brain β-spectrin, the neurofilament light chain (NF-L), one protein from the myotubularin family and one unknown protein.
TextSentencer_T42 7046-7345 Sentence denotes 46 Stefin B was found to form a multi-protein complex specific to the cerebellum with five other proteins and none of them is a protease: the protein kinase C receptor (RACK-1), brain β-spectrin, the neurofilament light chain (NF-L), one protein from the myotubularin family and one unknown protein.
TextSentencer_T43 7346-7506 Sentence denotes Stefin B multiprotein complex is proposed to have a specific cerebellar function and the loss of this function might contribute to the disease in EPM1 patients.
TextSentencer_T43 7346-7506 Sentence denotes Stefin B multiprotein complex is proposed to have a specific cerebellar function and the loss of this function might contribute to the disease in EPM1 patients.
TextSentencer_T44 7507-7648 Sentence denotes 47 EPM1 is a degenerative disease of the central nervous system also known as progressive myoclonus epilepsy of the Unverricht-Lundborg type.
TextSentencer_T44 7507-7648 Sentence denotes 47 EPM1 is a degenerative disease of the central nervous system also known as progressive myoclonus epilepsy of the Unverricht-Lundborg type.
TextSentencer_T45 7649-7907 Sentence denotes Altogether 10 different mutations in stefin B gene underlying EPM1 have been reported, of these the most common change an expansion of a normally polymorphic 12-nucleotide repeat in the promoter region is found that is associated with reduced protein levels.
TextSentencer_T45 7649-7907 Sentence denotes Altogether 10 different mutations in stefin B gene underlying EPM1 have been reported, of these the most common change an expansion of a normally polymorphic 12-nucleotide repeat in the promoter region is found that is associated with reduced protein levels.
TextSentencer_T46 7908-8204 Sentence denotes 48 Five different mutations in the coding region of the stefin B gene were found causing protein truncation (R68X), frameshift (K73fsX2) and missense mutations (G4R, Q71P and G50E). [49] [50] [51] [52] [53] Stefin B normally localizes in the nucleus, cytoplasm and also associates with lysosomes.
TextSentencer_T46 7908-8204 Sentence denotes 48 Five different mutations in the coding region of the stefin B gene were found causing protein truncation (R68X), frameshift (K73fsX2) and missense mutations (G4R, Q71P and G50E). [49] [50] [51] [52] [53] Stefin B normally localizes in the nucleus, cytoplasm and also associates with lysosomes.
TextSentencer_T47 8205-8318 Sentence denotes The K73fsX2-truncated mutant protein localizes to cytoplasm and nucleus, whereas R68X mutant is rapidly degraded.
TextSentencer_T47 8205-8318 Sentence denotes The K73fsX2-truncated mutant protein localizes to cytoplasm and nucleus, whereas R68X mutant is rapidly degraded.
TextSentencer_T48 8319-8462 Sentence denotes Two missense mutations, G4R affecting the highly conserved glycine, critical for cathepsin binding, and Q71P, fail to associate with lysosomes.
TextSentencer_T48 8319-8462 Sentence denotes Two missense mutations, G4R affecting the highly conserved glycine, critical for cathepsin binding, and Q71P, fail to associate with lysosomes.
TextSentencer_T49 8463-8627 Sentence denotes These data imply an important lysosome-associated function for stefin B and suggest that loss of this association contributes to the molecular pathogenesis of EPM1.
TextSentencer_T49 8463-8627 Sentence denotes These data imply an important lysosome-associated function for stefin B and suggest that loss of this association contributes to the molecular pathogenesis of EPM1.
TextSentencer_T50 8628-8865 Sentence denotes 53 Accumulation of protein agregates characterize many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease, dementia, multiple system atrophy, Huntington's disease, and the transmissible "prion" dementias.
TextSentencer_T50 8628-8865 Sentence denotes 53 Accumulation of protein agregates characterize many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease, dementia, multiple system atrophy, Huntington's disease, and the transmissible "prion" dementias.
TextSentencer_T51 8866-8992 Sentence denotes 54, 55 Amiloid-β (Aβ) is a soluble peptide, but can form aggregates, either oligomeric or fibrillar that are neurotoxic in AD.
TextSentencer_T51 8866-8992 Sentence denotes 54, 55 Amiloid-β (Aβ) is a soluble peptide, but can form aggregates, either oligomeric or fibrillar that are neurotoxic in AD.
TextSentencer_T52 8993-9087 Sentence denotes 56 Stefin B has been found to be an Aβ-binding protein thus it is likely to have a role in AD.
TextSentencer_T52 8993-9087 Sentence denotes 56 Stefin B has been found to be an Aβ-binding protein thus it is likely to have a role in AD.
TextSentencer_T53 9088-9239 Sentence denotes It interacts with Aβ in vitro and in cells and is supposed to have a "chaperone-like" function with binding the Aβ and inhibiting its fibril formation.
TextSentencer_T53 9088-9239 Sentence denotes It interacts with Aβ in vitro and in cells and is supposed to have a "chaperone-like" function with binding the Aβ and inhibiting its fibril formation.
TextSentencer_T54 9240-9242 Sentence denotes 57
TextSentencer_T54 9240-9242 Sentence denotes 57
TextSentencer_T55 9243-9386 Sentence denotes Among type II cystatins, the most prominent cystatins in immune cells are cystatins C and F, the former being the most abundant human cystatin.
TextSentencer_T55 9243-9386 Sentence denotes Among type II cystatins, the most prominent cystatins in immune cells are cystatins C and F, the former being the most abundant human cystatin.
TextSentencer_T56 9387-9517 Sentence denotes Cystatin C was discovered first as a 'post-γ-globulin' or 'γ-trace' and was the first cystatin determined for amino acid sequence.
TextSentencer_T56 9387-9517 Sentence denotes Cystatin C was discovered first as a 'post-γ-globulin' or 'γ-trace' and was the first cystatin determined for amino acid sequence.
TextSentencer_T57 9518-9633 Sentence denotes 58 Later it was shown that its amino acid sequence was highly similar to cystatin, isolated from chicken egg white.
TextSentencer_T57 9518-9633 Sentence denotes 58 Later it was shown that its amino acid sequence was highly similar to cystatin, isolated from chicken egg white.
TextSentencer_T58 9634-9738 Sentence denotes 59 Mature human cystatin C is composed of 120 amino acid residues and has a molecular mass of 13,343 Da.
TextSentencer_T58 9634-9738 Sentence denotes 59 Mature human cystatin C is composed of 120 amino acid residues and has a molecular mass of 13,343 Da.
TextSentencer_T59 9739-9857 Sentence denotes The cystatin C cDNA sequence revealed that cystatin C is synthesized as a preprotein with a 26 residue signal peptide.
TextSentencer_T59 9739-9857 Sentence denotes The cystatin C cDNA sequence revealed that cystatin C is synthesized as a preprotein with a 26 residue signal peptide.
TextSentencer_T60 9858-9986 Sentence denotes 60 The gene, encoding cystatin C is typical house-keeping gene type, which is expressed in a variety of human tissues and cells.
TextSentencer_T60 9858-9986 Sentence denotes 60 The gene, encoding cystatin C is typical house-keeping gene type, which is expressed in a variety of human tissues and cells.
TextSentencer_T61 9987-10201 Sentence denotes However, like the most of other type II cystatins, cystatin C is secreted and can be found in high concentrations in body fluids, in particular high levels have been found in seminal plasma and cerebrospinal fluid.
TextSentencer_T61 9987-10201 Sentence denotes However, like the most of other type II cystatins, cystatin C is secreted and can be found in high concentrations in body fluids, in particular high levels have been found in seminal plasma and cerebrospinal fluid.
TextSentencer_T62 10202-10409 Sentence denotes Cystatin C is strong inhibitor of all papain-like proteases (clan C1) 61, 62 and asparaginyl endopeptidase/legumain (clan C13) 63 and could be seen as a major human extracellular cysteine protease inhibitor.
TextSentencer_T62 10202-10409 Sentence denotes Cystatin C is strong inhibitor of all papain-like proteases (clan C1) 61, 62 and asparaginyl endopeptidase/legumain (clan C13) 63 and could be seen as a major human extracellular cysteine protease inhibitor.
TextSentencer_T63 10410-10641 Sentence denotes Cystatin C has been suggested as regulating cathepsin S activity and invariant chain (Ii) processing in dendritic cells (DCs), 64 however, further studies excluded a role in controlling MHC II-dependent antigen presentation in DCs.
TextSentencer_T63 10410-10641 Sentence denotes Cystatin C has been suggested as regulating cathepsin S activity and invariant chain (Ii) processing in dendritic cells (DCs), 64 however, further studies excluded a role in controlling MHC II-dependent antigen presentation in DCs.
TextSentencer_T64 10642-10894 Sentence denotes 65 Additionally, the maturation process of DCs leads to reduced levels of cystatin C and colocalization studies do not support intracellular interactions among cystatin C and its potential target enzymes cathepsins H, L and S in immature or mature DCs.
TextSentencer_T64 10642-10894 Sentence denotes 65 Additionally, the maturation process of DCs leads to reduced levels of cystatin C and colocalization studies do not support intracellular interactions among cystatin C and its potential target enzymes cathepsins H, L and S in immature or mature DCs.
TextSentencer_T65 10895-11021 Sentence denotes 66 A better candidate for regulating the proteolytic activity of cysteine proteases within the DCs was shown to be cystatin F.
TextSentencer_T65 10895-11021 Sentence denotes 66 A better candidate for regulating the proteolytic activity of cysteine proteases within the DCs was shown to be cystatin F.
TextSentencer_T66 11022-11079 Sentence denotes 67 Cystatin F was discovered by three independent groups.
TextSentencer_T66 11022-11079 Sentence denotes 67 Cystatin F was discovered by three independent groups.
TextSentencer_T67 11080-11187 Sentence denotes Two of them identified the new inhibitor by cDNA cloning and named it leukocystatin and cystatin F 68, 69 .
TextSentencer_T67 11080-11187 Sentence denotes Two of them identified the new inhibitor by cDNA cloning and named it leukocystatin and cystatin F 68, 69 .
TextSentencer_T68 11188-11348 Sentence denotes The third group found overexpressed mRNA encoding cystatin F in liver metastatic tumors and identified it as CMAP (cystatin-like metastasis associated protein).
TextSentencer_T68 11188-11348 Sentence denotes The third group found overexpressed mRNA encoding cystatin F in liver metastatic tumors and identified it as CMAP (cystatin-like metastasis associated protein).
TextSentencer_T69 11349-11460 Sentence denotes 70 Human cystatin F is synthesized as a 145 amino acids pre-protein with a putative 19 residues signal peptide.
TextSentencer_T69 11349-11460 Sentence denotes 70 Human cystatin F is synthesized as a 145 amino acids pre-protein with a putative 19 residues signal peptide.
TextSentencer_T70 11461-11675 Sentence denotes 68, 69 Although it is made with a signal sequence, only a small proportion is secreted 69 and importantly, it is secreted as a disulphide-linked dimer 71 which is inactive until it is reduced to its monomeric form.
TextSentencer_T70 11461-11675 Sentence denotes 68, 69 Although it is made with a signal sequence, only a small proportion is secreted 69 and importantly, it is secreted as a disulphide-linked dimer 71 which is inactive until it is reduced to its monomeric form.
TextSentencer_T71 11676-11823 Sentence denotes 72 It is glycosylated 68, 69 and mannose-6-phosphate modification of its N-linked saccharides is used for targeting to the endosomes and lysosomes.
TextSentencer_T71 11676-11823 Sentence denotes 72 It is glycosylated 68, 69 and mannose-6-phosphate modification of its N-linked saccharides is used for targeting to the endosomes and lysosomes.
TextSentencer_T72 11824-12017 Sentence denotes 73 Glycosylation at Asn 62 is proposed to protect the intermolecular disulphide from reduction, explaining unusually strong reducing conditions needed to monomerize dimeric cystatin F in vitro.
TextSentencer_T72 11824-12017 Sentence denotes 73 Glycosylation at Asn 62 is proposed to protect the intermolecular disulphide from reduction, explaining unusually strong reducing conditions needed to monomerize dimeric cystatin F in vitro.
TextSentencer_T73 12018-12200 Sentence denotes 72, 74 Inactive dimer to active monomer con-version is also achieved with proteolitic cleavage by so far unidentified protease action on the extended N-terminal region of cystatin F.
TextSentencer_T73 12018-12200 Sentence denotes 72, 74 Inactive dimer to active monomer con-version is also achieved with proteolitic cleavage by so far unidentified protease action on the extended N-terminal region of cystatin F.
TextSentencer_T74 12201-12349 Sentence denotes 75 Being glycosylated, inacive cystatin F can be internalized through the mannose-6-phosphate receptor pathway and activated within different cells.
TextSentencer_T74 12201-12349 Sentence denotes 75 Being glycosylated, inacive cystatin F can be internalized through the mannose-6-phosphate receptor pathway and activated within different cells.
TextSentencer_T75 12350-12552 Sentence denotes 73 All these facts strongly imply on intracellular action of cystatin F as well as on "in trans" activity of its secreted inactive inhibitor which can be internalized and activated inside another cells.
TextSentencer_T75 12350-12552 Sentence denotes 73 All these facts strongly imply on intracellular action of cystatin F as well as on "in trans" activity of its secreted inactive inhibitor which can be internalized and activated inside another cells.
TextSentencer_T76 12553-12704 Sentence denotes Cystatin F tightly inhibits cathepsins F, K, V, whereas cathepsins S and H are inhibited with lower affinities and cathepsin X is not inhibited at all.
TextSentencer_T76 12553-12704 Sentence denotes Cystatin F tightly inhibits cathepsins F, K, V, whereas cathepsins S and H are inhibited with lower affinities and cathepsin X is not inhibited at all.
TextSentencer_T77 12705-12931 Sentence denotes 69 , 76 C13 cysteine protease involved in antigen pocessing, mammalian legumain or asparaginyl endopeptidase (AEP), is also inhibited by cystatin F although it showes reduced affinity for AEP compared with cystatins C and E/M.
TextSentencer_T77 12705-12931 Sentence denotes 69 , 76 C13 cysteine protease involved in antigen pocessing, mammalian legumain or asparaginyl endopeptidase (AEP), is also inhibited by cystatin F although it showes reduced affinity for AEP compared with cystatins C and E/M.
TextSentencer_T78 12932-13078 Sentence denotes 63 The inhibitor is expressed selectively in immune cells such as cytotoxic T cells, natural killer cells (NK cells), monocytes, DCs ( Figure 1 ).
TextSentencer_T78 12932-13078 Sentence denotes 63 The inhibitor is expressed selectively in immune cells such as cytotoxic T cells, natural killer cells (NK cells), monocytes, DCs ( Figure 1 ).
TextSentencer_T79 13079-13186 Sentence denotes 67-69, 77, 78 Its levels and localization are controlled according to the physiological state of the cells.
TextSentencer_T79 13079-13186 Sentence denotes 67-69, 77, 78 Its levels and localization are controlled according to the physiological state of the cells.
TextSentencer_T80 13187-13451 Sentence denotes It is strongly up-regulated in monocyte-derived DCs undergoing LPS-induced maturation and downregulated in TPA-(causing monocytic differentiation towards a granulocytic pathway) or ATRA-(causing monocytic differentiation towards macrophages) stimulated U937 cells.
TextSentencer_T80 13187-13451 Sentence denotes It is strongly up-regulated in monocyte-derived DCs undergoing LPS-induced maturation and downregulated in TPA-(causing monocytic differentiation towards a granulocytic pathway) or ATRA-(causing monocytic differentiation towards macrophages) stimulated U937 cells.
TextSentencer_T81 13452-13695 Sentence denotes 77, 79 The unique features of cystatin F suggests that this immune-cell specific inhibitor plays a role in immune response-related processes through inhibition of specific enzyme targets, even though the details of its role remain unexplained.
TextSentencer_T81 13452-13695 Sentence denotes 77, 79 The unique features of cystatin F suggests that this immune-cell specific inhibitor plays a role in immune response-related processes through inhibition of specific enzyme targets, even though the details of its role remain unexplained.
TextSentencer_T82 13696-13915 Sentence denotes It is likely that in DCs, cystatin F could regulate the activity of cathepsin L and thus controlling the processing of procathepsin X, which promotes cell adhesion via activation of Mac-1 (CD11b/CD18) integrin receptor.
TextSentencer_T82 13696-13915 Sentence denotes It is likely that in DCs, cystatin F could regulate the activity of cathepsin L and thus controlling the processing of procathepsin X, which promotes cell adhesion via activation of Mac-1 (CD11b/CD18) integrin receptor.
TextSentencer_T83 13916-14127 Sentence denotes 67 One of the protease targets of cystatin F is cathepsin C 75 , the cysteine protease that activates the granzymes in cytotoxic T cells, NK cells and several of effector proteases of neutrophils and mast cells.
TextSentencer_T83 13916-14127 Sentence denotes 67 One of the protease targets of cystatin F is cathepsin C 75 , the cysteine protease that activates the granzymes in cytotoxic T cells, NK cells and several of effector proteases of neutrophils and mast cells.
TextSentencer_T84 14128-14225 Sentence denotes 75, 80, 81 Cystain F is a strong inhibitor of cathepsin C only as an N-terminally truncated form.
TextSentencer_T84 14128-14225 Sentence denotes 75, 80, 81 Cystain F is a strong inhibitor of cathepsin C only as an N-terminally truncated form.
TextSentencer_T85 14226-14410 Sentence denotes 75 Our recent work suggests potential regulation of split anergy in NK cells through inhibition of cathepsin C and consequently downstream regulation of granzymes (Manuscript in prep).
TextSentencer_T85 14226-14410 Sentence denotes 75 Our recent work suggests potential regulation of split anergy in NK cells through inhibition of cathepsin C and consequently downstream regulation of granzymes (Manuscript in prep).
TextSentencer_T86 14411-14634 Sentence denotes Recent work by Dr. Jewett and colleagues indicate that induction of split anergy in NK cells may be an important physiological step required for the conditioning of the NK cells to support differentiation of the stem cells.
TextSentencer_T86 14411-14634 Sentence denotes Recent work by Dr. Jewett and colleagues indicate that induction of split anergy in NK cells may be an important physiological step required for the conditioning of the NK cells to support differentiation of the stem cells.
TextSentencer_T87 14635-14852 Sentence denotes In this regard they proposed that conditioned or anergized NK cells may play a significant role in differentiation of the cells by providing critical signals via secreted cytokines as well as direct cell-cell contact.
TextSentencer_T87 14635-14852 Sentence denotes In this regard they proposed that conditioned or anergized NK cells may play a significant role in differentiation of the cells by providing critical signals via secreted cytokines as well as direct cell-cell contact.
TextSentencer_T88 14853-15152 Sentence denotes To be conditioned to drive differentiation, NK cells may have to first receive signals through their key surface receptors either from stem cells or other immune effectors or fibroblasts in the inflammatory microenvironment and lose cytotoxicity and gain cytokine producing phenotype (split anergy).
TextSentencer_T88 14853-15152 Sentence denotes To be conditioned to drive differentiation, NK cells may have to first receive signals through their key surface receptors either from stem cells or other immune effectors or fibroblasts in the inflammatory microenvironment and lose cytotoxicity and gain cytokine producing phenotype (split anergy).
TextSentencer_T89 15153-15318 Sentence denotes These alterations in NK cell effector function will ultimately aid in driving differentiation of a population of surviving healthy as well as transformed stem cells.
TextSentencer_T89 15153-15318 Sentence denotes These alterations in NK cell effector function will ultimately aid in driving differentiation of a population of surviving healthy as well as transformed stem cells.
TextSentencer_T90 15319-15520 Sentence denotes Regulation of cystatin F and consequently cathepsin C and granzymes by NK cell surface receptors could be the mechanism which conditions NK cells to undergo split anergy and become regulatory NK cells.
TextSentencer_T90 15319-15520 Sentence denotes Regulation of cystatin F and consequently cathepsin C and granzymes by NK cell surface receptors could be the mechanism which conditions NK cells to undergo split anergy and become regulatory NK cells.
TextSentencer_T91 15521-15570 Sentence denotes Part of image is magnified in lower right corner.
TextSentencer_T91 15521-15570 Sentence denotes Part of image is magnified in lower right corner.
TextSentencer_T92 15571-15690 Sentence denotes The white colour indicates colocalization of two labelled antigens, confirming the presence of cystatin F in lysosomes.
TextSentencer_T92 15571-15690 Sentence denotes The white colour indicates colocalization of two labelled antigens, confirming the presence of cystatin F in lysosomes.
TextSentencer_T93 15691-15782 Sentence denotes The threshold value for colocalization was set to one half of the maximal brightness level.
TextSentencer_T93 15691-15782 Sentence denotes The threshold value for colocalization was set to one half of the maximal brightness level.
TextSentencer_T94 15783-15916 Sentence denotes The mask of the pixels above the threshold in both channels (significant colocalization, blue colour) and the contour plot are shown.
TextSentencer_T94 15783-15916 Sentence denotes The mask of the pixels above the threshold in both channels (significant colocalization, blue colour) and the contour plot are shown.
TextSentencer_T95 15917-16083 Sentence denotes 67 For cystatin M a downregulated mRNA in metastatic breast tumor cells was identified by differential display when compared to normal and primary breast tumor cells.
TextSentencer_T95 15917-16083 Sentence denotes 67 For cystatin M a downregulated mRNA in metastatic breast tumor cells was identified by differential display when compared to normal and primary breast tumor cells.
TextSentencer_T96 16084-16219 Sentence denotes 82 Independently, the same molecule was found by others in cDNA libraries derived from epithelial cells, and was designated cystatin E.
TextSentencer_T96 16084-16219 Sentence denotes 82 Independently, the same molecule was found by others in cDNA libraries derived from epithelial cells, and was designated cystatin E.
TextSentencer_T97 16220-16395 Sentence denotes 83 Cystatin E/M is a 14.5 kDa secreted protein that has an overall structure similar to other family II cystatins, such as a signal peptide and two intrachain disulfide bonds.
TextSentencer_T97 16220-16395 Sentence denotes 83 Cystatin E/M is a 14.5 kDa secreted protein that has an overall structure similar to other family II cystatins, such as a signal peptide and two intrachain disulfide bonds.
TextSentencer_T98 16396-16542 Sentence denotes Like cystatin F 68, 69 , it possesses the unusual characteristic of being a glycoprotein, carrying an N-linked carbohydrate chain at position 108.
TextSentencer_T98 16396-16542 Sentence denotes Like cystatin F 68, 69 , it possesses the unusual characteristic of being a glycoprotein, carrying an N-linked carbohydrate chain at position 108.
TextSentencer_T99 16543-16808 Sentence denotes 82, 83 This protein is only distantly related to the other known family members as reflected by the genomic position of the cystatin E/M gene on chromosome 11q13 84 , whereas all other family II cystatin genes are clustered in a narrow region on chromosome 20p11.2.
TextSentencer_T99 16543-16808 Sentence denotes 82, 83 This protein is only distantly related to the other known family members as reflected by the genomic position of the cystatin E/M gene on chromosome 11q13 84 , whereas all other family II cystatin genes are clustered in a narrow region on chromosome 20p11.2.
TextSentencer_T100 16809-16936 Sentence denotes 85 Cystatin E/M is synthesized as a pre-protein with a putative 28 residues while mature cystatin E/M contains 121 amino acids.
TextSentencer_T100 16809-16936 Sentence denotes 85 Cystatin E/M is synthesized as a pre-protein with a putative 28 residues while mature cystatin E/M contains 121 amino acids.
TextSentencer_T101 16937-17060 Sentence denotes 83 High expression levels are largely confined to skin epithelia, which emphasizes its prominent role in cutaneous biology.
TextSentencer_T101 16937-17060 Sentence denotes 83 High expression levels are largely confined to skin epithelia, which emphasizes its prominent role in cutaneous biology.
TextSentencer_T102 17061-17188 Sentence denotes 86 Its expression was also reported recently in breast tissue 87 and in oligodendrocyteand astrocyte-like cells of human brain.
TextSentencer_T102 17061-17188 Sentence denotes 86 Its expression was also reported recently in breast tissue 87 and in oligodendrocyteand astrocyte-like cells of human brain.
TextSentencer_T103 17189-17345 Sentence denotes 88 Cystatin E/M is a high-affinity inhibitor of cathepsins V, L 89 and asparaginyl endopeptidase/legumain, 63 with lower affinity it binds also cathepsin B.
TextSentencer_T103 17189-17345 Sentence denotes 88 Cystatin E/M is a high-affinity inhibitor of cathepsins V, L 89 and asparaginyl endopeptidase/legumain, 63 with lower affinity it binds also cathepsin B.
TextSentencer_T104 17346-17482 Sentence denotes 83 In vivo mouse models have revealed that cystatin E/M is a key molecule in a biochemical pathway that controls skin barrier formation.
TextSentencer_T104 17346-17482 Sentence denotes 83 In vivo mouse models have revealed that cystatin E/M is a key molecule in a biochemical pathway that controls skin barrier formation.
TextSentencer_T105 17483-17697 Sentence denotes 90, 91 The terminal stage of the differentiation process of keratinocytes is desquamation, which involves degradation of lipids in the intercellular spaces and loss of residual intercellular desmosomal connections.
TextSentencer_T105 17483-17697 Sentence denotes 90, 91 The terminal stage of the differentiation process of keratinocytes is desquamation, which involves degradation of lipids in the intercellular spaces and loss of residual intercellular desmosomal connections.
TextSentencer_T106 17698-17819 Sentence denotes Cells reaching the skin surface are continuously sloughed and replaced by inner cells differentiating and moving outward.
TextSentencer_T106 17698-17819 Sentence denotes Cells reaching the skin surface are continuously sloughed and replaced by inner cells differentiating and moving outward.
TextSentencer_T107 17820-18115 Sentence denotes 92 Cystatin E/M could have a role in desquamation by the regulation of cathepsin V protease activity or could regulate cathepsin L and legumain activities cosslinking of structural proteins by transglutaminase 3 in the keratinocyte differentiation process of the epidermis and the hair follicle.
TextSentencer_T107 17820-18115 Sentence denotes 92 Cystatin E/M could have a role in desquamation by the regulation of cathepsin V protease activity or could regulate cathepsin L and legumain activities cosslinking of structural proteins by transglutaminase 3 in the keratinocyte differentiation process of the epidermis and the hair follicle.
TextSentencer_T108 18116-18469 Sentence denotes 93 In addition, it might also be involved in the regulation of cathepsin D activity, as it is known that cathepsin L can process and activate cathepsin D 94, 95 and mature cathepsin D is also important in the desquamation process of the skin. [96] [97] [98] The studies regarding implication of other type II cystatins in immune system are not numerous.
TextSentencer_T108 18116-18469 Sentence denotes 93 In addition, it might also be involved in the regulation of cathepsin D activity, as it is known that cathepsin L can process and activate cathepsin D 94, 95 and mature cathepsin D is also important in the desquamation process of the skin. [96] [97] [98] The studies regarding implication of other type II cystatins in immune system are not numerous.
TextSentencer_T109 18470-18889 Sentence denotes Cystatins S, SN and SA were first isolated from human saliva and later identified as a cysteine protease inhibitors and their role in controlling cysteine proteases derived from bacteria has been suggested. [99] [100] [101] [102] These three proteins with similar sequence (88% identity at the protein level) are distantly related to cystatin D (less then 60% identity at the protein level with cystatins S, SN and SA).
TextSentencer_T109 18470-18889 Sentence denotes Cystatins S, SN and SA were first isolated from human saliva and later identified as a cysteine protease inhibitors and their role in controlling cysteine proteases derived from bacteria has been suggested. [99] [100] [101] [102] These three proteins with similar sequence (88% identity at the protein level) are distantly related to cystatin D (less then 60% identity at the protein level with cystatins S, SN and SA).
TextSentencer_T110 18890-19014 Sentence denotes 103 Although they are possessing inhibitory activity, they are all poorer inhibitors of cysteine cathepsins than cystatin C.
TextSentencer_T110 18890-19014 Sentence denotes 103 Although they are possessing inhibitory activity, they are all poorer inhibitors of cysteine cathepsins than cystatin C.
TextSentencer_T111 19015-19554 Sentence denotes 104 Inhibition of bacterial cysteine proteases have been tested by cystatins C, SN, S and chicken cystatin and they are generaly inactive against bacterial cysteine proteases. [105] [106] [107] In contrast to bacterial cysteine proteases, they are more efficient against cysteine proteases from parasits; for example, cystatins SA and SN are inhibitors of trypanosome cruzain 108 , chicken cystatin inhibits congopain from Trypanosoma congolense 109 and cruzipain, the major cysteine proteinase of the protozoan parasite Trypanosoma cruzi.
TextSentencer_T111 19015-19554 Sentence denotes 104 Inhibition of bacterial cysteine proteases have been tested by cystatins C, SN, S and chicken cystatin and they are generaly inactive against bacterial cysteine proteases. [105] [106] [107] In contrast to bacterial cysteine proteases, they are more efficient against cysteine proteases from parasits; for example, cystatins SA and SN are inhibitors of trypanosome cruzain 108 , chicken cystatin inhibits congopain from Trypanosoma congolense 109 and cruzipain, the major cysteine proteinase of the protozoan parasite Trypanosoma cruzi.
TextSentencer_T112 19555-19657 Sentence denotes 110 These results suggest a possible defensive role for the host's cystatins after parasite infection.
TextSentencer_T112 19555-19657 Sentence denotes 110 These results suggest a possible defensive role for the host's cystatins after parasite infection.
TextSentencer_T113 19658-19790 Sentence denotes Cystatin SN has been found also in dendritic cells exposed to Toxoplasma gondii 111 and it could thus modulate antigen presentation.
TextSentencer_T113 19658-19790 Sentence denotes Cystatin SN has been found also in dendritic cells exposed to Toxoplasma gondii 111 and it could thus modulate antigen presentation.
TextSentencer_T114 19791-19936 Sentence denotes Salivary cystatins may have a role in the host defense mechanism against virus infections as they can interfere with events in viral replication.
TextSentencer_T114 19791-19936 Sentence denotes Salivary cystatins may have a role in the host defense mechanism against virus infections as they can interfere with events in viral replication.
TextSentencer_T115 19937-20120 Sentence denotes Cystatin D has been found to be a potent inhibitor of coronavirus replication 112 and cystatins S, SA and SN can suppress the infectivity of adenovirus 113 and herpes simplex virus 1.
TextSentencer_T115 19937-20120 Sentence denotes Cystatin D has been found to be a potent inhibitor of coronavirus replication 112 and cystatins S, SA and SN can suppress the infectivity of adenovirus 113 and herpes simplex virus 1.
TextSentencer_T116 20121-20252 Sentence denotes 114 Human genom contains several related genes encoding gycoproteins that possess sequence similarity with other type II cystatins.
TextSentencer_T116 20121-20252 Sentence denotes 114 Human genom contains several related genes encoding gycoproteins that possess sequence similarity with other type II cystatins.
TextSentencer_T117 20253-20379 Sentence denotes The shared characteristic of three subgroup members is an expression pattern limited primarily to the male reproductive tract.
TextSentencer_T117 20253-20379 Sentence denotes The shared characteristic of three subgroup members is an expression pattern limited primarily to the male reproductive tract.
TextSentencer_T118 20380-20583 Sentence denotes Testatin 115 and cystatin T 116 are specifically expressed in the testis and cystatin-related epididymal spermatogenic protein (CRES) exhibits highly tissue-specific expression in the reproductive tract.
TextSentencer_T118 20380-20583 Sentence denotes Testatin 115 and cystatin T 116 are specifically expressed in the testis and cystatin-related epididymal spermatogenic protein (CRES) exhibits highly tissue-specific expression in the reproductive tract.
TextSentencer_T119 20584-20737 Sentence denotes 117 Although they possess a typical C-terminal PW motif, they lack the N-terminal glycine and motif QXVXG important for inhibition of cysteine proteases.
TextSentencer_T119 20584-20737 Sentence denotes 117 Although they possess a typical C-terminal PW motif, they lack the N-terminal glycine and motif QXVXG important for inhibition of cysteine proteases.
TextSentencer_T120 20738-20852 Sentence denotes Changes in cystatin C expression and localization have been associated with various neurodegenerative pathologies.
TextSentencer_T120 20738-20852 Sentence denotes Changes in cystatin C expression and localization have been associated with various neurodegenerative pathologies.
TextSentencer_T121 20853-21076 Sentence denotes For example, a point mutation in the cystatin C gene, resulting in the substitution of Leu to Gln, is responsible for the dominantly inherited icelandic type of amyloidosis, hereditary cystatin C amyloid angiopathy (HCCAA).
TextSentencer_T121 20853-21076 Sentence denotes For example, a point mutation in the cystatin C gene, resulting in the substitution of Leu to Gln, is responsible for the dominantly inherited icelandic type of amyloidosis, hereditary cystatin C amyloid angiopathy (HCCAA).
TextSentencer_T122 21077-21182 Sentence denotes Patients with this disease suffer from successive brain hemorrhages concluding in death at the age of 30.
TextSentencer_T122 21077-21182 Sentence denotes Patients with this disease suffer from successive brain hemorrhages concluding in death at the age of 30.
TextSentencer_T123 21183-21413 Sentence denotes In first line the formation of cystatin C aggregates are responsible for the outcome and progression of the disease, however, the loss of inhibitory function due to aggregation and lower concentration in brain can not be excluded.
TextSentencer_T123 21183-21413 Sentence denotes In first line the formation of cystatin C aggregates are responsible for the outcome and progression of the disease, however, the loss of inhibitory function due to aggregation and lower concentration in brain can not be excluded.
TextSentencer_T124 21414-21574 Sentence denotes 118 The levels of cystatin C were highly reduced in cerebrospinal fluid of individuals suffering from multiple sclerosis (MS) compared with healthy individuals.
TextSentencer_T124 21414-21574 Sentence denotes 118 The levels of cystatin C were highly reduced in cerebrospinal fluid of individuals suffering from multiple sclerosis (MS) compared with healthy individuals.
TextSentencer_T125 21575-21776 Sentence denotes Its low concentration suggests that the inhibition of cysteine proteinases is impaired in this disease; hence higher activity of cysteine proteinases could initiate or increase the breakdown of myelin.
TextSentencer_T125 21575-21776 Sentence denotes Its low concentration suggests that the inhibition of cysteine proteinases is impaired in this disease; hence higher activity of cysteine proteinases could initiate or increase the breakdown of myelin.
TextSentencer_T126 21777-21847 Sentence denotes 119 Cystatin C was shown to be implicated in Alzheimer's disease (AD).
TextSentencer_T126 21777-21847 Sentence denotes 119 Cystatin C was shown to be implicated in Alzheimer's disease (AD).
TextSentencer_T127 21848-21998 Sentence denotes It co-deposits with amyloid-beta (Aβ) in amyloid plaques of AD patients 120 , associates with Aβ and inhibits Aβ oligomerization in vitro and in vivo.
TextSentencer_T127 21848-21998 Sentence denotes It co-deposits with amyloid-beta (Aβ) in amyloid plaques of AD patients 120 , associates with Aβ and inhibits Aβ oligomerization in vitro and in vivo.
TextSentencer_T128 21999-22123 Sentence denotes 121, 122 Thus, cystatin C could protect the brain from amyloid-induced toxicity and may have therapetic implications for AD.
TextSentencer_T128 21999-22123 Sentence denotes 121, 122 Thus, cystatin C could protect the brain from amyloid-induced toxicity and may have therapetic implications for AD.
TextSentencer_T129 22124-22359 Sentence denotes 56 However, there are opposing results demonstrating neuronal cell death upon injecting cystatin C into the brain of AD mouse model, 123 showing that cystatin C triggers Aβ accumulation by inhibiting cathepsin B-induced Aβ degradation.
TextSentencer_T129 22124-22359 Sentence denotes 56 However, there are opposing results demonstrating neuronal cell death upon injecting cystatin C into the brain of AD mouse model, 123 showing that cystatin C triggers Aβ accumulation by inhibiting cathepsin B-induced Aβ degradation.
TextSentencer_T130 22360-22773 Sentence denotes 124 Cystatin C may have an important role in brain injuries as its enhanced expression has been observed in response to different types of insults to the brain, such as ischemia and epilepsy. [125] [126] [127] Regarding constant serum concentrations of cystatin C it is a suitable marker for glomerular filtration rate (GFR) and kidney function and thus has a possible application as a replacement for creatinine.
TextSentencer_T130 22360-22773 Sentence denotes 124 Cystatin C may have an important role in brain injuries as its enhanced expression has been observed in response to different types of insults to the brain, such as ischemia and epilepsy. [125] [126] [127] Regarding constant serum concentrations of cystatin C it is a suitable marker for glomerular filtration rate (GFR) and kidney function and thus has a possible application as a replacement for creatinine.
TextSentencer_T131 22774-22961 Sentence denotes 128, 129 Studies on the sensitivity and specificity of cystatin C for detecting impaired GFR strongly suggest it to be superior diagnostic marker to creatinine for detecting impaired GFR.
TextSentencer_T131 22774-22961 Sentence denotes 128, 129 Studies on the sensitivity and specificity of cystatin C for detecting impaired GFR strongly suggest it to be superior diagnostic marker to creatinine for detecting impaired GFR.
TextSentencer_T132 22962-23167 Sentence denotes 130 However, caution is necessary in case of patients with malignancy or other diseases with increased activity of cyteine proteases which exhibit increased cystatin C levels irrelevant to kidney function.
TextSentencer_T132 22962-23167 Sentence denotes 130 However, caution is necessary in case of patients with malignancy or other diseases with increased activity of cyteine proteases which exhibit increased cystatin C levels irrelevant to kidney function.
TextSentencer_T133 23168-23347 Sentence denotes 131 It has been suggested that disturbance of the cystatin E/M-cathepsin pathway could contribute to dysregulated skin barrier function as observed in the inflammatory dermatoses.
TextSentencer_T133 23168-23347 Sentence denotes 131 It has been suggested that disturbance of the cystatin E/M-cathepsin pathway could contribute to dysregulated skin barrier function as observed in the inflammatory dermatoses.
TextSentencer_T134 23348-23523 Sentence denotes Atopic dermatitis and psoriasis are two common chronic inflammatory skin diseases in which the expression of many genes and the formation of the epidermal barrier are altered.
TextSentencer_T134 23348-23523 Sentence denotes Atopic dermatitis and psoriasis are two common chronic inflammatory skin diseases in which the expression of many genes and the formation of the epidermal barrier are altered.
TextSentencer_T135 23524-23687 Sentence denotes Recent genetic studies have revealed that abnormalities in epithelium-expressed genes are an important etiological factor. [132] [133] [134] The study Cheng et al.
TextSentencer_T135 23524-23687 Sentence denotes Recent genetic studies have revealed that abnormalities in epithelium-expressed genes are an important etiological factor. [132] [133] [134] The study Cheng et al.
TextSentencer_T136 23688-23907 Sentence denotes 86 have shown decreased mRNA and protein expression levels of cystatin E/M and cathepsin V in the inflamed skin during atopic dermatitis and psoriasis, which suggests their prominent role in these inflammatory diseases.
TextSentencer_T136 23688-23907 Sentence denotes 86 have shown decreased mRNA and protein expression levels of cystatin E/M and cathepsin V in the inflamed skin during atopic dermatitis and psoriasis, which suggests their prominent role in these inflammatory diseases.
TextSentencer_T137 23908-23985 Sentence denotes Expression of cystatin F has been associated to some pathological conditions.
TextSentencer_T137 23908-23985 Sentence denotes Expression of cystatin F has been associated to some pathological conditions.
TextSentencer_T138 23986-24200 Sentence denotes It was found to be massively expressed in the microglia, mono-cyte/macrophage cells in the cental nervous system, only during acute demyelination and ceased in chronic phase, in which remyelinating ability is lost.
TextSentencer_T138 23986-24200 Sentence denotes It was found to be massively expressed in the microglia, mono-cyte/macrophage cells in the cental nervous system, only during acute demyelination and ceased in chronic phase, in which remyelinating ability is lost.
TextSentencer_T139 24201-24481 Sentence denotes Expression of cystatin F thus indicates the occurrence of ongoing demyelination/remyelination during multiple sclerosis and might serve as a good indicator for this process, however, it is not clear whether changes in cystatin F levels result from or cause arrested remyelination.
TextSentencer_T139 24201-24481 Sentence denotes Expression of cystatin F thus indicates the occurrence of ongoing demyelination/remyelination during multiple sclerosis and might serve as a good indicator for this process, however, it is not clear whether changes in cystatin F levels result from or cause arrested remyelination.
TextSentencer_T140 24482-24794 Sentence denotes 135 The level of cystatin F mRNA was increased in the granulocytes of the patients with polycythemia vera, a myeloproliferative disorder characterized by an increased proliferation of cells of myeloid lineages 136 and downregulated in peripheral blood mononuclear cells of patients with chronic fatigue syndrome.
TextSentencer_T140 24482-24794 Sentence denotes 135 The level of cystatin F mRNA was increased in the granulocytes of the patients with polycythemia vera, a myeloproliferative disorder characterized by an increased proliferation of cells of myeloid lineages 136 and downregulated in peripheral blood mononuclear cells of patients with chronic fatigue syndrome.
TextSentencer_T141 24795-24891 Sentence denotes 137 Higher expression of the inhibitor correlates with inflammatory processes of lung disorders.
TextSentencer_T141 24795-24891 Sentence denotes 137 Higher expression of the inhibitor correlates with inflammatory processes of lung disorders.
TextSentencer_T142 24892-25004 Sentence denotes 138 Given the high concentrations of cystatins in saliva and tears it is likely to have a more specialized role.
TextSentencer_T142 24892-25004 Sentence denotes 138 Given the high concentrations of cystatins in saliva and tears it is likely to have a more specialized role.
TextSentencer_T143 25005-25108 Sentence denotes Their concentrations in saliva of subjects with periodontitis were found to be significantly increased.
TextSentencer_T143 25005-25108 Sentence denotes Their concentrations in saliva of subjects with periodontitis were found to be significantly increased.
TextSentencer_T144 25109-25409 Sentence denotes 139 Cystatin SN was found to inhibit the human cathepsins B, H and L and cystatin SA was found to inhibit human lysosomal cathepsin L, the proteases that are involved in periodontal tissue destruction suggesting the involvment of salivary cystatins SA and SN in the control of the proteolytic events.
TextSentencer_T144 25109-25409 Sentence denotes 139 Cystatin SN was found to inhibit the human cathepsins B, H and L and cystatin SA was found to inhibit human lysosomal cathepsin L, the proteases that are involved in periodontal tissue destruction suggesting the involvment of salivary cystatins SA and SN in the control of the proteolytic events.
TextSentencer_T145 25410-25664 Sentence denotes 108 However, weak inhibitory activity against cathepsins B, H, L and potent inhibition of cysteine proteases from parasitic organisms cleary indicate that salivary cystatins help to control the oral microorganisms rather than prevent periodotal diseases.
TextSentencer_T145 25410-25664 Sentence denotes 108 However, weak inhibitory activity against cathepsins B, H, L and potent inhibition of cysteine proteases from parasitic organisms cleary indicate that salivary cystatins help to control the oral microorganisms rather than prevent periodotal diseases.
TextSentencer_T146 25665-25793 Sentence denotes There are an accumulating number of studies showing that cystatins are implicated in the progression of various types of cancer.
TextSentencer_T146 25665-25793 Sentence denotes There are an accumulating number of studies showing that cystatins are implicated in the progression of various types of cancer.
TextSentencer_T147 25794-25926 Sentence denotes In general, their localization and regulation of tumor associated proteolytic activity can be recognized by two distinct mechanisms.
TextSentencer_T147 25794-25926 Sentence denotes In general, their localization and regulation of tumor associated proteolytic activity can be recognized by two distinct mechanisms.
TextSentencer_T148 25927-26100 Sentence denotes Type I cystatins, stefins A and B are up-regulated in tumor tissue and, up to a certain level could counter-balance the over-expressed tumor-associated proteolytic activity.
TextSentencer_T148 25927-26100 Sentence denotes Type I cystatins, stefins A and B are up-regulated in tumor tissue and, up to a certain level could counter-balance the over-expressed tumor-associated proteolytic activity.
TextSentencer_T149 26101-26246 Sentence denotes Their function as tumor suppressors is supported by survival analysis, which associated their high levels with better outcome of cancer patients.
TextSentencer_T149 26101-26246 Sentence denotes Their function as tumor suppressors is supported by survival analysis, which associated their high levels with better outcome of cancer patients.
TextSentencer_T150 26247-26398 Sentence denotes For example, in brain tumors, increase of cathepsin B expression and lower levels of its inhibitor stefin A were associated with tumor malignancy 140 .
TextSentencer_T150 26247-26398 Sentence denotes For example, in brain tumors, increase of cathepsin B expression and lower levels of its inhibitor stefin A were associated with tumor malignancy 140 .
TextSentencer_T151 26399-26505 Sentence denotes On the other hand, type II cystatins, at least cystatins C and E/M are generally down-regulated in tumors.
TextSentencer_T151 26399-26505 Sentence denotes On the other hand, type II cystatins, at least cystatins C and E/M are generally down-regulated in tumors.
TextSentencer_T152 26506-26636 Sentence denotes Although their role remains protective, their lower levels could allow a surplus of harmful tumor associated proteolytic activity.
TextSentencer_T152 26506-26636 Sentence denotes Although their role remains protective, their lower levels could allow a surplus of harmful tumor associated proteolytic activity.
TextSentencer_T153 26637-26862 Sentence denotes Outside the cells, higher levels of type II cystatins may impair extracellular activity of cysteine proteases, associated directly or indirectly with the degradation of ECM and resulting in tumor cell invasion and metastasis.
TextSentencer_T153 26637-26862 Sentence denotes Outside the cells, higher levels of type II cystatins may impair extracellular activity of cysteine proteases, associated directly or indirectly with the degradation of ECM and resulting in tumor cell invasion and metastasis.
TextSentencer_T154 26863-27060 Sentence denotes However, higher levels of cystatins in body fluids have been associated with poor prognosis in cancer patients supporting their role in regulation of proteases involved in the regression of tumors.
TextSentencer_T154 26863-27060 Sentence denotes However, higher levels of cystatins in body fluids have been associated with poor prognosis in cancer patients supporting their role in regulation of proteases involved in the regression of tumors.
TextSentencer_T155 27061-27251 Sentence denotes In melanoma and colorectal cancer, increased extracellular levels of cystatin C as well as stefins correlated significantly with high risk of adverse outcome in cancer patients ( Figure 2 ).
TextSentencer_T155 27061-27251 Sentence denotes In melanoma and colorectal cancer, increased extracellular levels of cystatin C as well as stefins correlated significantly with high risk of adverse outcome in cancer patients ( Figure 2 ).
TextSentencer_T156 27252-27430 Sentence denotes Cathepsin B/cystatin C complex was also found to be less abundant in sera of patients with tumors suggesting an imbalance between the enzyme and its inhibitor in cancer patients.
TextSentencer_T156 27252-27430 Sentence denotes Cathepsin B/cystatin C complex was also found to be less abundant in sera of patients with tumors suggesting an imbalance between the enzyme and its inhibitor in cancer patients.
TextSentencer_T157 27431-27590 Sentence denotes 141 Animals with excluded expression of type I or type II cystatins experience better outcome with regard to tumor growth and metastasis as the wild type ones.
TextSentencer_T157 27431-27590 Sentence denotes 141 Animals with excluded expression of type I or type II cystatins experience better outcome with regard to tumor growth and metastasis as the wild type ones.
TextSentencer_T158 27591-27806 Sentence denotes These contradictive results can be explained by the fact that type II cystatins are involved also in processes resulting in tumor regression such as anti-tumor immune response, apoptosis, cell migration and seeding.
TextSentencer_T158 27591-27806 Sentence denotes These contradictive results can be explained by the fact that type II cystatins are involved also in processes resulting in tumor regression such as anti-tumor immune response, apoptosis, cell migration and seeding.
TextSentencer_T159 27807-28192 Sentence denotes 9 In particular, the role of cysteine proteases is very important for proper maturation of antigen presenting cells, antigen processing and the presentation to T cells, therefore, the enhanced inhibition may affect the activation of naive T cells by tumor associated antigens and impair T cell dependent anti-tumor immune response, known to be effective for eradication of tumor cells.
TextSentencer_T159 27807-28192 Sentence denotes 9 In particular, the role of cysteine proteases is very important for proper maturation of antigen presenting cells, antigen processing and the presentation to T cells, therefore, the enhanced inhibition may affect the activation of naive T cells by tumor associated antigens and impair T cell dependent anti-tumor immune response, known to be effective for eradication of tumor cells.
TextSentencer_T160 28193-28400 Sentence denotes Higher levels of cystatins may affect also the innate immunity, as mentioned above, increased levels of cystatin F inactivate cathepsin C and thus impair activation of granzymes and cytotoxicity of NK cells.
TextSentencer_T160 28193-28400 Sentence denotes Higher levels of cystatins may affect also the innate immunity, as mentioned above, increased levels of cystatin F inactivate cathepsin C and thus impair activation of granzymes and cytotoxicity of NK cells.
TextSentencer_T161 28401-28665 Sentence denotes 75, 142 On the other hand, patients with higher local levels of stefins A and B in non-small cell lung tissue than in control lung tissue exhibited a better survival probability implying on their ability to counteract harmful tumor-associated proteolytic activity.
TextSentencer_T161 28401-28665 Sentence denotes 75, 142 On the other hand, patients with higher local levels of stefins A and B in non-small cell lung tissue than in control lung tissue exhibited a better survival probability implying on their ability to counteract harmful tumor-associated proteolytic activity.
TextSentencer_T162 28666-28764 Sentence denotes 143 Also, the overexpression of cystatin C in tumor cells inhibited melanoma metastasis formation.
TextSentencer_T162 28666-28764 Sentence denotes 143 Also, the overexpression of cystatin C in tumor cells inhibited melanoma metastasis formation.
TextSentencer_T163 28765-29088 Sentence denotes 144 Thus, besides the concentration, cell and tissue localization of cystatins could make a critical switch between harmless and harmful and their application as anti-cancer agents has to be considered with caution and should be directed specifically to cysteine proteases which promote specific stage of tumor progression.
TextSentencer_T163 28765-29088 Sentence denotes 144 Thus, besides the concentration, cell and tissue localization of cystatins could make a critical switch between harmless and harmful and their application as anti-cancer agents has to be considered with caution and should be directed specifically to cysteine proteases which promote specific stage of tumor progression.
TextSentencer_T164 29089-29214 Sentence denotes For instance, the expression and the role of cystatin E/M in tumorigenesis may differes depending on the stage of the cancer.
TextSentencer_T164 29089-29214 Sentence denotes For instance, the expression and the role of cystatin E/M in tumorigenesis may differes depending on the stage of the cancer.
TextSentencer_T165 29215-29502 Sentence denotes Since it was initially identified as a downregulated mRNA in metastatic breast tumor cells compared to normal and primary breast tumor cells 82 , it is likely that the loss of the expression of cystatin E/M is associated with the progression of a primary tumor to a metastatic phenotype.
TextSentencer_T165 29215-29502 Sentence denotes Since it was initially identified as a downregulated mRNA in metastatic breast tumor cells compared to normal and primary breast tumor cells 82 , it is likely that the loss of the expression of cystatin E/M is associated with the progression of a primary tumor to a metastatic phenotype.
TextSentencer_T166 29503-29833 Sentence denotes Furthermore, scid mice orthotopically implanted with cystatin E/M-expressing MDA-MB-435S breast cancer cells show significantly delayed primary tumor growth compared to controls, the incidence of metastasis, however, appeared to be unaltered, confirming that cystatin E/M suppressed tumor cell proliferation at the secondary site.
TextSentencer_T166 29503-29833 Sentence denotes Furthermore, scid mice orthotopically implanted with cystatin E/M-expressing MDA-MB-435S breast cancer cells show significantly delayed primary tumor growth compared to controls, the incidence of metastasis, however, appeared to be unaltered, confirming that cystatin E/M suppressed tumor cell proliferation at the secondary site.
TextSentencer_T167 29834-29973 Sentence denotes 145 Higher level of cystatin F mRNA in the colorectal cancer tissue correlated both with liver metastasis and with worse patient prognosis.
TextSentencer_T167 29834-29973 Sentence denotes 145 Higher level of cystatin F mRNA in the colorectal cancer tissue correlated both with liver metastasis and with worse patient prognosis.
TextSentencer_T168 29974-30223 Sentence denotes 146 Therefore, it is possible that a determination of the cystatin F mRNA expression may help in the identification of patients at high risk for metastasis, and these patients could thereby benefit from careful examinations and extensive treatments.
TextSentencer_T168 29974-30223 Sentence denotes 146 Therefore, it is possible that a determination of the cystatin F mRNA expression may help in the identification of patients at high risk for metastasis, and these patients could thereby benefit from careful examinations and extensive treatments.
TextSentencer_T169 30224-30454 Sentence denotes The pathways by which cystatins modulate immune response unrelated to their function of cysteine protease inhibitors, cannot be excluded, as shown for cystatins of filarial nematodes 147 , chicken cystatin 148, 149 and cystatin C.
TextSentencer_T169 30224-30454 Sentence denotes The pathways by which cystatins modulate immune response unrelated to their function of cysteine protease inhibitors, cannot be excluded, as shown for cystatins of filarial nematodes 147 , chicken cystatin 148, 149 and cystatin C.
TextSentencer_T170 30455-30664 Sentence denotes 150 The latter has been shown to antagonize TGF-β binding to the cell surface receptors of normal and cancer cells by interacting physically with the TGF-β type II receptor and abrogating the binding of TGF-β.
TextSentencer_T170 30455-30664 Sentence denotes 150 The latter has been shown to antagonize TGF-β binding to the cell surface receptors of normal and cancer cells by interacting physically with the TGF-β type II receptor and abrogating the binding of TGF-β.
TextSentencer_T171 30665-30768 Sentence denotes TGF-β is a multifunctional cytokine endowed with both tumor-suppressing and tumor-promoting activities.
TextSentencer_T171 30665-30768 Sentence denotes TGF-β is a multifunctional cytokine endowed with both tumor-suppressing and tumor-promoting activities.
TextSentencer_T172 30769-30969 Sentence denotes In normal cells TGF-β inhibits proliferation and induce apoptosis, however during the transformation to cancer cell it becomes a trophic factor for the transformed cells promoting their proliferation.
TextSentencer_T172 30769-30969 Sentence denotes In normal cells TGF-β inhibits proliferation and induce apoptosis, however during the transformation to cancer cell it becomes a trophic factor for the transformed cells promoting their proliferation.
TextSentencer_T173 30970-31236 Sentence denotes 151, 152 Interestingly, down regulation of tumorogenesis through a similar mechanism has been shown also for a family-3 cystatin (AHSG) which inhibits colon carcinogenesis by suppressing TGF-β signal transduction by blocking TGF-β1 binding to cell surface receptors.
TextSentencer_T173 30970-31236 Sentence denotes 151, 152 Interestingly, down regulation of tumorogenesis through a similar mechanism has been shown also for a family-3 cystatin (AHSG) which inhibits colon carcinogenesis by suppressing TGF-β signal transduction by blocking TGF-β1 binding to cell surface receptors.
TextSentencer_T174 31237-31452 Sentence denotes 153 There is an evidence indicating that cystatin E/M is a tumor suppressor factor important in breast and brain malignancy reducing tumor cell proliferation, its expression is markedly decreased in carcinoma cells.
TextSentencer_T174 31237-31452 Sentence denotes 153 There is an evidence indicating that cystatin E/M is a tumor suppressor factor important in breast and brain malignancy reducing tumor cell proliferation, its expression is markedly decreased in carcinoma cells.
TextSentencer_T175 31453-31498 Sentence denotes 87, 88, 145, 154 In the study Shridhar et al.
TextSentencer_T175 31453-31498 Sentence denotes 87, 88, 145, 154 In the study Shridhar et al.
TextSentencer_T176 31499-31712 Sentence denotes 155 , the effects of cystatin E/M expression on malignant properties were examined on human breast carcinoma MDA-MB-435S cells, which are highly tumorigenic and metastatic and normally do not express cystatin E/M.
TextSentencer_T176 31499-31712 Sentence denotes 155 , the effects of cystatin E/M expression on malignant properties were examined on human breast carcinoma MDA-MB-435S cells, which are highly tumorigenic and metastatic and normally do not express cystatin E/M.
TextSentencer_T177 31713-31898 Sentence denotes The constitutive cystatin E/M expression in transfected cells resulted in a significant reduction of cell proliferation, migration, Matrigel invasion, and adhesion to endothelial cells.
TextSentencer_T177 31713-31898 Sentence denotes The constitutive cystatin E/M expression in transfected cells resulted in a significant reduction of cell proliferation, migration, Matrigel invasion, and adhesion to endothelial cells.
TextSentencer_T178 31899-32074 Sentence denotes Cell migration and matrix invasion appeared to be controlled by the lysosomal cysteine proteases, as both recombinant cystatin E/M and E-64 were able to block these processes.
TextSentencer_T178 31899-32074 Sentence denotes Cell migration and matrix invasion appeared to be controlled by the lysosomal cysteine proteases, as both recombinant cystatin E/M and E-64 were able to block these processes.
TextSentencer_T179 32075-32238 Sentence denotes In contrast, reduction of cell proliferation and adhesion to an endothelial cell monolayer were both independent of the inhibition of lysosomal cysteine proteases.
TextSentencer_T179 32075-32238 Sentence denotes In contrast, reduction of cell proliferation and adhesion to an endothelial cell monolayer were both independent of the inhibition of lysosomal cysteine proteases.
TextSentencer_T180 32239-32403 Sentence denotes Cystatin E/M could thus act through various mehanisms, besides inhibition of cysteine proteases also by inhibition of legumain and modulation of gene transcription.
TextSentencer_T180 32239-32403 Sentence denotes Cystatin E/M could thus act through various mehanisms, besides inhibition of cysteine proteases also by inhibition of legumain and modulation of gene transcription.
TextSentencer_T181 32404-32759 Sentence denotes The latter is confirmed by the fact, that cystatin E/M expression in MDA-MB-435S cells significantly changed the expression of extracellular matrix components, cytokines, kinases, and phosphatases, as well as several key transcription factors, including downregulation of autotaxin, a signaling molecule that has been linked to breast cancer invasiveness.
TextSentencer_T181 32404-32759 Sentence denotes The latter is confirmed by the fact, that cystatin E/M expression in MDA-MB-435S cells significantly changed the expression of extracellular matrix components, cytokines, kinases, and phosphatases, as well as several key transcription factors, including downregulation of autotaxin, a signaling molecule that has been linked to breast cancer invasiveness.
TextSentencer_T182 32760-32923 Sentence denotes 156 Furthermore, epigenetic studies reported DNA methylation-dependent silencing of the cystatin E/M gene in breast cancer cell lines and in primary breast tumors.
TextSentencer_T182 32760-32923 Sentence denotes 156 Furthermore, epigenetic studies reported DNA methylation-dependent silencing of the cystatin E/M gene in breast cancer cell lines and in primary breast tumors.
TextSentencer_T183 32924-33144 Sentence denotes Hypermethylation was significantly associated with gene silencing and loss of cystatin E/M protein expression, whereas enhanced gene expression was measured in breast cancer cells cultured on the DNA demethylating agent.
TextSentencer_T183 32924-33144 Sentence denotes Hypermethylation was significantly associated with gene silencing and loss of cystatin E/M protein expression, whereas enhanced gene expression was measured in breast cancer cells cultured on the DNA demethylating agent.
TextSentencer_T184 33145-33266 Sentence denotes 154, 157, 158 Collectively these data suggest that cystatin E/M could act as a tumor supressor through various mehanisms.
TextSentencer_T184 33145-33266 Sentence denotes 154, 157, 158 Collectively these data suggest that cystatin E/M could act as a tumor supressor through various mehanisms.
TextSentencer_T185 33268-33356 Sentence denotes In conclusion, cystatins are involved in a number of normal and pathological conditions.
TextSentencer_T185 33268-33356 Sentence denotes In conclusion, cystatins are involved in a number of normal and pathological conditions.
TextSentencer_T186 33357-33517 Sentence denotes They exert several immunomodulatory functions by controlling the activity of cysteine proteases or by other mechanisms not related to their inhibitory function.
TextSentencer_T186 33357-33517 Sentence denotes They exert several immunomodulatory functions by controlling the activity of cysteine proteases or by other mechanisms not related to their inhibitory function.
TextSentencer_T187 33518-33767 Sentence denotes They may contribute to the proteolytic processing of progranzymes and other substrates, major histocompatibility complex class II antigen presentation, maturation of dendritic cells, modulation of integrin function and formation of the skin barrier.
TextSentencer_T187 33518-33767 Sentence denotes They may contribute to the proteolytic processing of progranzymes and other substrates, major histocompatibility complex class II antigen presentation, maturation of dendritic cells, modulation of integrin function and formation of the skin barrier.
TextSentencer_T188 33768-33972 Sentence denotes It has become evident that disturbances in expression and localization of cystatins may be implicated in several pathological processes, such as inflammatory skin diseases and neurodegenerative disorders.
TextSentencer_T188 33768-33972 Sentence denotes It has become evident that disturbances in expression and localization of cystatins may be implicated in several pathological processes, such as inflammatory skin diseases and neurodegenerative disorders.
TextSentencer_T189 33973-34092 Sentence denotes In particular for stefin B and cystatin C, association with am-yloid-beta in Alzheimer's disease has been demonstrated.
TextSentencer_T189 33973-34092 Sentence denotes In particular for stefin B and cystatin C, association with am-yloid-beta in Alzheimer's disease has been demonstrated.
TextSentencer_T190 34093-34374 Sentence denotes In cancer, inhibitory effect of cystatins could beneficially counteract tumor-associated proteolytic activity or, could also be harmful when impairing the functions in cysteine cathepsins in anti-tumor immune response and is strongly depended on their cell and tissue localization.
TextSentencer_T190 34093-34374 Sentence denotes In cancer, inhibitory effect of cystatins could beneficially counteract tumor-associated proteolytic activity or, could also be harmful when impairing the functions in cysteine cathepsins in anti-tumor immune response and is strongly depended on their cell and tissue localization.