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Lactoferrin (Lf), a multifunctional cationic glycoprotein extracted from milk or colostrum, is able to chelate two ferric ions per molecule, inhibit the formation of reactive oxygen species, interact with the anionic components of bacteria or host cells, and enter inside host cell nucleus, thereby exerting antibacterial, anti-invasive, and anti-inflammatory activities. By virtue of Lf presence, bovine colostrum is expected to perform analogous functions to pure Lf, along with additional activities attributable to other bioactive constituents. The present research aims to compare the antibacterial, anti-invasive, and anti-inflammatory activities of bovine Lf purified from milk (mbLf) and colostrum (cbLf) in comparison to those exhibited by whole bovine colostrum (wbc). The results demonstrated a major efficacy of mbLf in inhibiting pathogenic bacteria and in exerting anti-invasive and anti-survival activities with respect to cbLf and wbc. Furthermore, mbLf lowered IL-6 levels to those of uninfected cells, while a less evident decrease was observed upon cbLf treatment. Conversely, wbc managed to slightly lower IL-6 levels compared to those synthesized by infected cells. These data demonstrate that, to obtain maximum effectiveness in such activities, Lf should be formulated/used without addition of other substances and should be sourced from bovine milk rather than colostrum. [ABSTRACT FROM AUTHOR]

Bovine lactoferrin (bLF) is a naturally occurring glycoprotein with antibacterial and antiviral activities. We evaluated whether bLF can prevent viral infections in the human intestinal epithelial cell line Caco-2. To assess antiviral responses, we measured the levels of interferon (IFN) expression, IFN-stimulated gene expression, and infection with a pseudotyped virus bearing either severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein or vesicular stomatitis virus (VSV)-G protein after treatment of cells with both bLF and polyinosinic-polycytidylic acid, an analog of double-stranded RNA that mimics viral infection. Combination treatment of cells with both bLF and polyinosinic-polycytidylic acid increased mRNA and protein expression of several IFN genes (IFNB, IFNL1, and IFNL2) and IFN-stimulated genes (ISG15, MX1, IFITM1, and IFITM3) in Caco-2 cells. However, treatment with bLF alone did not induce an antiviral response. Furthermore, combination treatment suppressed infection of the SARS-CoV-2 pseudotyped virus more efficiently than did bLF treatment alone, even though combination treatment increased the expression of mRNA encoding ACE2. These results indicate that bLF increases the antiviral response associated with the double-stranded RNA-stimulated signaling pathway. Our results also suggest that bLF and double-stranded RNA analogs can be used to treat viral infections, including those caused by SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The article presents New insights into the systemic effects of oral lactoferrin: transcriptome profiling. Topics discussed include the immunomodulatory nature of lactoferrin (LF) derives from its ability to bridge innate and adaptive immunity in obtaining physiological equilibrium; and the aim of this study was to evaluate the systemic effects of orally and intravenously (IV) administered recombinant human LF (rhLF) on blood cell transcriptome profiling.

The article presents Effect of bovine lactoferrin on prevention of late-onset sepsis in infants, and pooled analysis of individual patient data from two randomized controlled trials. Topics discussed include the aim of this study was to determine the preventative effects of bLF on culture-proven or probable LOS in infants; and determine the effect of bLF in relation to intake of human milk, both trial designs had similar inclusion and exclusion criteria, the same dose of bLF.

The article presents synthetic mimic of the two antimicrobial domains of bovine lactoferrin. Topics discussed include this review describes how saliva has been the guideline for the design and characterization of a heterodimeric antimicrobial construct called LFchimera; and this construct mimics the helical parts of two antimicrobial domains in the crystal structure of bovine lactoferrin. I.

The article presents Antibiofilm activity of lactoferrin-derived synthetic peptides against Pseudomonas aeruginosa PAO1. Topics discussed include pathogenic bacteria can protect themselves from the effects of antibiotics and the host immune response system by forming biofilms; and Biofilms are polymer-entrapped bacterial cells, which adhere to each other and are often attached to a surface.

The article presents Dose escalation study of bovine lactoferrin in preterm infants. Topics discussed include Lactoferrin as a nutritional enteral supplement has emerged as a novel preventative therapy against serious infections in preterm infants, although neonatal studies have demonstrated variable results; and studies examining higher doses of lactoferrin, length of treatment, and potency of different products will aid in determining the optimal approach for the use of lactoferrin.

The article presents Biological activities of commercial bovine lactoferrin sources. Topics discussed include the purity and protein form of each Lf were examined by SDS–PAGE, Western blot, and proteomics analysis; and assays were conducted to evaluate uptake of Lfs and iron from Lfs by enterocytes as well as Lf bioactivities, including effects on intestinal cell proliferation and differentiation, IL-18 secretion, TGF-b1 transcription, and growth of enteropathogenic Escherichia coli (EPEC).

The article presents Binding of lactoferrin to the surface of low-density lipoproteins modified by myeloperoxidase prevents intracellular cholesterol accumulation by human blood monocytes. Topics discussed include Myeloperoxidase (MPO) is a unique heme-containing peroxidase that can catalyze the formation of hypochlorous acid (HOCl); and the strong interaction of MPO with low-density lipoproteins (LDL) promotes proatherogenic modification of LDL by HOCl.

The article presents evidence from systematic reviews of randomized trials on enteral lactoferrin supplementation in preterm neonates. Topics discussed include summarize the current evidence from randomized controlled trials on enteral lactoferrin supplementation in preterm neonates; and meta-analysis suggests clinical benefit in decreasing late-onset sepsis, late-onset fungal sepsis, length of stay in the hospital and urinary tract infections.

The article presents Comparative effect of bovine buttermilk, whey, and lactoferrin on the innate immunity receptors and oxidative status of intestinal epithelial cells. Topics discussed include Milk contains bioactive molecules with important functions as defensive proteins; among them are the whey protein lactoferrin and proteins of the milk fat globule membrane (MFGM) present in buttermilk; and the aim of this study has been to investigate the effects of lactoferrin, whey, and buttermilk.

The article presents Lactoferrin and hematoma detoxification after intracerebral hemorrhage. Topics discussed include discuss the role of lactoferrin (LTF) in detoxifying hematoma after intracerebral hemorrhage (ICH). Subsequent to ICH, neutrophils enter the ICH-affected brain; and LTF is an iron-binding glycoprotein that binds Fe3+ with high affinity.

The article presents N-glycans of lactoferrin. Topics discussed include this minireview summarizes several studies dealing with the diverse glycosylation patterns of lactoferrin from different origins, and the potential impact of these post-translational modifications on the functionality of lactoferrin; and special emphasis is placed on the differences between human and bovine lactoferrin, because the latter form is often selected for the development of novel therapeutic approaches in humans.

The article presents Lactoferrin levels in cervical fluid from in vitro fertilization (IVF) patients correlation with IVF parameters. Topics discussed include lactoferrin (LF) might have roles in the reproductive process and that its levels might change in the female tract as a response to various factors; and the aim of this investigation was to assess whether LF levels in cervical secretions correlate with reproductive parameters from in vitro fertilization (IVF) patients.

The article presents the effects of oral bovine lactoferrin on a mouse model of inflammation associated colon cancer. Topics discussed include Patients with ulcerative colitis or colonic Crohn's disease have a significantly increased risk of developing colorectal cancer; and Bovine lactoferrin (bLF) reportedly inhibited the development of colon cancer in rats and mice, and in a placebo controlled trial, ingestion of bLF inhibited the growth of intestinal polyps.

The article presents Lactoferrin, a versatile natural antimicrobial glycoprotein that modulates the host's innate immunity. Topics discussed include the antimicrobial activity of lactoferrin was the first to be discovered and was assumed to be solely dependent on its iron-chelating ability; and review the current understandings of the antimicrobial effect, interaction with host cells, and innate immune modulation of lactoferrin.

The article presents Lactoferrin receptors in Gram-negative bacteria: an evolutionary perspective. Topics discussed include these events led to the appearance of the lactoferrin gene, which has since been exploited into adopting countless new functions, including the provision of highly bactericidal degradation products; and parallel to lactoferrin's evolution, evolving bacterial receptors have countered the bactericidal properties of this innate immunity protein.

The article presents prospective on multiple biological activities of lactoferrin contributing to piglet welfare. Topics discussed include this review examines the following known beneficial effects of lactoferrin: improves the digestion and capacity for absorption in the intestinal tract; and promotes the absorption of iron and reduces the incidence of iron deficiency anemia.

The article presents Bovine lactoferrin and lactoferrin peptides affect endometrial and cervical cancer cell lines. Topics discussed include the bLF and LF peptides inhibited the proliferation of uterine cancer cells and caused cellular morphological changes and damage to cell monolayers; and bLF induced apoptosis, LFcin17–30 and LFampin265–284 induced apoptosis and necrosis, and LF chimera induced necrosis.

The article presents ELFIN, the United Kingdom preterm lactoferrin trial: interpretation and future questions. Topics discussed include results from previous studies have suggested that supplemental bovine lactoferrin (BLF) given to preterm infants reduces late-onset sepsis (LOS) and necrotising enterocolitis (NEC); and the Enteral Lactoferrin in Neonates (ELFIN) study, performed in the Grate Britain, aimed to further address this issue with a well powered double-blind placebo controlled trial.

The article presents Lactoferrin reduces mycobacterial M1-type inflammation induced with trehalose 6,6'-dimycolate and facilitates the entry of fluoroquinolone into granulomas. Topics discussed include Primary infection with Mycobacterium tuberculosis (Mtb) results in the formation of a densely packed granulomatous response that essentially limits the entry and efficacy of immune effector cells; and the physical nature of the granuloma does not readily permit the entry of therapeutic agents.

The article presents Lactoferrin and oral pathologies. Topics discussed include the oral cavity is a non-uniform, extraordinary environment characterized by mucosal, epithelial, abiotic surfaces and secretions as saliva; and commensals exert an important role in host defenses, while pathogenic microorganisms can nullify this protective function causing oral and systemic diseases.

The article presents Antiviral effects of bovine lactoferrin on human norovirus. Topics discussed include Human noroviruses cause significant morbidity and mortality worldwide, but lack approved antivirals or vaccines to treat or prevent infections; and the recent development of two cell culture systems in human transformed B cells (BJABs) and non-transformed human intestinal enteroid cultures overcomes a main limitation in identifying molecules with anti-norovirus activities.

The article presents ELFIN, the United Kingdom preterm lactoferrin trial: interpretation and future questions. Topics discussed include results from previous studies have suggested that supplemental bovine lactoferrin (BLF) given to preterm infants reduces late-onset sepsis (LOS) and necrotising enterocolitis (NEC); and the Enteral Lactoferrin in Neonates (ELFIN) study, performed in the Grate Britain, aimed to further address this issue with a well powered double-blind placebo controlled trial.

Lactoferrin supplementation may help prevent infections in preterm infants, but the efficacy has varied with different doses and products. We assessed the absorption and excretion of bovine lactoferrin (bLF) in 31 infants receiving 100, 200, or 300 mg·kg–1·day–1 of enteral bLF for 30 days. bLF and human lactoferrin (hLF) in infant saliva, blood, urine, and stool, as well as expressed (EBM) or donor breast milk (DBM) that were collected (i) before the treatment was initiated, (ii) at study day 22, and (iii) one week after treatment cessation, were measured using ELISA. During treatment, bLF was absorbed from the gastrointestinal tract and detected in plasma, saliva, and urine, as well as excreted in stool. Levels of bLF in the saliva and stool began to decline within 12 h after dosing, and bLF was undetectable in all samples one week after treatment. The concentrations of hLF exceeded those of bLF across sample types and time-points. Infants receiving EBM demonstrated higher levels of hLF in the saliva and stool than those receiving DBM. Neither bLF nor hLF levels varied by patient characteristics, bLF dosage, or infection status. This is the first study demonstrating bLF absorption into the bloodstream and distribution to saliva and urine in preterm infants. Future studies should further explore LF pharmacokinetics because higher and more frequent dosing may improve the clinical benefit of LF supplementation. [ABSTRACT FROM AUTHOR]

Results from previous studies have suggested that supplemental bovine lactoferrin (BLF) given to preterm infants (<32 weeks gestation) reduces late-onset sepsis (LOS) and necrotising enterocolitis (NEC). The Enteral Lactoferrin in Neonates (ELFIN) study, performed in the UK, aimed to further address this issue with a well powered double-blind placebo controlled trial of >2200 preterm infants. The results from ELFIN did not demonstrate a reduction in LOS or NEC, or several other clinically important measures. Of the 1093 infants, 316 (29%) in the intervention group developed late-onset sepsis versus 334 (31%) of 1089 in the control group, with an adjusted risk ratio of 0.95 (95% CI = 0.86–1.04; p = 0.233). Reasons for the differences in ELFIN trial results and other studies may include population differences, the routine use of antifungal prophylaxis in the UK, timing of administration of the lactoferrin in relation to disease onset, or specific properties of the lactoferrin used in the different trials. The UK National Institutes for Health Research funded "Mechanisms Affecting the Guts of Preterm Infants in Enteral feeding trials" (MAGPIE) study is further exploring the use of lactoferrin, and the results should be available soon. [ABSTRACT FROM AUTHOR]

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The short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is an important innate material in the upper airway, and lactoferrin (LF) aids the innate functions in humans. In this study, a nasal epithelial model was used to investigate how LF modulates SPLUNC1 to reduce the inflammatory process mediated by lipopolysaccharide (LPS). The inflammation of human RPMI-2650 cells was induced with LPS to evaluate SPLUNC1 expression after treating the cells with bovine LF (bLF). The interaction pathway between LF and SPLUNC1 in LPS-induced inflammation was further investigated. Our study reveals that the addition of bLF results in the recovery of SPLUNC1 expression in nasal epithelial cells under LPS-induced inflammation. MAPK is involved in the main pathway for the SPLUNC1 and bLF interaction. Decreased SPLUNC1 function could be recovered by addition of bLF. The MEK1/2-MAPK signaling pathway is crucial for the SPLUNC1 and bLF interaction. Therefore, LF could support SPLUNC1 in the innate immunity recovery process. [ABSTRACT FROM AUTHOR]

Lactoferrin (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. [ABSTRACT FROM AUTHOR]

Giardia intestinalis is the most common infectious protozoan parasite in children. Despite the effectiveness of some drugs, the disease remains a major worldwide problem. Consequently, the search for new treatments is important for disease eradication. Biological molecules with antimicrobial properties represent a promising alternative to combat pathogens. Bovine lactoferrin (bLF) is a key component of the innate host defense system, and its peptides have exhibited strong antimicrobial activity. Based on these properties, we evaluated the parasiticidal activity of these peptides on G. intestinalis. Trophozoites were incubated with different peptide concentrations for different periods of time, and the growth or viability was determined by carboxyfluorescein-succinimidyl-diacetate-ester (CFDA) and propidium iodide (PI) staining. Endocytosis of peptides was investigated by confocal microscopy, damage was analyzed by transmission and scanning electron microscopy, and the type of programmed cell death was analyzed by flow cytometry. Our results showed that the LF peptides had giardicidal activity. The LF peptides interacted with G. intestinalis and exposure to LF peptides correlated with an increase in the granularity and vacuolization of the cytoplasm. Additionally, the formation of pores, extensive membrane disruption, and programmed cell death was observed in trophozoites treated with LF peptides. Our results demonstrate that LF peptides exhibit potent in vitro antigiardial activity. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) is a multifunctional cationic protein (p I 8.2-8.9) in mammalian milk. We previously reported that enteric-LF prevented hypercholesterolemia and atherosclerosis in a diet-induced atherosclerosis model using Microminipig, although the underlying mechanisms remain unclear. Because LF is assumed to electrostatically interact with bile acids to inhibit intestinal cholesterol absorption, LF could promote cholesterol excretion. In this study, we assessed the interaction between LF and taurocholate in vitro, and the effect of LF on cholesterol excretion in rats. The binding rate of taurocholate to LF was significantly higher than that to transferrin (p I 5.2-6.3). When rats were administered a high-cholesterol diet (HCD) containing 5% LF, LF was detected using ELISA in the upper small intestine from 7.5 to 60 min after the administration. Rats were fed one of the following diets: control, HCD, or HCD + 5% LF for 21 days. Fecal neutral steroids and hepatic cholesterol levels in the HCD group were significantly higher than those in the control group. The addition of LF to a HCD significantly increased fecal neutral steroids levels (22% increase, p < 0.05) and reduced hepatic cholesterol levels (17% decrease, p < 0.05). These parameters were inversely correlated ( R = −0.63, p < 0.05). These results suggest that LF promotes cholesterol excretion via interactions with bile acids. [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf) is an iron-binding glycoprotein that is present at high concentrations in milk. Bovine lactoferricin (LfcinB) is a peptide fragment generated by pepsin proteolysis of bovine lactoferrin (bLf). LfcinB consists of amino acid residues 17-41 proximal to the N-terminus of bLf and a disulfide bond between residues 19 and 36, forming a loop. Both bLf and LfcinB have been demonstrated to have antitumor activities. Colorectal cancer is the second most common cause of cancer death in developed countries. We hypothesized that bLf and LfcinB exert antitumor activities on colon cancer cells (HT-29) by triggering various signaling pathways. bLf and LfcinB significantly induced apoptosis in HT-29 cells but not in normal human intestinal epithelial cells, as revealed by the ApoTox-Glo Triplex Assay. The LIVE/DEAD cell viability assay showed that both bLf and LfcinB reduced the viability of HT-29 cells. Transcriptome analysis indicated that bLf, cyclic LfcinB, and linear LfcinB exerted antitumor activities by differentially activating diverse signaling pathways, including p53, apoptosis, and angiopoietin signaling. Immunoblotting results confirmed that both bLf and LfcinBs increased expression of caspase-8, p53, and p21, critical proteins in tumor suppression. These results provide valuable information regarding bLf and LfcinB for potential clinical applications in colon cancer therapy. [ABSTRACT FROM AUTHOR]

We examined the in-vitro effects of bovine lactoferrin (LF) on the production of interferon-λ (IFN-λ), an antiviral cytokine important for the defense of enterocytes, using the human intestinal epithelial cell line HT-29. HT-29 cell cultures were treated with LF for 1 h, and the cultures were stimulated with polyinosinic-polycytidylic acid (poly I:C). LF increased the concentration of IFN-λ in the culture supernatant after stimulation in a dose-dependent manner. A similar increase in the concentration of IFN-λ was observed in the supernatant of cells washed between treatment with LF and stimulation with poly I:C. At 6 and 24 h after stimulation with poly I:C (early and late phases, respectively) treated cultures contained significantly higher concentrations of IFN-λ1 in the culture supernatant, and significantly higher IFN-λ1 and IFN-λ2 mRNA levels, than controls. These results suggest that LF activates the innate cellular immunity of the enterocytes to double-stranded RNA and increases the production of IFN-λ. [ABSTRACT FROM AUTHOR]

Lactoferrin exerts its biological activities by interacting with receptors on target cells, including LDL receptor-related protein-1 (LRP-1/CD91), intelectin-1 (omentin-1), and Toll-like receptor 4 (TLR4). However, the effects mediated by these receptors are not sufficient to fully explain the many functions of lactoferrin. C-X-C-motif cytokine receptor 4 (CXCR4) is a ubiquitously expressed G-protein coupled receptor for stromal cell-derived factor-1 (SDF-1/CXCL12). Lactoferrin was found to be as capable as SDF-1 in blocking infection by an HIV variant that uses CXCR4 as a co-receptor (X4-tropic HIV), suggesting that lactoferrin interacts with CXCR4. We addressed whether CXCR4 acts as a lactoferrin receptor using HaCaT human keratinocytes and Caco-2 human intestinal cells. We found that bovine lactoferrin interacted with CXCR4-containing lipoparticles, and that this interaction was not antagonized by SDF-1. In addition, activation of Akt in response to lactoferrin was abrogated by AMD3100, a small molecule inhibitor of CXCR4, or by a CXCR4-neutralizing antibody, suggesting that CXCR4 functions as a lactoferrin receptor able to mediate activation of the PI3K-Akt signaling pathway. Lactoferrin stimulation mimicked many aspects of SDF-1-induced CXCR4 activity, including receptor dimerization, tyrosine phosphorylation, and ubiquitination. Cycloheximide chase assays indicated that turnover of CXCR4 was accelerated in response to lactoferrin. These results indicate that CXCR4 is a potent lactoferrin receptor that mediates lactoferrin-induced activation of Akt signaling. [ABSTRACT FROM AUTHOR]

Lactoferrin is a multifunctional, iron-binding glycoprotein found in milk and other exocrine secretions. Lactoferrin in milk plays vital roles in the healthy development of newborn mammals, and is also an innate resistance factor involved in the prevention of mammary gland infection by microorganisms. Inflammation of the udder because of bacterial infection is referred to as mastitis. There have been many investigations into the relationships between lactoferrin and mastitis, which fall into several categories. The main categories are fluctuations in the lactoferrin concentration of milk, lactoferrin activity against mastitis pathogens, elucidation of the processes underlying the onset of mastitis, participation of lactoferrin in the immune system, and utilization of lactoferrin in mastitis treatment and prevention. This minireview describes lactoferrin research concerning bovine mastitis. In the 1970s, many researchers reported that the lactoferrin concentration fluctuates in milk from cows with mastitis. From the late 1980s, many studies clarified the infection-defense mechanism in the udder and the contribution of lactoferrin to the immune system. After the year 2000, the processes underlying the onset of mastitis were elucidated in vivo and in vitro, and lactoferrin was applied for the treatment and prevention of mastitis. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis is an obligate, intracellular pathogen responsible for the most common sexually transmitted bacterial disease worldwide, causing acute and chronic infections. The acute infection is susceptible to antibiotics, whereas the chronic one needs prolonged therapies, thus increasing the risk of developing antibiotic resistance. Novel alternative therapies are needed. The intracellular development of C. trachomatis requires essential nutrients, including iron. Iron-chelating drugs inhibit C. trachomatis developmental cycle. Lactoferrin (Lf), a pleiotropic iron binding glycoprotein, could be a promising candidate against C. trachomatis infection. Similarly to the efficacy against other intracellular pathogens, bovine Lf (bLf) could both interfere with C. trachomatis entry into epithelial cells and exert an anti-inflammatory activity. In vitro and in vivo effects of bLf against C. trachomatis infectious and inflammatory process has been investigated. BLf inhibits C. trachomatis entry into host cells when incubated with cell monolayers before or at the moment of the infection and down-regulates IL-6/IL-8 synthesized by infected cells. Six out of 7 pregnant women asymptomatically infected by C. trachomatis, after 30 days of bLf intravaginal administration, were negative for C. trachomatis and showed a decrease of cervical IL-6 levels. This is the first time that the bLf protective effect against C. trachomatis infection has been demonstrated. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) is an iron-binding basic glycoprotein that has an antimicrobial effect against certain microbes. The purpose of this study is to evaluate the amoebicidal effect of bovine milk LF (bLF) against Acanthamoeba clinical-isolate trophozoites, which cause severe keratitis. Most of the risk factor for Acanthamoeba keratitis is from wearing soft contact lenses (SCLs). Acanthamoeba trophozoites were incubated in bovine LF (bLF) solution, and the ratios of viability and encystment were determined with microscopic analysis of cyst formation. The amoebicidal effect of bLF was assessed by Trypan blue assay. The ratios of viable cells in the presence of iron-free bLF (apo-bLF), native-bLF, and iron-saturated bLF (Fe-bLF) at the concentration of 10 μmol/L for 60 min were 7.7% ± 4.6%, 80.7% ± 10.1%, and 97.3% ± 1.5%, respectively. Apo-bLF showed potent amoebicidal effect against Acanthamoeba trophozoites, but Fe-bLF did not have this effect. After treating with apo-bLF, most dead cells were nonglobular forms of trophozoites but not cystic forms. Encystment of Acanthamoeba was assessed by the sarkosyl-calcofluor white assay. The encystment ratios treated with 0.5% propylene glycol (positive control) and 10 μmol/L apo-bLF for 24 h were 96.12% ± 10.6% and 0.47% ± 0.5%, respectively. These results suggest that the amoebicidal effect of apo-bLF without encystment might lead to the prevention of contamination of Acanthamoeba in SCL stock cases. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of bovine lactoferrin (bLf) on melanin-producing cells and to elucidate its mechanism of action. We tested the anti-melanogenic effect of bLf on a 3-dimensional cultured pigmentation skin model and confirmed a 20% reduction in pigmentation, suggesting that bLf was transdermally absorbed and it suppressed melanin production. Treatment of human melanoma cells with bLf resulted in a significant, dose-dependent suppression of melanin production. Apo-bLf and holo-bLf suppressed melanogenesis to the same degree as bLf. The key feature behind this anti-melanogenic effect of bLf was the down-regulation of the microphthalmia-associated transcription factor (MITF), leading to the suppression of tyrosinase activity. Treatment with bLf resulted in both decreased expression of MITF mRNA and enhanced degradation of MITF protein. However, the primary effector was enhanced phosphorylation of extracellular signal-regulated kinase (ERK), leading to the phosphorylation and degradation of MITF. Our finding that bLf suppresses melanin production in melanocytes indicates that bLf is a possible candidate for application as a skin-whitening agent. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) is a protein with antimicrobial activity, which is conferred in part by 2 regions contained in its N-terminal lobe. These regions have been used to develop the following synthetic peptides: lactoferricin17-30, lactoferrampin265-284, and LF chimera (a fusion of lactoferricin17-30 and lactoferrampin265-284). We have reported that these LF peptides have antibacterial activity against several pathogenic bacteria; however, the exact mechanism of action has not been established. Here, we report the effects of LF peptides on the viability of enteroaggregative Escherichia coli (EAEC) and the ability of these peptides to penetrate into the bacteria cytoplasm. The viability of EAEC treated with LF peptides was determined via enumeration of colony-forming units, and the binding and internalization of the LF peptides was followed via immunogold labeling and electron microscopy. Treatment of EAEC with 20 and 40 μmol/L LF peptides reduced bacterial growth compared with untreated bacteria. Initially the peptides associated with the plasma membrane, but after 5 to 30 min of incubation, the peptides were found in the cytoplasm. Remarkably, bacteria treated with LF chimera developed cytosolic electron-dense structures that contained the antimicrobial peptide. Our results suggest that the antibacterial mechanism of LF peptides on EAEC involves their interaction with and penetration into the bacteria. [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf) is an iron-binding multifunctional protein, mainly present in external secretions. Lf is known to penetrate skin and may thus exert its multiple functions in skin. Sophorolipids (SLs) are glycolipid biosurfactants, which have been shown to enhance absorption of commercial bovine Lf (CbLf) in model skin via forming an assembly with CbLf. In this study, uptake and post-internalization localization of bovine Lf (bLf), CbLf, and human Lf (hLf) with or without forming assemblies with SLs in human dermal fibroblasts (HDFn) were determined using 125I-labeled Lfs and confocal microscopy, respectively. Our results show that all 3 Lfs were internalized by HDFn; although SLs did not significantly affect the uptake of Lfs, it changed Lf localization by accumulating Lfs in the perinuclear region. Furthermore, microarrays were used to investigate transcriptional profiling in HDFn in response to CbLf, SLs, or CbLf-SLs-assembly treatments. Transcriptome profiling indicates that CbLf may play roles in the protection of skin from oxidative stress, immunomodulatory activities, and enhancement of wound healing. The assembly had similar effects but dramatically modulated the transcription of some genes. SLs alone modified signaling pathways related to lipid metabolism, as well as synthesis of sex hormones and vitamins. Thus, CbLf may exert beneficial effects on skin, and these effects may be modulated by SLs. [ABSTRACT FROM AUTHOR]

Pathogenic bacteria from the families Neisseriaeceae and Moraxellaceae acquire iron from their host using surface receptors that have the ability to hijack iron from the iron-sequestering host proteins transferrin (Tf) and lactoferrin (Lf). The process of acquiring iron from Tf has been well-characterized, including the role of the surface lipoprotein transferrin-binding protein B (TbpB). In contrast, the only well-defined role for the homologue, LbpB, is in its protection against cationic antimicrobial peptides, which is mediated by regions present in some LbpBs that are highly enriched in glutamic or aspartic acid. In this study we compare the Tf-TbpB and the Lf-LbpB interactions and examine the protective effect of LbpB against extracts from human and transgenic mouse neutrophils to gains insights into the physiological roles of LbpB. The results indicate that in contrast to the Tf-TbpB interaction, Lf-LbpB interaction is sensitive to pH and varies between species. In addition, the results with transgenic mouse neutrophils raise the question of whether there is species specificity in the cleavage of Lf to generate cationic antimicrobial peptides or differences in the potency of peptides derived from mouse and human Lf. [ABSTRACT FROM AUTHOR]

To understand the protein-surfactant interactions between naturally derived sophorolipids (SLs) and bovine lactoferrin (bLf), we carried out spectroscopic, microscopic, and biochemical experiments under weakly acidic and neutral pH conditions. Particle size analysis, microscopy, and enzymatic digestion indicated that bLf and SLs interact with each other to form sheet-like and small aggregated structures reflecting the original self-organization of SLs at pH 5.0 and 7.0, respectively. Circular dichroism (CD) showed that SLs did not significantly affect the secondary structure of bLf. [ABSTRACT FROM AUTHOR]

Trehalose 6′6-dimycolate (TDM) is the most abundant glycolipid on the cell wall of Mycobacterium tuberculosis (MTB). TDM is capable of inducing granulomatous pathology in mouse models that resembles those induced by MTB infection. Using the acute TDM model, this work investigates the effect of recombinant human and mouse lactoferrin to reduce granulomatous pathology. C57BL/6 mice were injected intravenously with TDM at a dose of 25 μg·mouse−1. At day 4 and 6, recombinant human or mouse lactoferrin (1 mg·(100 μL)−1·mouse−1) were delivered by gavage. At day 7 after TDM injection, mice were evaluated for lung pathology, cytokine production, and leukocyte populations. Mice given human or mouse lactoferrin had reduced production of IL-12p40 in their lungs. Mouse lactoferrin increased IL-6 and KC (CXCL1) in lung tissue. Increased numbers of macrophages were observed in TDM-injected mice given human or mouse lactoferrin. Granulomatous pathology, composed of mainly migrated leukocytes, was visually reduced in mice that received human or mouse lactoferrin. Quantitation of granulomatous pathology demonstrated a significant decrease in mice given human or mouse lactoferrin compared with TDM control mice. This report is the first to directly compare the immune modulatory effects of both heterologous recombinant human and homologous mouse lactoferrin on the development of TDM-induced granulomas. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) is a breast milk glycoprotein with antimicrobial and anti-inflammatory effects. Its beneficial properties in infants, especially in those born preterm, are currently being studied in clinical trials. However, the maternal and nursing infant factors that may affect LF concentration in breast milk are still not clear. We conducted a systematic review to investigate the factors that may affect the concentration of LF in breast milk. We used a 2-step approach to identify the eligible studies according to inclusion/exclusion criteria, and to determine which studies would be considered. We included 70 qualified articles from 29 countries with publication dates ranging from 1976 to 2015. We described the correlation between LF concentration in breast milk and lactation stage; 10 maternal factors, such as race, parity, among others; and 2 infant factors: infections and prematurity. Colostrum has the highest LF levels, but they decrease with days postpartum. No other factor has been consistently associated with LF concentration. A major limitation of the majority of the published studies is the small sample size and the different methods used to measure LF concentration. Therefore, there is a need for large, multicenter studies with standardized study design, sample collection, and LF measurement methods to identify clinically significant factors associated with LF expression in breast milk, which will help promote exclusive breastfeeding in preterm infants. [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf), a multifunctional glycoprotein, is an important antimicrobial and immune regulatory protein present in neutrophils and most exocrine secretions of mammals. Lactoferricin (Lfcin) is located in the N-terminal region of this protein. In this review, the current state of research into Lf and Lfcin in China is described. Searching with HistCite software in Web Sci located 118 papers published by Chinese researchers from 2011-2015, making China one of the top 3 producers of Lf research and development in the world. The biological functions of Lf and Lfcin are discussed, including antibacterial, antiviral, antifungal, anticarcinogenic, and anti-inflammatory activities; targeted drug delivery, induction of neurocyte, osteoblast, and tenocyte growth, and possible mechanisms of action. The preparation and heterologous expression of Lf in animals, bacteria, and yeast are discussed in detail. Five Lf-related food additive factories and 9 Lf-related health food production companies are certified by the China Food and Drug Administration (CFDA). The latest progress in the generation of transgenic livestock in China, the safety of the use of transgenic animals, and future prospects for the uses of Lf and Lfcin are also covered. [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf) is the major whey protein in milk, with multiple beneficial health effects including direct antimicrobial activities, anti-inflammatory effects, and iron homeostasis. Oral Lf supplementation in human preterm infants has been shown to reduce the incidence of sepsis and necrotizing enterocolitis. In preclinical models of antenatal stress and perinatal brain injury, bovine Lf protected the developing brain from neuronal loss, improved connectivity, increased neurotrophic factors, and decreased inflammation. It also supported brain development and cognition. Further, Lf can prevent preterm delivery by reducing proinflammatory factors and inhibiting premature cervix maturation. We review here the latest research on Lf in the field of neonatology. [ABSTRACT FROM AUTHOR]

The purpose of this study was to elucidate the effects of bovine lactoferrin on keratinocyte differentiation and barrier function. Addition of bovine lactoferrin to differentiating HaCaT human keratinocytes led to increased transepithelial electrical resistance (TER), a marker of epithelial barrier function. This elevation was followed by upregulation of two differentiation markers, involucrin and filaggrin. The expression level of sterol regulatory element-binding protein-1 was also enhanced by bovine lactoferrin. The lactoferrin-induced upregulation of involucrin and filaggrin expression were confirmed in normal human epidermal keratinocytes (NHEK). Treatment with SB203580, a p38 mitogen-activated protein kinase (MAPK) α inhibitor, impaired the upregulation of involucrin and filaggrin expression in response to lactoferrin. The elevation of p38 MAPK phosphorylation was further enhanced by lactoferrin in the initial stage of differentiation of HaCaT keratinocytes. The findings suggest that bovine lactoferrin promotes epithelial differentiation by a p38-MAPK-dependent mechanism. [ABSTRACT FROM AUTHOR]

A 22-year-old male suffering from abdominal pain, repeated diarrhea, and weight loss visited the Digestive Disease Department of Nagoya City University Hospital on 19 December 2011. He was hospitalized and diagnosed with Crohn's colitis. His Crohn's Disease Activity Index (CDAI) was 415. Treatment by granulocyte apheresis, mesalazine, and adalimumab was started. His CDAI was 314 on 30 December and 215 on 5 January. A colonoscopic examination on 19 January showed almost complete remission in the transverse colon and marked remission in the rectum. Mesalazine therapy was stopped on 28 February, and the patient was instructed to self-inject 40 mg of adalimumab every other week. His CDAI was 50 on 10 April, indicating clinical remission. His last self-injection of adalimumab was on 24 April 2012, and he started taking 1 g of bovine lactoferrin (bLF) daily. His CDAI was 35 on 8 January 2013. He continued taking 1 g of bLF daily without any other treatment for Crohn's disease. Laboratory blood tests on 7 September 2015 showed no sign of disease recurrence, and a colonoscopic examination on 23 October 2015 showed almost complete mucosal healing. This case indicates that ingestion of bLF to maintain Crohn's disease in a remissive state should be further explored. [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf) is known for its physiologically pleiotropic properties. In this study, we investigated whether Lf affects glycemic regulation, including glucose absorption from the small intestine. Bovine Lf (bLf, 100 mg/kg body mass) was administered to rats by intraperitoneal injection before intravenous (intravenous glucose tolerance test, IVGTT) or oral glucose administration (oral glucose tolerance test, OGTT). With IVGTT, bLf pretreatment had no significant effect on plasma levels of glucose or insulin. With OGTT, the bLf treatment group tended to show lower plasma levels of glucose than the control group at and after the 15 min peak, and decreased levels of plasma glucose at 180 min. The change in plasma levels of insulin from 0 to 30 min was higher in the bLf treatment group than in the control group. Total plasma glucose-dependent insulinotropic polypeptide (GIP) was lowered at 60 min by the bLf treatment, while an immediate increase in total plasma glucagon-like peptide-1 (GLP-1) was observed within the bLf group undergoing OGTT. In addition, bLf was associated with an increase in the amount of glucose absorbed into the everted jejunum sac. These results suggest that Lf could suppress hyperglycemia, accompanied by elevated plasma levels of insulin via transiently accelerating GLP-1 secretion, and that Lf even enhances glucose absorption from the small intestine. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue including the benefits of lactoferrin (Lf) in preventing preterm delivery, antimicrobial activity of Lf and the role of bovine Lf in treating bovine mastitis.