LitCovid-sentences  

PMC:7271924 / 13792-25088 JSONTXT 15 Projects

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Id Subject Object Predicate Lexical cue
T108 0-49 Sentence denotes Lactoferrin: an Important Element in Host Defense
T109 51-78 Sentence denotes Neutrophils and Lactoferrin
T110 79-165 Sentence denotes LF plays an important role in host defense, upon its release from the neutrophil (26).
T111 166-309 Sentence denotes LF also enhances natural killer cell activity in immune defense (135) and can restrict the entry of the virus into host cells during infection.
T112 310-450 Sentence denotes As part of the host's inflammatory response, leucocytes, including neutrophils, release LF from their granules, where it is normally stored.
T113 451-607 Sentence denotes Activated neutrophils also release chromatin fibers, known as neutrophil extracellular traps (NETs), which trap and kill, amongst others, bacteria (1, 136).
T114 608-684 Sentence denotes These NETs likewise modulate both acute and chronic inflammation (137, 138).
T115 685-808 Sentence denotes NETs are also found in various autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus (139, 140).
T116 809-875 Sentence denotes Interestingly, 106 human neutrophils can release 15 μg of LF (26).
T117 876-1017 Sentence denotes In addition to DNA and histones, NET fibers contain extranuclear proteins and proteins such as elastase, myeloperoxidase (MPO), and LF (141).
T118 1018-1161 Sentence denotes LF may also serve as an intrinsic inhibitor of NETs release into the circulation, and may therefore be central in controlling NETs release (1).
T119 1162-1175 Sentence denotes See Figure 3.
T120 1176-1490 Sentence denotes Figure 3 Bacterial binding to various receptors, e.g., Toll-like receptors 2 and 4 (TLR2 and 4), as well as complement receptors, leads to protein arginine deiminase 4 (PAD4) activation, followed by chromatin decondensation, hypercitrullination of histones 3 and 4 in the nucleus, and nuclear membrane disruption.
T121 1491-1525 Sentence denotes Granules also release lactoferrin.
T122 1526-1652 Sentence denotes Neutrophil Extracellular Traps (NETs) and their protein constituents (including lactoferrin) are released from the neutrophil.
T123 1653-1711 Sentence denotes Adapted from Jorch and Kubes (142) and Law and Gray (143).
T124 1712-1758 Sentence denotes Bacteria are expelled and trapped in the NETs.
T125 1759-1815 Sentence denotes Diagram created with BioRender (https://biorender.com/).
T126 1817-1841 Sentence denotes Bacteria and Lactoferrin
T127 1842-2033 Sentence denotes One of the most well-known characteristics of LF is that it is antibacterial (19, 144–148), antiviral (99, 149–151), antifungal (152–154), anti-inflammatory (26), and anti-carcinogenic (155).
T128 2034-2132 Sentence denotes Its ability to of limit iron availability to microbes is one of its crucial amicrobial properties.
T129 2133-2204 Sentence denotes Bacteria have, however, developed various ways to sequester iron (156).
T130 2205-2376 Sentence denotes Figure 4 shows how bacteria acquire iron through receptor-mediated recognition of transferrin, hemopexin, hemoglobin, or hemoglobin-haptoglobin complexes and also LF (30).
T131 2377-2532 Sentence denotes As well as binding it directly from the environment, bacterial siderophores can obtain iron by removing it from transferrin, lactoferrin, or ferritin (32).
T132 2533-2621 Sentence denotes These siderophore-iron complexes are then recognized by receptors on the bacterium (30).
T133 2622-2860 Sentence denotes Host innate immune functions are supported by the circulating protein, siderocalin, also known as Neutrophil gelatinase-associated lipocalin (NGAL), lipocalin2 or Lcn2 as it inhibits siderophore-mediated iron acquisition and release (30).
T134 2861-2931 Sentence denotes Figure 4 Ways by which bacteria acquire iron [adapted from (19, 30)].
T135 2932-3026 Sentence denotes Transferrin receptor, lactoferrin receptor, hemophore (Hp), hemophore receptor, and hemopexin.
T136 3027-3126 Sentence denotes Siderophores remove iron from lactoferrin, ferritin and transferrin, and also from the environment.
T137 3127-3209 Sentence denotes Stealth siderophores are modified in such a way as to prevent siderocalin binding.
T138 3210-3306 Sentence denotes A primary bacterial defense against siderocalin involves the production of stealth siderophores.
T139 3307-3352 Sentence denotes Modified from Rosa et al. and Skaar (19, 30).
T140 3353-3409 Sentence denotes Diagram created with BioRender (https://biorender.com/).
T141 3410-3576 Sentence denotes Although LF has various means to counteract bacteria as part of its immune function (131), it is also capable of being hijacked to benefit the activities of bacteria.
T142 3577-3655 Sentence denotes Thus, bacteria can also exploit LF by removing its bound ferric iron (19, 30).
T143 3656-3975 Sentence denotes This process involves (1) synthesis of high-affinity ferric ion chelators by bacteria, (2) iron acquisition through LF or transferrin binding, mediated by bacterial-specific surface bacterial receptors, (3) or iron acquisition through bacterial reductases, which are able to reduce ferric to ferrous ions (19, 144–148).
T144 3976-4160 Sentence denotes Several Gram-negative pathogens including members of the genera Neisseria and Moraxella have evolved two-component systems that can extract iron from the host LF and transferrin (157).
T145 4161-4234 Sentence denotes N. meningitidis is a principal cause of bacterial meningitis in children.
T146 4235-4481 Sentence denotes While the majority of pathogenic bacteria employ siderophores to chelate and scavenge iron (158), Neisseria has evolved a series of protein transporters that directly hijack iron sequestered in host transferrin, lactoferrin, and hemoglobin (159).
T147 4482-4784 Sentence denotes The system consists of a membrane-bound transporter that extracts and transports iron across the outer membrane (TbpA for transferrin and LbpA for lactoferrin), and a lipoprotein that delivers iron-loaded lactoferrin/transferrin to the transporter (TbpB for transferrin and LbpB for lactoferrin) (157).
T148 4785-4874 Sentence denotes LbpB binds the N-lobe of lactoferrin, whereas TbpB binds the C-lobe of transferrin (157).
T149 4875-5087 Sentence denotes However, more than 90% of LF in human milk is in the form of apolactoferrin (160), which competes with siderophilic bacteria for ferric iron, and disrupts the proliferation of these microbial and other pathogens.
T150 5088-5174 Sentence denotes Similarly LF supplements may play an important role to counteract bacterial processes.
T151 5175-5291 Sentence denotes LF is consequently a significant element of host defense (19), and its levels may vary in health and during disease.
T152 5292-5374 Sentence denotes It is hence known to be a modulator of innate and adaptive immune responses (161).
T153 5376-5399 Sentence denotes Viruses and Lactoferrin
T154 5400-5520 Sentence denotes LF has strong antiviral activity against a broad spectrum of both naked and enveloped DNA and RNA viruses (99, 149–151).
T155 5521-5711 Sentence denotes LF inhibits the entry of viral particles into host cells, either by direct attachment to the viral particles or by blocking their cellular receptors (discussed in previous paragraphs) (149).
T156 5712-5898 Sentence denotes Some of the viruses that LF prevents from entering host cells e.g., Herpes simplex virus (162), human papillomavirus (163), human immunodeficiency virus (HIV) (164), and rotavirus (165).
T157 5899-6037 Sentence denotes These viruses typically utilize common molecules on the cell membrane to facilitate their invasion into cells, including HSPGs (Figure 1).
T158 6038-6171 Sentence denotes HSPGs provide the first anchoring sites on the host cell surface, and help the virus make primary contact with these cells (99, 162).
T159 6172-6270 Sentence denotes HSPGs can be either membrane bound, or in secretory vesicles and in the extracellular matrix (86).
T160 6271-6377 Sentence denotes It has been shown that LF is able to prevent the internalization of some viruses by binding to HSPGs (86).
T161 6379-6403 Sentence denotes COVID-19 and Lactoferrin
T162 6404-6487 Sentence denotes COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
T163 6488-6654 Sentence denotes Many COVID-19 patients develop acute respiratory distress syndrome (ARDS), which leads to pulmonary edema and lung failure, and have liver, heart, and kidney damages.
T164 6655-7116 Sentence denotes These symptoms are associated with a cytokine storm (166, 167) manifesting elevated serum levels of interleukin (IL) IL-1β, IL-2, IL-7, IL-8, IL-9, IL-10, IL-17, granulocyte colony-stimulating factor (G-CSF), Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), interferon (IFN)γ, tumor necrosis factor (TNF)α, Interferon gamma-induced protein 10 (IP10), Monocyte Chemoattractant Protein-1 (MCP1), macrophage inflammatory protein 1(MIP1)A and MIP1B (168).
T165 7117-7215 Sentence denotes IL-22, in collaboration with IL-17 and TNFα, induces antimicrobial peptides in the mucosal organs.
T166 7216-7486 Sentence denotes IL-22 also upregulates mucins, fibrinogen, anti-apoptotic proteins, serum amyloid A, and LPS binding protein (169); therefore, IL-22 may contribute to the formation of life-threatening oedema with mucins and fibrin (170), seen in SARS-CoV-22 and SARS-CoV patients (168).
T167 7487-7617 Sentence denotes The 2003 SARS-CoV strain, that also causes severe acute respiratory syndrome, attaches to host cells via host receptor ACE2 (171).
T168 7618-7789 Sentence denotes This type I integral membrane protein receptor is a well-known receptor for respiratory viruses, and is abundantly expressed in tissues lining the respiratory tract (111).
T169 7790-7879 Sentence denotes During COVID-19 infection, SARS-CoV-2 also enters host cells via the ACE2 receptor (172).
T170 7880-8052 Sentence denotes ACE2 is highly expressed on human lung alveolar epithelial cells, enterocytes of the small intestine, and the brush border of the proximal tubular cells of the kidney (99).
T171 8053-8200 Sentence denotes HSPGs are also one of the preliminary docking sites on the host cell surface and play an important role in the process of SARS-CoV cell entry (99).
T172 8201-8345 Sentence denotes There is no current confirmed information that SARS-CoV-2 binds to HSPGs, however, LF blocks the infection of SARS-CoV by binding to HSPGs (99).
T173 8346-8429 Sentence denotes It is not presently known whether LF binds to ACE2, but it does bind to HSPGs (99).
T174 8430-8566 Sentence denotes Whether SARS-CoV-2 also enters host cells via HPSGs in the same way, as does (the 2003) SARS-CoV clearly warrants further investigation.
T175 8567-8690 Sentence denotes Of particular interest, and in the context of this paper, is the set of interactions between SARS-CoV-2 and host platelets.
T176 8691-8795 Sentence denotes This is of importance, as COVID-19 infection, can cause hyperinflammation due to a cytokine storm (166).
T177 8796-8909 Sentence denotes Pathogens like the influenza virus and Francisella tularensis, do trigger life-threatening cytokine storms (173).
T178 8910-9067 Sentence denotes Such a cytokine storm will significantly affect platelets, as platelets have many receptors where these inflammatory molecules may bind (173) (see Figure 5).
T179 9068-9229 Sentence denotes Circulating cytokines and inflammagens will hyperactivate platelets, causing low platelet count (thrombocytopenia), and a significant chance of hypercoagulation.
T180 9230-9433 Sentence denotes Thrombocytopenia is associated with increased risk of severe disease and mortality in patients with COVID-19, and thus serves as clinical indicator of worsening illness during hospitalization (174, 175).
T181 9434-9576 Sentence denotes Patients with type 2 diabetes are also particularly prone to increased levels of circulating inflammatory cytokines and hypercoagulation (76).
T182 9577-9761 Sentence denotes COVID-19 patients without other comorbidities but with diabetes are at higher risk of severe pneumonia, excessive uncontrolled inflammatory responses and a hypercoagulable state (176).
T183 9762-10114 Sentence denotes Guo and co-workers in 2020 also found that serum levels of IL-6, C-reactive protein, serum ferritin, and D-dimer, were significantly higher in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of the patient with COVID-19 (140).
T184 10115-10191 Sentence denotes Acute pulmonary embolism has also been reported in COVID-19 infection (177).
T185 10192-10331 Sentence denotes Focal accumulation of activated platelets within the oedematous area ex vivo correlated well with the size of the pulmonary embolism (178).
T186 10332-10539 Sentence denotes Interestingly, anticoagulant therapy, mainly with (intravenous) heparin (and mainly with low molecular weight heparin, LMWH), appears to be associated with better prognosis in severe COVID-19 patients (179).
T187 10540-10776 Sentence denotes Figure 5 Simplified platelet signaling and receptor activation during disease with main dysregulated molecules thrombin, fibrin(ogen), von Willebrand Factor (vWF) interleukins (IL) like IL-1α, IL-1β, and IL17A and cytokines like TNF-α.
T188 10777-10833 Sentence denotes Diagram created with BioRender (https://biorender.com/).
T189 10834-11085 Sentence denotes In COVID-19 infection, LF may have a role to play in not only sequestering iron and inflammatory molecules that are severely increased during the cytokine burst, but also possibly in assisting in occupying receptors and HSPGs to prevent virus binding.
T190 11086-11168 Sentence denotes Receptor occupancy is an important characteristic of LF, when taken as supplement.
T191 11169-11296 Sentence denotes Furthermore, it may assist in preventing thrombocytopenia, and hypercoagulation, both prominent features of COVID-19 infection.