1,721,002 research outputs found
Mutational analysis of the cysteine-rich region of the iron-responsive GATA factor Fep1. Role of individual cysteines as [2Fe–2S] cluster ligands
No full textFep1, the iron-dependent GATA-type transcriptional repressor of the methylotrophic yeast Pichia pastoris, has a dimeric structure and binds an iron–sulfur cluster of the [2Fe–2S] type. In this work, we extend the characterization of this protein by analysis of the optical and CD spectroscopic properties of a set of mutants where cysteines within the conserved Cys-X5-Cys-X8-Cys-X2-Cys motif have been targeted, in order to evaluate their role as [2Fe–2S] ligands. The results suggest that all four cysteine residues are essential because replacing them with serines in different combinations invariably produces a protein unable to correctly bind the [2Fe–2S] cluster
Fat Checking: Emerging Role of Lipids in Metabolism and Disease
Full text linkLipids are hydrophobic molecules involved in a plethora of biological functions; for example, they are employed for the storage of energy, serve as essential constituents of cell membranes and participate in the assembly of bilayer configuration [...
Neutralizing activity of usnic acid and β-cyclodextrins complex against SARS-CoV-2 spike pseudovirus
Full text link: The rapid spread of SARS-CoV-2 and its infection severity require an urgent development of antiviral agents. In this respect, Usnic acid (UA), a natural dibenzofuran derivative, exerts antiviral activity against several viruses, though presenting very low solubility and high cytotoxicity. Here, UA was complexed with β-cyclodextrins (β-CDs), a pharmaceutical excipient used to improve drug solubility. The cytotoxic activity, tested on Vero E6 cells, revealed no effect for β-CDs alone whereas significant cytotoxicity for the UA/β-CDs complex was recorded at concentrations ≥ 0.05%. The neutralizing activity towards the fusion of SARS-CoV-2 Spike Pseudovirus showed no effects for β-CDs alone whereas the UA/β-CDs complex, when pre-incubated with the viral particles, efficiently inhibited the Pseudoviral fusion of about 90 and 82% at non-cytotoxic concentrations of 0.03 and 0.01%, respectively. In conclusion, although further evidences are needed to clarify the exact inhibition mechanism, UA/β-CDs complex could be useful in SARS-CoV-2 infection
Lactoferrin, the moonlighting protein of innate immunity
Full text linkLactoferrin (Lf), a naturally occurring glycoprotein involved in innate immunity, was first discovered in bovine milk [...]
Efficacy of bovine lactoferrin in the post-surgical treatment of patients suffering from bisphosphonate-related osteonecrosis of the jaws: an open-label study
No full textOsteonecrosis of the jaws is an emerging pathological condition characterized by un-exposure or exposure of the necrotic bone, independently from the etiology. This term is usually referred to medication-related osteonecrosis of the jaws due to severe adverse reaction to certain medicines, as bisphosphonates, used for the treatment of cancer and osteoporosis. The management of patients with Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ) remains challenging because surgical and medical interventions may not eradicate this pathology. The goal of treatment of patients at risk of developing BRONJ or of those who have active disease is the preservation of quality of life by controlling pain, managing infection, and preventing the development of new areas of necrosis. The treatment of osteonecrosis consists in the surgical removal of necrotic bone followed by antibiotic therapy and application of sterile greasy gauze until the wound closure. The classical medical treatment has been compared with the innovative one consisting in the application of sterile greasy gauze soaked with bovine lactoferrin (bLf) after surgery. Here, for the first time, bLf efficacy on wound repair in subjects suffering from BRONJ with the progressive destruction of bone in the mandible or maxilla has been demonstrated. The positive results consist in a significant shorter time of wound closure (1 or 2 weeks) compared to that observed with classical surgical treatment (2-3 months). These promising results are an interesting tool for the innovative treatment of this pathology and for increasing the quality of life of these patients
An overview on in vitro and in vivo antiviral activity of lactoferrin: its efficacy against SARS-CoV-2 infection
Full text linkBeyond the absolute and indisputable relevance and efficacy of anti-SARS-CoV-2 vaccines, the rapid transmission, the severity of infection, the absence of the protection on immunocompromised patients, the propagation of variants, the onset of infection and/or disease in vaccinated subjects and the lack of availability of worldwide vaccination require additional antiviral treatments. Since 1987, lactoferrin (Lf) is well-known to possess an antiviral activity related to its physico-chemical properties and to its ability to bind to both heparan sulfate proteoglycans (HSPGs) of host cells and/or surface components of viral particles. In the present review, we summarize in vitro and in vivo studies concerning the efficacy of Lf against DNA, RNA, enveloped and non-enveloped viruses. Recent studies have revealed that the in vitro antiviral activity of Lf is also extendable to SARS-CoV-2. In vivo, Lf oral administration in early stage of SARS-CoV-2 infection counteracts COVID-19 pathogenesis. In particular, the effect of Lf on SARS-CoV-2 entry, inflammatory homeostasis, iron dysregulation, iron-proteins synthesis, reactive oxygen formation, oxidative stress, gut-lung axis regulation as well as on RNA negativization, and coagulation/fibrinolysis balance will be critically reviewed. Moreover, the molecular mechanisms underneath, including the Lf binding to HSPGs and spike glycoprotein, will be disclosed and discussed. Taken together, present data not only support the application of the oral administration of Lf alone in asymptomatic COVID-19 patients or as adjuvant of standard of care practice in symptomatic ones but also constitute the basis for enriching the limited literature on Lf effectiveness for COVID-19 treatment
Editorial. Nutraceuticals. New perspectives and approaches in human health and disease
Full text linkEfficacy of lactoferrin oral administration in the treatment of anemia and anemia of inflammation in pregnant and non-pregnant women: an interventional study
Full text linkThe discovery of the ferroportin-hepcidin complex has led to a critical review on the treatment of anemia and anemia of inflammation (AI). Ferroportin, the only known mammalian iron exporter from cells to blood, is negatively regulated by hepcidin, a hormone peptide able to bind to ferroportin, leading to its degradation. Therefore, new efficient therapeutic interventions acting on hepcidin and ferroportin are imperative to manage anemia and AI. Bovine milk derivative lactoferrin (bLf), a glycoprotein able to chelate two ferric ions per molecule, is emerging as a natural anti-inflammatory substance able to modulate hepcidin and ferroportin synthesis through the down-regulation of interleukin-6 (IL-6). Here, an interventional study (ClinicalTrials.gov Identifier: NCT01221844) was conducted by orally administering 100 mg of 20-30% iron-saturated bLf (corresponding to 70-84 μg of elemental iron) twice a day. This treatment was compared with the Italian standard therapy, consisting in the oral administration of 329.7 mg of ferrous sulfate once a day (corresponding to 105 mg of elemental iron). Treatments were carried out on 29 anemic women with minor ß-thalassemia (20 pregnant and 9 non-pregnant), 149 women with hereditary thrombophilia (HT) (70 pregnant and 79 non-pregnant) affected by AI and 20 anemic pregnant women suffering from various pathologies. In anemic pregnant and non-pregnant women with minor ß-thalassemia, presenting undetectable hepcidin levels, differently from ferrous sulfate management, bLf decreased IL-6 (from 25 ± 8 to 6 ± 3 pg/ml) and increased total serum iron (TSI) (from 54 ± 17 to 80 ± 9 μg/dl). BLf was also more efficient than ferrous sulfate in AI treatment in HT pregnant and non-pregnant women by decreasing both serum IL-6 (from 89 ± 8 to 58 ± 6 pg/ml) and hepcidin (from 115 ± 23 to 65 ± 10 ng/ml), thus increasing hematological parameters, such as the number of red blood cells (RBCs), the concentration of hemoglobin, TSI and serum ferritin. BLf was also efficient in treating anemia in other pathological pregnancies. Taken together all the results, bLf, showing a greater benefit and efficacy than the standard ferrous sulfate management, can be considered as a promising compound in treating anemia and AI through its ability to down-regulate IL-6, thus restoring ferroportin-mediated iron export from cells to blood in a hepcidin-dependent or independent way
Aerosolized bovine lactoferrin reduces neutrophils and pro-inflammatory cytokines in mouse models of Pseudomonas aeruginosa lung infections
Full text linkLactoferrin (Lf), an iron-chelating glycoprotein of innate immunity, produced by exocrine glands and neutrophils in
infection/inflammation sites, is one of the most abundant defence molecules in airway secretions. Lf, a pleiotropic molecule,
exhibits antibacterial and anti-inflammatory functions. These properties may play a relevant role in airway infections characterized
by exaggerated inflammatory response, as in Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) subjects. To
verify the Lf role in Pseudomonas aeruginosa lung infection, we evaluated the efficacy of aerosolized bovine Lf (bLf) in mouse
models of P. aeruginosa acute and chronic lung infections. C57BL/6NCrl mice were challenged with 106 CFUs of P. aeruginosa PAO1
(acute infection) or MDR-RP73 strain (chronic infection) by intra-tracheal administration. In both acute and chronic infections,
aerosolized bLf resulted in nonsignificant reduction of bacterial load but significant decrease of the neutrophil recruitment and
pro-inflammatory cytokine levels. Moreover, in chronic infection the bLf-treated mice recovered body weight faster and to a
higher extent than the control mice. These findings add new insights into the benefits of bLf as a mediator of general health and
its potential therapeutic applications
Lactoferrin in Aseptic and Septic Inflammation
Full text linkLactoferrin (Lf), a cationic glycoprotein able to chelate two ferric irons per molecule, is synthesized by exocrine glands and neutrophils. Since the first anti-microbial function attributed to Lf, several activities have been discovered, including the relevant anti-inflammatory one, especially associated to the down-regulation of pro-inflammatory cytokines, as IL-6. As high levels of IL-6 are involved in iron homeostasis disorders, Lf is emerging as a potent regulator of iron and inflammatory homeostasis. Here, the role of Lf against aseptic and septic inflammation has been reviewed. In particular, in the context of aseptic inflammation, as anemia of inflammation, preterm delivery, Alzheimer’s disease and type 2 diabetes, Lf administration reduces local and/or systemic inflammation. Moreover, Lf oral administration, by decreasing serum IL-6, reverts iron homeostasis disorders. Regarding septic inflammation occurring in Chlamydia trachomatis infection, cystic fibrosis and inflammatory bowel disease, Lf, besides the anti-inflammatory activity, exerts a significant activity against bacterial adhesion, invasion and colonization. Lastly, a critical analysis of literature in vitro data reporting contradictory results on the Lf role in inflammatory processes, ranging from pro- to anti-inflammatory activity, highlighted that they depend on cell models, cell metabolic status, stimulatory or infecting agents as well as on Lf iron saturation degree, integrity and purity
- …
