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Background: Lactoferrin (bLF) is an iron-binding multifunctional protein that is abundant in milk. In mice, it inhibits catechol-O-methyltransferase (COMT) activity and increases blood levodopa levels. However, the clinical effects are unknown. Objective: The objective of this study was to determine the effect of bLF on the kinetics of levodopa in blood. Design: The effects of the concomitant administration of a combined formulation of levodopa and an aromatic amino acid decarboxylase inhibitor and bLF on the concentration of levodopa in blood and its metabolism were assessed in eight healthy subjects. In addition, we analyzed the association with clinical factors and evaluated whether clinical factors affected the COMT inhibitory activity of bLF in vitro. Results: Although not statistically significant, the peak plasma concentration (Cmax) of levodopa increased by 18.5%. From the results of the stratified analysis of total cholesterol, a relationship with ΔCmax was predicted. Therefore, bLF was reacted with cholesterol in the presence of lecithin and sodium deoxycholate in vitro to evaluate COMT inhibitory activity, and an increase in inhibitory activity was observed. By contrast, the ester compound cholesteryl oleate had no effect. The inhibitory activity of free fatty acids, which are known to interact with bLF, was also enhanced. Conclusion: The COMT inhibitory activity of bLF is not effective in elevating blood levodopa levels. However, in humans with high lipid levels, such as cholesterol, interactions may enhance the inhibitory effect, resulting in the enhanced absorption of levodopa. Trial registration: ID, UMIN000026787, registered 30 March 2017; URL, Trial registration: UMIN Japan identifier: UMIN000026787 [ABSTRACT FROM AUTHOR]

Human noroviruses cause significant morbidity and mortality worldwide, but lack approved antivirals or vaccines to treat or prevent infections. 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. Lactoferrin is an iron-binding glycoprotein found in the milk of most mammals, with broad spectrum antimicrobial activities, including against the related murine norovirus in cell culture. In a Japanese clinical trial, ingestion of lactoferrin reduced the incidence of infectious gastroenteritis in the participants. Because human noroviruses were the most common cause of gastroenteritis in Japan during the clinical trial period, we sought to determine whether lactoferrin could inhibit infection with human norovirus. Our study, using a B cell culture model, demonstrates that lactoferrin reduces human norovirus infection. The mechanism of antiviral action is likely indirect and may involve the induction of innate interferon responses. Therefore, future studies are warranted to test the antiviral efficacy of lactoferrin against human norovirus infection in patients. [ABSTRACT FROM AUTHOR]

Donor human milk (DHM) is the second-best nutrition for preterm infants when their own mother's milk is unavailable. The nutrient content of human milk is influenced by various factors, including gestational and postpartum age, but there are no data regarding DHM composition in Japan. The aim of this study was to determine the protein and immune component content of DHM in Japan and to elucidate the effects of gestational and postpartum age on nutrient composition. From September 2021 to May 2022, 134 DHM samples were collected from 92 mothers of preterm and term infants. Protein concentrations in preterm DHM ( n = 41) and term DHM ( n = 93) were analyzed using a Miris Human Milk Analyzer. The concentrations of secretory immunoglobulin A (sIgA) and lactoferrin, major immune components, were measured using enzyme-linked immunosorbent assays. Preterm DHM exhibited higher protein content than term DHM (1.2 g/dL and 1.0 g/dL, respectively, p < 0.001), whereas sIgA content was higher in term DHM than in preterm DHM (110 μg/mL and 68.4 μg/mL, respectively, p < 0.001). Gestational age was negatively correlated with protein levels and positively correlated with sIgA and lactoferrin levels. Furthermore, a negative correlation was found between postpartum week and protein, sIgA, and lactoferrin concentrations. Our data suggest that gestational and postpartum age affects protein, sIgA, and lactoferrin concentrations in DHM. These results indicate the importance of nutritional analysis for the appropriate use of DHM in preterm infants.

Various antimicrobial components, such as lactoferrin, S100 calcium-binding protein A7 (S100A7), and IgA, produced by epithelial cells and leukocytes in lactating mammary glands are important for host defense against invading pathogens. Increase in milking frequency enhances milk yield in ruminants and implies an increase in frequency of teat stimulation. However, the influence of frequent teat stimulation on the production of antimicrobial components remains unclear. In this study, we investigated the effect of frequent teat stimulation, with and without milk removal, on the lactoferrin, S100A7, and IgA concentrations in milk of lactating Shiba goats in Japan. The lactoferrin, S100A7, and IgA concentrations in milk were measured using ELISA. We found that lactoferrin concentration decreased by frequent teat stimulation with milk removal, although concentrations of IgA and S100A7 increased. Frequent teat stimulation without milk removal also altered the lactoferrin, IgA, and S100A7 concentrations. Furthermore, frequent teat stimulation increased IL-22 concentration, which has been reported to upregulate S100A7 production in cultured human keratinocytes. Thus, these findings indicate that frequent teat stimulation, with or without milk removal, affects antimicrobial components in milk and may be useful for the prevention and treatment of mastitis in ruminants. [ABSTRACT FROM AUTHOR]

Purpose: Orally administered bovine lactoferrin (bLF) exerts an anti-inflammatory effect on hepatitis and colitis animal models. To investigate the mechanism underlying the action of bLF, we explored the expression of inflammation-related factors in the intestine of a hepatitis mouse model after the oral administration of bLF and in several human intestinal cell lines treated with bLF. Methods: The effects of bLF on the expression of interleukin-11 (IL-11) and bone morphogenetic protein 2 (BMP2) in the intestinal mucosa of a hepatitis mouse model as well as in cell cultures of human intestinal epithelial cells, myofibroblasts, and monocytes were examined using the real-time reverse transcription polymerase chain reaction. Epithelial cells and myofibroblasts were also cocultured using transwells. bLF transport, and IL-11 and BMP2 induction, as well as the interactions between the two cell types, were then analyzed after bLF treatment. Results: In vivo, oral bLF administration increased the production of IL-11 and BMP2 in intestinal specimens. In vitro, bLF only stimulated the production of IL-11 in human intestinal myofibroblasts; i.e., it had no effect on BMP2 production in any cell type. In the transwell cocultures, bLF passed through the epithelium and directly stimulated IL-11 production in the myofibroblasts on the basolateral side. The IL-11 produced in the myofibroblasts subsequently acted protectively on the epithelial cells of the coculture. Conclusions: bLF upregulated the activity of anti-inflammatory factors, such as IL-11, in the intestine of a hepatitis mouse model and human intestinal myofibroblasts. [ABSTRACT FROM AUTHOR]

ntineutrophil cytoplasmic antibodies (ANCAs) against myeloperoxidase (MPO), proteinase 3 (PR-3), lactoferrin (LF), cathepsin G (CG) and elastase (EL) were determined to investigate whether the presence of ANCAs is closely related to extra-articular manifestations in Japanese patients with rheumatoid arthritis (RA). Antibodies against MPO, PR-3, LF, CG and EL were determined in sera from 125 patients with RA and 83 sera from patients with other rheumatic diseases by enzyme-linked immunosorbent assay. Clinical manifestations and laboratory parameters of the patients were studied from medical records. Thirty of the 125 (24.0%) RA patients were positive for ANCAs for at least one of these 5 ANCA antigens. Among the 5 ANCAs, anti-LF antibody (anti-LF) (16.8%) was most commonly observed in patients with RA. A higher joint score (JS) and an elevated ESR were demonstrated in ANCA-positive RA patients compared to those of ANCA-negative patients (40.8 ± 43.3, 24.3 ± 26.2, p < 0.05, 44.4 ± 22.4, 28.9 ± 23.6, p < 0.05, respectively). No statistical differences in the presence of interstitial pneumonia, cutaneous vasculitis, rheumatoid nodules and mononeuropathy multiplex were observed between ANCA-positive and ANCA-negative patients. The presence of anti-LF is expected to be of pathological relevance, as the action of anti-LF towards LF results in the inhibition of the anti-inflammatory activity of LF. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of lactoferrin (LF) on infectious diseases in Japanese summer., Methods: An intake of placebo, 200 mg, or 600 mg of LF were administered to healthy adults in Kyushu University of Health and Welfare for 12 weeks in a randomized, double-blinded, placebo-controlled parallel-group comparative trial. The primary endpoints were the prevalence and duration of infectious diseases and changes in immune parameters., Results: Three hundred and ten subjects were randomized (placebo, n = 104; 200 mg, n = 103; 600 mg, n = 103). Twenty subjects were lost to the follow-up, leaving 290 for a full analysis set (n = 99; n = 95; n = 96). The duration (day) of total infectious diseases was shorter in the 200 mg group (2.0, p = 0.045) and 600 mg group (2.0, p = 0.010) than in the placebo group (3.0). The duration of summer colds was shorter in the 600 mg group (2.0, p = 0.036) than in the placebo group (3.0). No significant differences were observed in the prevalence of infectious diseases or changes in immune parameters. In exploratory investigations, changes in the neutrophil phagocytic capacity, cortisol concentrations, and T score of "Vigor/Activity" in the Profile of Mood States 2 were greater in the 600 mg group than in the placebo group, when analysis was done on the lower half groups at the baseline. Adverse events were similar in each group and none had a causal relationship with the intake of the test foods., Conclusions: In summer, the intake of LF attenuates infectious diseases, including summer colds., Competing Interests: Declaration of Competing Interest HO, HW, MT, KY, and FA are employees of Morinaga Milk Industry. CS, HY, TS, and MK declare no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

This study investigated the preventive effects of lactoferrin (LF) on subjective acute gastrointestinal symptoms during the winter in a randomized, double-blinded, placebo-controlled parallel-group comparative trial. The eligible subjects were healthy adults working at kindergartens and nursery schools. We randomized the subjects to the Placebo group (0 mg/day), the Low LF group (200 mg/day), and the High LF group (600 mg/day) for 12 weeks. The prevalence of acute gastrointestinal symptoms was significantly lower in the High LF (13/112 vs. 26/116; p = 0.030) and the Low LF (13/107 vs. 26/116; p = 0.040) groups than in the Placebo group. The adjusted odds ratio for the prevalence of acute gastrointestinal symptoms was 2.78 (95% CI: 1.19-6.47) in the Placebo group compared with the High LF group. LF is useful to prevent acute gastrointestinal symptoms among childcare workers, who mainly consist of women.