PMC:7271924 / 4318-8571 JSONTXT 14 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T31 0-23 Sentence denotes Discovery and Structure
T32 24-212 Sentence denotes Human LF is a cationic glycosylated protein consisting of 691 amino acids (9) folded into two globular lobes (80 kDa bi-lobal glycoprotein) (10), that are connected by an α-helix (11, 12).
T33 213-253 Sentence denotes Bovine LF contains 689 amino acids (13).
T34 254-427 Sentence denotes LF was first discovered and isolated from bovine milk in 1939 (14), and is a member of the transferrin family (60% amino acid sequence identity with serum transferrin) (11).
T35 428-652 Sentence denotes LF and transferrin have similar amino acid compositions, secondary structures (including their disulphide linkages), and tertiary structures, although they differ in terms of biological functions (11, 15, 16) (see Figure 2).
T36 653-811 Sentence denotes There are also three different isoforms: LF-α is the iron-binding isoform, while LF- β and LF-g both have ribonuclease activity but do not bind iron (11, 17).
T37 812-906 Sentence denotes When it is iron-rich it is referred to hololactoferrin and when iron-free apolactoferrin (18).
T38 907-1144 Sentence denotes The tertiary structures of the two forms are significantly different: apolactoferrin is characterized by an open conformation of the N-lobe and a closed conformation of the C-lobe, while both lobes are closed in the hololactoferrin (18).
T39 1145-1333 Sentence denotes Human LF and bovine LF possess high sequence homology and have very similar antibacterial, antifungal, antiviral, antiparasitic, anti-inflammatory, and immunomodulatory activities (19–21).
T40 1334-1442 Sentence denotes Consequently, it is common to give the bovine form rather than say a recombinant human form as a supplement.
T41 1443-1614 Sentence denotes Bovine LF is also deemed a “generally recognized as safe” substance by the Food and Drug Administration (FDA, USA), and is commercially available in large quantities (19).
T42 1615-1747 Sentence denotes Figure 2 Crystal structures of bovine lactoferrin (PDB code = 1BLF), human lactoferrin (1B0L), and rabbit serum transferrin (1JNF).
T43 1748-1772 Sentence denotes Adapted from Vogel (10).
T44 1773-1829 Sentence denotes Pink spheres represent ferric iron (Fe3+) binding sites.
T45 1830-2033 Sentence denotes Due to its similarities to transferrin, which is the main iron transporting molecule in serum (22, 23), α-LF possesses iron binding capabilities (24, 25), and it can chelate two ferric irons (Fe3+) (26).
T46 2034-2175 Sentence denotes LF binds one ferric iron atom in each of its two lobes; however, an important attribute is that it does not release its iron, even at pH 3.5.
T47 2176-2299 Sentence denotes This is of importance as this property assures iron sequestration in infected tissues where the pH is commonly acidic (27).
T48 2300-2474 Sentence denotes In the context of its iron-binding capabilities, it means that when it binds ferric and siderophore-bound iron, it limits the availability of essential iron to microbes (27).
T49 2475-2668 Sentence denotes In healthy individuals, iron is largely intracellular and sequestered within ferritin or as a co-factor of cytochromes and FeS proteins, and as haem complexed to hemoglobin within erythrocytes.
T50 2669-2727 Sentence denotes Circulating iron is rapidly bound by transferrin (28, 29).
T51 2728-2880 Sentence denotes When erythrocytes lyse and hemoglobin or haem is released into the circulation, their hemoglobin is captured by haptoglobin, and haem by hemopexin (30).
T52 2881-3067 Sentence denotes Here, circulating serum ferroxidase ceruloplasmin is of importance, as LF can bind to ceruloplasmin, such that a direct transfer of ferric iron between the two proteins is possible (31).
T53 3068-3258 Sentence denotes A direct transfer of ferric iron from ceruloplasmin to lactoferrin prevents both the formation of potentially toxic hydroxyl radicals (32) and the utilization of iron by pathogenic bacteria.
T54 3259-3460 Sentence denotes LF is therefore an important player in preventing bacteria from acquiring and sequestering iron, which [with the possible exception of Borrelia burgdorferi (33)]; they require for growth and virulence.
T55 3461-3575 Sentence denotes LF also acts as biomarker, as it is commonly upregulated when the host is suffering from various kinds of disease.
T56 3576-3612 Sentence denotes See Table 1 for selected references.
T57 3613-3732 Sentence denotes Table 1 Lactoferrin as a major player in host defense and iron binding, and its use as biomarker for various diseases.
T58 3733-3760 Sentence denotes Area of action References
T59 3761-3805 Sentence denotes Protecting neonates via breast milk (34–41)
T60 3806-3924 Sentence denotes LF in cervicovaginal mucosa and female reproductive tract; antibacterial, antifungal antiparasitic, antiviral (42–45)
T61 3925-3952 Sentence denotes LF in the airways (46, 47)
T62 3953-4009 Sentence denotes Mucosal surfaces, allergen-induces skin infections (48)
T63 4010-4062 Sentence denotes Neutrophil extracellular trap (NET) production (49)
T64 4063-4128 Sentence denotes Saliva and its antimicrobial activities and iron binding (50–52)
T65 4129-4183 Sentence denotes Saliva as biomarker for neurological diseases (53–55)
T66 4184-4253 Sentence denotes Saliva as biomarker for periodontal disease and oral dryness (56–59)