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Lactoferrin (LF) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to determine the effect of bovine lactoferrin (bLF) in the prevention of SARS-CoV-2 infection in health care personnel. A randomized, double-blinded, placebo-controlled clinical trial was conducted in two tertiary hospitals that provide care to patients with SARS-CoV-2 infection in Lima, Peru. Daily supplementation with 600 mg of enteral bLF versus placebo for 90 days was compared. Participants were weekly screened for symptoms suggestive of SARS-CoV-2 infection and molecular testing was performed on suspected episodes. A serological test was obtained from all participants at the end of the intervention. The main outcome included symptomatic and asymptomatic cases. A sub-analysis explored the time to symptomatic infection. Secondary outcomes were the severity, frequency, and duration of symptomatic infection. The study was prematurely cancelled due to the availability of vaccines against SARS-CoV-2 in Peru. 209 participants were enrolled and randomized, 104 received bLF and 105 placebo. SARS-CoV-2 infection occurred in 11 (10.6%) participants assigned to bLF and in 9 (8.6%) participants assigned to placebo without significant differences (Incidence Rate Ratio = 1.23, 95%CI 0.51-3.06, p-value = 0.64). There was no significant effect of bLF on time to symptomatic infection (Hazard Ratio = 1.61, 95%CI 0.62-4.19, p-value = 0.3). There were no significant differences in secondary outcomes. A significant effect of bLF in preventing SARS-CoV-2 infection was not proven. Further studies are needed to assess the effect of bLF supplementation on SARS-CoV-2 infection.Clinical trial registration ClinicalTrials.gov Identifier: NCT04526821, https://clinicaltrials.gov/ct2/show/NCT04526821?term=LACTOFERRINcond=COVID-19cntry=PEcity=Limadraw=2rank=1 .

Contaminants in food have severely threatened human health, and appropriate antioxidants derived from food could reduce impairment risk. Lactoferrin from milk could control iron concentration in the blood to ameliorate oxidative stress, which is also required for sperm maturation, but the underlying mechanisms remain unclear. The present study used mice with spermatogenetic dysfunction caused by bisphenol A (BPA) and cadmium (Cd) to evaluate the ameliorative effects of lactoferrin and milk (bioactive substances). BPA (50 mg/kg) and Cd (1.6 mg/kg) caused severe damage to testis, including globally decreased germ cell counts, poor sperm quality, disordered apoptosis, oxidative stress, and autophagy; however bioactive substances comprehensively ameliorated spermatogenetic dysfunction via mitigating the increased levels of BAX/BCL2, LC3II/LC3I, and P62. AMPK was involved in autophagic regulation, while ERK1/2 inhibition attenuated the protective effects of lactoferrin, including restimulating apoptosis, oxidative stress, and arrested autophagic flux. Notably, P62 was consistently stimulated with different ERK1/2 inhibitors, which was ubiquitin-dependent. The study provides evidence for the alleviative effects of lactoferrin and milk in mice with spermatogenetic dysfunction through ERK1/2 mediated the ubiquitin-dependent degradation of P62. The involved signals and molecules could be identified as novel therapeutic targets for male infertility, which contributes to expanding LF's interests in research and application.

Lung injury occurring in the early stage of heat stroke (HS) leads to hypoxia and further aggravation of other organic damage. Lactoferrin (LF) is an iron binding protein with anti-inflammatory and antioxidant effects. This study focuses on the protection of preadministration of bovine lactoferrin (BLF) against lung injury in rats with HS. Sixty-four Sprague-Dawley male rats were divided into four groups randomly: control (CON)+phosphate-buffered saline (PBS) (

The development of novel wound dressings with highly effective antibacterial and accelerating wound healing properties has become the focus of current research. In this study, a novel and injectable lactoferrin (LF)/lithium magnesium silicate hydrogel (LMSH) was first synthesized through a simple electrostatic interaction method. The physical and biological properties are systematically characterized. The results show that the synthesized LF/LMSH has good antibacterial properties and biocompatibility. More importantly, it can effectively promote wound healing in the rat full-thickness skin wound model after 14 days post-operation, and the healing rate can reach 99.1 %, which is much higher than that of other groups. Meanwhile, histochemical and immunofluorescent staining confirm that the prepared injectable LF/LMSH has good pro-collagen deposition, pro-angiogenic and anti-inflammatory properties. The healed wounds present a consistently thickened epidermis with more follicular and glandular structures, indicating the great potential of the prepared material for wound management.

This study identifies promising potential of a novel and safer nanocombination of bovine milk lactoperoxidase (LPO) and lactoferrin (LF) to target breast cancer in vitro and in adult female albino rat model. Favorable selective anticancer effects of the prepared nanocombination were observed, in a dose-dependent manner, against both MCF-7 and MDA cell lines, sparing normal HFB-4 cells. The administration of LPO + LFNPs markedly improved the induced-breast cancer disorders, prolonged survival and reduced the values of serum TNF-α, IL1β, CD4

Iron is by far the most widespread and essential transition metal, possessing crucial biological functions for living systems. Despite chemical advantages, iron biology has forced organisms to face with some issues: ferric iron insolubility and ferrous-driven formation of toxic radicals. For these reasons, acquisition and transport of iron constitutes a formidable challenge for cells and organisms, which need to maintain adequate iron concentrations within a narrow range, allowing biological processes without triggering toxic effects. Higher organisms have evolved extracellular carrier proteins to acquire, transport and manage iron. In recent years, a renewed interest in iron biology has highlighted the role of iron-proteins dysregulation in the onset and/or exacerbation of different pathological conditions. However, to date, no resolutive therapy for iron disorders has been found. In this review, we outline the efficacy of Lactoferrin, a member of the transferrin family mainly secreted by exocrine glands and neutrophils, as a new emerging orchestrator of iron metabolism and homeostasis, able to counteract iron disorders associated to different pathologies, including iron deficiency and anemia of inflammation in blood, Parkinson and Alzheimer diseases in the brain and cystic fibrosis in the lung.

Background: The ESKAPE group of pathogens which comprise of multidrug resistant bacteria, namely Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species are the cause of deadly nosocomial infections all over the world. While these pathogens have developed robust strategies to resist most antibiotics, their ability to form biofilms is one of their most combative properties. Hence there is an urgent need to discover new antibacterial agents which could prevent or destroy the biofilms made by these bacteria. Though it has been established that lactoferrin (LF), a potent iron binding antibacterial, antifungal, and antiviral protein displays anti-biofilm properties, its mechanisms of action, in addition to its iron chelation property, still remains unclear. Objective: The binding and inhibition studies of LF with the enzyme Nucleoside diphosphate Kinase (NDK) and its elastase cleaved truncated 12 kDa fragment (12-NDK). Methods: The characterization studies of NDK and 12-NDK using florescence spectroscopy, dynamic light scattering, size exclusion chromatography and ADP-glo Kinase Assay. Inhibition studies of LF-NDK using ADP-glo kinase assay, Surface Plasmon Resonance and Biofilm inhibition studies. Results: NDK and 12-NDK were cloned, expressed and purified from Acinetobacter baumannii and Pseudomonas aeruginosa. The characterization studies revealed NDK and 12-NDK from both species are stable and functional. The inhibition studies of LF-NDK revealed stable binding and inhibition of kinase activity by LF. Conclusion: The binding and inhibition studies have shown that while LF binds with both the NDK and their truncated forms, it tends to have a higher binding affinity with the truncated 12 kDa fragments, resulting in their decreased kinase activity. This study essentially gives a new direction to the field of inhibition of biofilm formation, as it proves that LF has a novel mechanism of action in other than iron sequestration.

Background: Lactoferrin, an iron-binding glycoprotein, and calprotectin, a calcium binding protein, are sensitive markers of inflammation and their fecal levels increase during radiotherapy of prostate cancer patients. With this background, we analyzed mouthrinse calprotectin and lactoferrin levels of head- and neck-cancer patients before, during and after radiotherapy. Methods: Twenty cancer patients (mean age 55.85 ± 15.01, 80% male), who had been planned to undergo radiotherapy to the head and neck area, were included in this study. Mouthrinse samples were collected before radiotherapy, at the 3rd and 6th weeks of radiotherapy and 4 weeks after the radiotherapy. Mouthrinse samples were analyzed for calprotectin and lactoferrin using commercial ELISA kits. Results: Calprotectin levels increased significantly during radiotherapy (p = 0.022). Both markers, lactoferrin (p = 0.011) and calprotectin (p = 0.006), decreased significantly after the treatment. Conclusions: Present study results may suggest that the elevations in calprotectin and lactoferrin levels during radiotherapy reflect the increased and emerging inflammatory environment in the oral cavity, thus may increase the risk of periodontal disease initiation or progression.

We present a mass spectral library-based method for analyzing site-specific N-linked protein glycosylation. Its operation and utility are illustrated by applying it to both newly measured and available proteomics data of human milk glycoproteins. It generates two varieties of mass spectral libraries. One contains glycopeptide abundance distribution spectra (GADS). The other contains tandem mass spectra of the underlying glycopeptides. Both originate from identified glycopeptides in proteolytic digests of human milk and purified glycoproteins, which include tenascin, lactoferrin, and several antibodies. Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. These were acquired by higher-energy (stepped) collision dissociation fragmentation followed by ion-trap fragmentation. Spectra are annotated using MS_Piano, recently reported annotation software. This data, with extensions of a widely used spectral library search and display software, provides accessible mass spectral libraries.

Recent research has shown that lactoferrin indirectly suppresses osteoclastogenesis by affecting osteoblasts and periodontal ligament fibroblasts. However, the mechanism by which lactoferrin directly affects osteoclastogenesis is yet to be reported. Therefore, this study examined the direct effects of lactoferrin on RANKL-induced osteoclast differentiation of murine osteoclastic RAW 264.7 cells. The number of osteoclasts was determined by counting the number of cells positive for tartrate-resistant acid phosphatase staining. The effect of lactoferrin on the number of osteoclasts was measured, and the effect on the mRNA expression of osteoclast differentiation markers was assayed using real-time PCR. Lactoferrin decreased the number of osteoclasts (_2 nuclei) and large osteoclasts (_8 nuclei) in a dose-dependent manner without affecting the viability of RAW 264.7 cells. Additionally, it only mediated these effects within 48 h of culturing the RAW 264.7 cells with RANKL. Lactoferrin also significantly inhibited RANKL-induced mRNA expressions of osteoclastic differentiation genes, such as NFATc1, RANK, DC-STAMP, and OC-STAMP. Thus, these findings suggest that lactoferrin directly suppresses osteoclastogenesis within 48 h of culturing the RAW 264.7 cells with RANKL. Therefore, lactoferrin may be a novel and innovative therapy for treating bone diseases.

Tooth decay is one of the most common diseases that humans face during their lifetime. Streptococcus mutans is one of the most critical factors of early tooth decay. These bacteria may produce biofilms in the mouth, which are more resistant to antimicrobial agents. Streptococcus mutans may also demineralize tooth enamel by producing lactic acid. In this study, the effect of nanoliposomes containing lactoferrin at three different concentrations (1·5, 3 and 6 mg ml−1) on the biofilm formed by S. mutans was investigated. Nanoliposomes were prepared using the thin-layer hydration method. An active attachment model was used to evaluate biofilm and lactic acid production. The results showed that nano-encapsulated lactoferrin could reduce CFU of biofilm more effectively than free lactoferrin. Lactoferrin-containing nanoliposomes also significantly reduced lactic acid production by S. mutans. Therefore, nano-encapsulated lactoferrin may be used along with other dental caries control methods to increase anti-caries efficacy.

Lactoferrin, an iron-binding glycoprotein, plays a significant role in the innate immune system, with antibacterial, antivirial, antifungal, anticancer, antioxidant and immunomodulatory functions reported. It is worth emphasizing that not only the whole protein but also its derived fragments possess antimicrobial peptide (AMP) activity. Using AmpGram, a top-performing AMP classifier, we generated three novel human lactoferrin (hLF) fragments: hLF 397-412, hLF 448-464 and hLF 668-683, predicted with high probability as AMPs. For comparative studies, we included hLF 1-11, previously confirmed to kill some bacteria. With the four peptides, we treated three Gram-negative and three Gram-positive bacterial strains. Our results indicate that none of the three new lactoferrin fragments have antimicrobial properties for the bacteria tested, but hLF 1-11 was lethal against Pseudomonas aeruginosa. The addition of serine protease inhibitors with the hLF fragments did not enhance their activity, except for hLF 1-11 against P. aeruginosa, which MIC dropped from 128 to 64 µg/mL. Furthermore, we investigated the impact of EDTA with/without serine protease inhibitors and the hLF peptides on selected bacteria. We stress the importance of reporting non-AMP sequences for the development of next-generation AMP prediction models, which suffer from the lack of experimentally validated negative dataset for training and benchmarking.

Lactoferrin (LF) is a naturally present iron-binding globulin with the structural properties of an N-lobe strongly positively charged terminus and a cage-like structure of nano self-assembly encapsulation. These unique structural properties give it potential for development in the fields of electrostatic spinning, targeted delivery systems, and the gut-brain axis. This review will provide an overview of LF's unique structure, encapsulation, and targeted transport capabilities, as well as its applications in immunity and gut microbiota regulation. First, the microstructure of LF is summarized and compared with its homologous ferritin, revealing both structural and functional similarities and differences between them. Second, the electrostatic interactions of LF and its application in electrostatic spinning are summarized. Its positive charge properties can be applied to functional environmental protection packaging materials and to improving drug stability and antiviral effects, while electrostatic spinning can promote bone regeneration and anti-inflammatory effects. Then the nano self-assembly behavior of LF is exploited as a cage-like protein to encapsulate bioactive substances to construct functional targeted delivery systems for applications such as contrast agents, antibacterial dressings, anti-cancer therapy, and gene delivery. In addition, some covalent and noncovalent interactions of LF in the Maillard reaction and protein interactions and other topics are briefly discussed. Finally, LF may affect immunological function via controlling the gut microbiota. In conclusion, this paper reviews the research advances of LF in electrostatic spinning, nano self-assembly, and immune and gut microbiota regulation, aiming to provide a reference for its application in the food and pharmaceutical fields.

Growing evidence indicates that circulating lactoferrin (Lf) is implicated in peripheral cholesterol metabolism disorders. It has emerged that the distribution of Lf changes in astrocytes of aging brains and those exhibiting neurodegeneration; however, its physiological and/or pathological role remains unknown. Here, we demonstrate that astrocyte-specific knockout of Lf (designated cKO) led to decreased body weight and cognitive abnormalities during early life in mice. Accordingly, there was a reduction in neuronal outgrowth and synaptic structure in cKO mice. Importantly, Lf deficiency in the primary astrocytes led to decreased sterol regulatory element binding protein 2 (Srebp2) activation and cholesterol production, and cholesterol content in cKO mice and/or in astrocytes was restored by exogenous Lf or a Srebp2 agonist. Moreover, neuronal dendritic complexity and total dendritic length were decreased after culture with the culture medium of the primary astrocytes derived from cKO mice and that this decrease was reversed after cholesterol supplementation. Alternatively, these alterations were associated with an activation of AMP-activated protein kinase (AMPK) and inhibition of SREBP2 nuclear translocation. These data suggest that astrocytic Lf might directly or indirectly control in situ cholesterol synthesis, which may be implicated in neurodevelopment and several neurological diseases.

Background Bovine lactoferrin is increasingly being used as an ingredient in infant formula manufacture to enhance nutritional efficacy through the provision of immunoprotective, growth, and antimicrobial factors to the neonate. Objective To evaluate the analytical performance of an optical biosensor immunoassay for compliance with the method performance requirements described in SMPR 2020.005. Method Following dilution of the sample in buffer, an automated, label-free, real-time optical biosensor immunoassay was used in a direct assay format to quantitate bovine lactoferrin by its interaction with an immobilized anti-lactoferrin antibody. Quantitation was accomplished by the external standard technique with interpolation from a 4-parameter calibration regression. Results The analytical range (0–200 mg/hg), method detection limit (0.8 mg/hg), recovery (96.1–109.2%), and repeatability (1.0–5.3%) complied with the requirements given in the lactoferrin SMPR. The method was shown to be specific for native, intact lactoferrin; thermally denatured lactoferrin generated no measurable binding response. Conclusion The method described is suitable for the quantification of intact, undenatured lactoferrin in milk products, infant formulas (bovine milk protein-based, soy protein-based, and amino acid-based), and adult nutritionals and has been demonstrated to meet the performance requirements defined in SMPR 2020.005. Highlights A single-laboratory validation (SLV) of an automated biosensor immunoassay for the determination of intact, undenatured lactoferrin is described.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The objective of this review will be to evaluate the efficacy and safety of administering lactoferrin for the post‐operative management of term neonates, measured by the incidence of sepsis, mortality and duration of hospital stay. We aim to evaluate benefits and harms with the use of lactoferrin in individual gastrointestinal pathologies and specific lactoferrin product, if sufficient data are available.

Fisetin (FS) is considered a safer phytomedicine alternative to conventional chemotherapeutics for breast cancer treatment. Despite its surpassing therapeutic potential, its clinical utility is hampered by its low systemic bioavailability. Accordingly, as far as we are aware, this is the first study to develop lactoferrin-coated FS-loaded β-cyclodextrin nanosponges (LF-FS-NS) for targeted FS delivery to breast cancer. NS formation through cross-linking of β-cyclodextrin by diphenyl carbonate was confirmed by FTIR and XRD. The selected LF-FS-NS showed good colloidal properties (size 52.7 ± 7.2 nm, PDI < 0.3, and ζ-potential 24 mV), high loading efficiency (96 ± 0.3%), and sustained drug release of 26 % after 24 h. Morphological examination using SEM revealed the mesoporous spherical structure of the prepared nanosponges with a pore diameter of ~30 nm, which was further confirmed by surface area measurement. Additionally, LF-FS-NS enhanced FS oral and IP bioavailability (2.5- and 3.2-fold, respectively) compared to FS suspension in rats. Antitumor efficacy evaluation in vitro on MDA-MB-231 cells and in vivo on an Ehrlich ascites mouse model demonstrated significantly higher activity and targetability of LF-FS-NS (30 mg/kg) compared to the free drug and uncoated formulation. Consequently, LF-FS-NS could be addressed as a promising formulation for the effective management of breast cancer.

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.

Background: The New Global Economy is represented by a series of major features, such as the use of green energy, the reduction of the carbon footprint in all industrial and civil fields, as well as finding alternative food resources. Our main objective was the research of a sustainable food product with a special nutritional purpose in the vision of nutrivigilance, developed in Romania, as an adjuvant in the repair of gastric mucosa. Methods: The materials used in the research and development of the new food are the following: inulin, lactoferrin, sericin, and sodium bicarbonate. The new adjuvant food product in the repair of the gastric mucosa was added to certain foods in order to prevent the patients from being satiated by a single food from a sensory point of view. The resulting food products were organoleptically and physico-chemically analyzed. Results: The new food is sustainable and has versatile uses. It can be hydrated with water, non-carbonated drinks, mixed with cottage cheese, or with fruit puree and oatmeal. It is stable under normal storage conditions and microbiologically safe. Conclusions: Through its versatile use, the new food product for special nutritional conditions represents a worldwide novelty. Through the development of forestry for the cultivation of white or black mulberry (Morus alba and Morus nigra), the raising of silkworms (Bombyx mori), the processing of fibroin to obtain natural silk and the processing of sericin resulting as a residue in the textile industry, the new food product developed actively contribute to the global economy II.

An evaluation of the association between the concentrations of vitamin D-binding protein and lactoferrin in the plasma and peritoneal fluid may facilitate the elucidation of molecular mechanisms in endometriosis. Vitamin D-binding protein and lactoferrin concentrations were measured by ELISA in plasma and peritoneal fluid samples from 95 women with suspected endometriosis as classified by laparoscopy into groups with (n = 59) and without endometriosis (n = 36). There were no differences (p > 0.05) in the plasma and peritoneal fluid concentrations of vitamin D-binding protein and lactoferrin between women with and without endometriosis. In women with endometriosis, there was a significant correlation between plasma and peritoneal fluid vitamin D-binding protein concentrations (r = 0.821; p = 0.000), but there was no correlation between lactoferrin concentrations in those compartments (r = 0.049; p > 0.05). Furthermore, in endometriosis, lactoferrin was found to correlate poorly with vitamin D-binding protein (r= −0.236; p > 0.05) in plasma, while in the peritoneal fluid, the correlation between those proteins was significant (r = 0.399; p = 0.002). The characteristic properties of vitamin D-binding protein and lactoferrin and the associations between their plasma and peritoneal fluid concentrations found in women with endometriosis may provide a novel panel of markers to identify high-risk patients in need of further diagnostic measures.

A limited number of effective therapies are currently available to treat human coronavirus SARS-CoV-2 and other human coronaviruses, which are responsible for nearly a third of global cases of the common cold. The possibility of new emerging coronaviruses demands powerful new antiviral strategies. Lactoferrin is a well-known protein that possesses anti-inflammatory and immunomodulatory activities, and it has previously shown antiviral activity against several viruses, including SARS-CoV-2. To increase this antiviral activity, here we present bovine liposomal lactoferrin. Liposomal encapsulation of the compound was proven to increase permeability, bioavailability, and time release. In the present work, we compare the antiviral activity of free and liposomal bovine lactoferrin against HCoV229E and SARS-CoV-2 in vitro and in human primary bronchial epithelial cells, and we demonstrated that the liposomal form exerts a more potent antiviral activity than its free form at non-cytotoxic doses.

Biological macromolecules, especially therapeutic proteins, are delicate and highly sensitive to denaturation from stresses encountered during the manufacture of dosage forms. Thin-film freeze-drying (TFFD) and spray freeze-drying (SFD) are two processes used to convert liquid forms of protein into dry powders. In the production of inhalable dry powders that contain proteins, these potential stressors fall into three categories based on their occurrence during the primary steps of the process: (1) droplet formation (e.g., the mechanism of droplet formation, including spray atomization), (2) freezing, and (3) frozen water removal (e.g., sublimation). This study compares the droplet formation mechanism used in TFFD and SFD by investigating the effects of spraying on the stability of proteins, using lactoferrin as a model. This study considers various perspectives on the denaturation (e.g., conformation) of lactoferrin after subjecting the protein solution to the atomization process using a pneumatic two-fluid nozzle (employed in SFD) or a low-shear drop application through the nozzle. The surface activity of lactoferrin was examined to explore the interfacial adsorption tendency, diffusion, and denaturation process. Subsequently, this study also investigates the secondary and tertiary structure of lactoferrin and the quantification of monomers, oligomers, and, ultimately, aggregates. The spraying process affected the tertiary structure more negatively than the tightly woven secondary structure, resulting in the peak position corresponding to the tryptophan (Trp) residues red-shifting by 1.5 nm. This conformational change can either (a) be reversed at low concentrations via relaxation or (b) proceed to form irreversible aggregates at higher concentrations. Interestingly, when the sample was allowed to progress into micrometer-sized aggregates, such a dramatic change was not detected using methods such as size-exclusion chromatography, polyacrylamide gel electrophoresis, and dynamic light scattering at 173°. A more complete understanding of the heterogeneous protein sample was achieved only through a combination of 173 and 13° backward and forward scattering, a combination of derived count rate measurements, and microflow imaging (MFI). After studying the impact of droplet formation mechanisms on aggregation tendency of lactoferrin, we further investigated two additional model proteins with different surface activity: bovine IgG (serving as a non surface-active negative reference), and β-galactosidase (another surface-active protein). The results corroborated the lactoferrin findings that spray-atomization-related stress-induced protein aggregation was much more pronounced for proteins that are surface active (lactoferrin and β-galactosidase), but it was minimal for non-surface-active protein (bovine IgG). Finally, compared to the low-shear dripping used in the TFFD process, lactoferrin underwent a relatively fast conformational change upon exposure to the high air-water interface of the two-fluid atomization nozzle used in the SFD process as compared to the low shear dripping used in the TFFD process. The interfacial-induced denaturation that occurred during spraying was governed primarily by the size of the atomized droplets, regardless of the duration of exposure to air. The percentage of denatured protein population and associated activity loss, in the case of β-galactosidase, was determined to range from 2 to 10% depending on the air-flow rate of the spraying process.

The main objective of this review was to state a hypothetical mechanism of the antitoxic effect of lactoferrin (Lf) on embryos exposed to bisphenol A (BPA). On this basis, it is possible to suggest Lf as a potential protective health component before conception upon toxic effects and viral infections.The narrative review was performed using systematic review methods to identify relevant literature. The resources required for this study were obtained by searching the electronic database PubMed (MEDLINE). Articles were searched using the keywords "BPA," "lactoferrin," "DNA-methylation," "epigenetic," "mammals," "human," and "mouse." The inclusion criteria were as follows: (a) primary or original research; (b) study of epigenetic modification; and (c) study focuses on early mammalian development.Presented data demonstrate that Lf can modulate epigenetical characteristic, such as DNA methylation and reactive oxygen species (ROS), and, thereby, may serve as a potential readily available pharmaceutical product.Suggested hypothesis is based on the important interrelated role of changes in epigenetic modifications and oxidative stress in early embryogenesis under the influence of BPA and virus infection as a cause of the development of pathologies in the adult organism.

The present study evaluated the growth performance, digestive enzyme activity, non-specific immunity, immunity and growth genes in Penaeus vannamei fed diets supplemented with Bovine lactoferricin (the basal diet without Bovine lactoferricin, the control; 1.0‰ Bovine lactoferricin，LCB1; 1.5‰ Bovine lactoferricin，LCB1.5; 2.0‰ Bovine lactoferricin, LCB2; 2.5‰ Bovine lactoferricin, LCB2.5) for 56 days. The feeding trial showed that the final weight, weight gain rate, and specific growth rate of the shrimp were improved significantly, while the feed conversion ratio was reduced significantly in the LCB1.5 group compared to the control (P 0.05). The challenge test of Vibrio parahaemolyticus showed that the cumulative mortalities of shrimp in the LCB1.5, LCB2 and LCB2.5 groups were significantly lower than that in the control (P 0.05). Compared with the control, Lipase and Trypsin activities in the hepatopancreas of LCB1.5 and LCB2 groups were significantly enhanced (P 0.05). Compared with the control, alkaline phosphatase, acid phosphatase activities in the hepatopancreas and the relative expression levels of Relish, Toll, JAK, STAT, TOR, Raptor, 4E-BP, eIF4E1α, eIF4E2 genes in the hepatopancreas of LCB1.5, LCB2 and LCB2.5 groups were all significantly enhanced (P 0.05). These results suggested that dietary Bovine lactoferricin could improve the growth performance, digestive capacity and immune responses of shrimp. When resistance against Vibrio parahaemolyticus in shrimp is considered, high dosage of Bovine lactoferricin showed a better effect than low dosage of Bovine lactoferricin. However, high dosage of Bovine lactoferricin can have a negative impact on the growth performance of shrimp. Considering collectively the above, Bovine lactoferricin could improve the growth performance, digestive enzymes activities, immune responses and disease resistance of P. vannamei.

Nanostructured lipid carriers (NLC) are novel lipidic nanosystems that provide significant improvements in terms of high drug loading capacity and controlled drug release. The purpose of the present work was based on the design, development, and physicochemical characterization of lactoferrin-loaded NLCs as a new therapeutic alternative for the keratoconus treatment. Lactoferrin-loaded NLCs were successfully prepared by a double emulsion/solvent evaporation method. The resultant NLC were assessed in terms of particle size, size distribution, surface charge, morphology, encapsulation efficiency (EE), loading capacity (LC), stability, cytotoxicity, in vitro release, and ocular surface retention. Resulting data showed a size of 119.45 ± 11.44 nm, a 0.151 ± 0.045 PDI value and a surface charge of −17.50 ± 2.53 mV. Besides, high EE and LC values were obtained (up to 75%). The in vitro release study demonstrated a lactoferrin controlled release pattern. NLCs were also stable, non-toxic and show mucoadhesive properties. Thus, a consistent preclinical base was obtained, where NLC may be considered as a potential controlled release novel drug delivery system of lactoferrin for the keratoconus treatment RVF and XGO acknowledge the financial support of the FIDIS (Health Research Institute of Santiago de Compostela Foundation). SEM and TEM analysis were feasible thanks to the Electronic and Confocal Microscopy Unit of the University of Santiago de Compostela (USC) (CACTUS, Spain). The work was partially supported by the Spanish Ministry of Science, Innovation and Universities (RTI2018-099597-B- 100) SI

Lactoferrin (LF) is a milk protein that may be an interesting candidate for the antidiabetic properties of milk due to its well-documented bioactivity and implication in diabetes. Here, we investigated the functional action of LF purified from camel and bovine milk (cLF, bLF) on insulin receptors (IR) and their pharmacology and signaling in hepatocarcinoma (HepG2) and human embryonic kidney (HEK293) cells. For this, we examined IR activation by bioluminescence resonance energy transfer (BRET) technology and the phosphorylation of its key downstream signaling kinases by western blot. The purified cLF and bLF induced phosphorylation of IR, AKT, and ERK1/2 in HepG2 and HEK293 cells. The BRET assays in HEK293 cells confirm the pharmacological action of cLF and bLF on IR, with a possible allosteric mode of action. This reveals for the first time the bioactivity of LF toward IR function, indicating it as a potential bioactive protein behind the antidiabetic properties of camel milk.

One trend of the modern world is the search for new biologically active substances based on renewable resources. Milk proteins can be a solution for such purposes as they have been known for a long time as compounds that can be used for the manufacturing of multiple food and non-food products. Thus, the goal of the work was to investigate the parameters of Zn-bovine lactoferrin (bLTF) interactions, which enables the synthesis of Zn-rich protein complexes. Zinc-bLTF complexes can be used as food additives or wound-healing agents. Methodology of the study included bLTF characterization by sodium dodecyl sulfate-PAGE, MALDI-TOF, and MALDI-TOF/TOF mass spectrometry as well Zn-bLTF interactions by attenuated total reflection-Fourier-transform infrared, Raman spectroscopy, scanning and transmission microscopy, and zeta potential measurements. The obtained results revealed that the factors that affect Zn-bLTF interactions most significantly were found to be pH and ionic strength of the solution and, in particular, the concentration of Zn

Orally absorbable gold nanoparticles (AuNP) having cancer ablation therapy is strongly demanded to treat glioblastoma multiforme (GBM) for patients with its highest incidence rate. Here, we develop a milk protein lactoferrin-conjugated AuNP for its oral absorption and targeting to the GBM through the interaction between lactoferrin (Lf) and lactoferrin receptor (LfR) that is highly expressed in the intestine, blood-brain barrier and GBM. For stability and long circulation of AuNP, glutathione and polyethylene glycol (PEG) is introduced, which is called to Lf-PEG-AuNP. When Lf-PEG-AuNP are orally administered to orthotopic GBM-bearing mice, 11-fold and 8-fold higher concentrations of AuNP are measured in bloodstreams and GBM in the brain, respectively, compared with unconjugated-AuNP. Therefore, orally administered Lf-PEG-AuNP exhibit an outstanding temperature rise in GBM by irradiating laser and significantly reduce tumor volume. Collectively, we suggest that the Lf-PEG-AuNP can fundamentally target GBM in the brain through oral absorption, and that its efficient photothermal therapy is possible., Graphical abstract Graphical abstract text: Lf-PEG-AuNP has strong absorption capacity at the GI tract and efficient accumulation on the GBM due to LfR-mediated transport. Therefore, external 532 nm NIR laser irradiation on the specific GBM region, resulted about 60 °C heat generation. The successful PTT treatment of Lf-PEG-AuNP, decreased GBM volume by 80% and the apoptosis and necrosis were observed at the treated site.Image 1, Highlights • Glioblastoma multiforme is notoriously malignant, especially in the elderly. • Oral formulation of therapeutic drugs reduce stress during administration. • Milk protein Lactoferrin (Lf) enables oral absorption and GBM targeting of drug. • Lf receptor-mediated transportation of Lf-shelled gold nanoparticle was verified. • Photothermal therapy of gold nanoparticle targeting GBM confers therapeutic effect.

Objective: This study compared the concentration of salivary lactoferrin in patients with and without chronic periodontitis and investigated correlations with clinical variables of the disease. Methods: The study included 102 participants (51 cases and 51 controls) who presented at the Periodontology Clinic of University of Benin Teaching Hospital and met the selection criteria of ‘4mm and above’ periodontal probing depths (PPD) and positive bleeding on probing (BOP) using community periodontal index (CPI) probe. Healthy participants (controls) were patients that had PPD less than or equal to 3mm, absence of BOP and simplified oral hygiene index (OHI-S) not more than 1.2. Baseline OHI-S and CPI scores were recorded. Saliva samples were collected and analyzed using enzyme-linked immunosorbent assay. All data were analyzed with the Statistical Package for Social Sciences (SPSS) version 22.0. Results: There was a statistically significant difference between the mean (SD) lactoferrin concentration of control participants 5.27(0.59) mg/l and case participants 6.74(0.61) mg/l (p

Previously we have shown that lactoferrin (LTF), a protein of secondary neutrophilic granules, can be efficiently modified by hypohalous acids (HOCl and HOBr), which are produced at high concentrations during inflammation and oxidative/halogenative stress by myeloperoxidase, an enzyme of azurophilic neutrophilic granules. Here we compared the effects of recombinant human lactoferrin (rhLTF) and its halogenated derivatives (rhLTF-Cl and rhLTF-Br) on functional responses of neutrophils. Our results demonstrated that after halogenative modification, rhLTF lost its ability to induce mobilization of intracellular calcium, actin cytoskeleton reorganization, and morphological changes in human neutrophils. Moreover, both forms of the halogenated rhLTF prevented binding of N-acetylglucosamine-specific plant lectin Triticum vulgaris agglutinin (WGA) to neutrophils and, in contrast to native rhLTF, inhibited respiratory burst of neutrophils induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine and by two plant lectins (WGA and PHA-L). However, we observed no differences between the effects of rhLTF, rhLTF-Cl, and rhLTF-Br on respiratory burst of neutrophils induced by phorbol 12-myristate 13-acetate (PMA), digitonin, and number of plant lectins with different glycan-binding specificity. Furthermore, all rhLTF forms interfered with PMA- and ionomycin-induced formation of neutrophil extracellular traps. Thus, halogenative modification of LTF is one of the mechanisms involved in modulating a variety of signaling pathways in neutrophils to control their pro-inflammatory activity.

Lactoferrin (Lf) is a natural iron-binding globular glycoprotein, present mainly in milk. It maintains human health through its multifunctional activities, including immunomodulation, iron metabolism, and antioxidant and prebiotic efficacy. It also shows anti-microbial, anti-fungal, and anti-viral activities against a broad spectrum of viruses, including SARS-CoV-2 that causes COVID-19. In addition, several investigations established that Lf is involved in bone metabolism, neural development, and metabolic disorders. In this review, we summarize the

Kidney disease is becoming a global public health issue. Acute kidney injury (AKI) and chronic kidney disease (CKD) have serious adverse health outcomes. However, there is no effective therapy to treat these diseases. Lactoferrin (LF), a multi-functional glycoprotein, is protective against various pathophysiological conditions in various disease models. LF shows protective effects against AKI and CKD. LF reduces markers related to inflammation, oxidative stress, apoptosis, and kidney fibrosis, and induces autophagy and mitochondrial biogenesis in the kidney. Although there are no clinical trials of LF to treat kidney disease, several clinical trials and studies on LF-based drug development are ongoing. In this review, we discussed the possible kidney protective mechanisms of LF, as well as the pharmacological and therapeutic advances. The evidence suggests that LF may become a potent pharmacological agent to treat kidney diseases.

In situations of intestinal dysbiosis caused by taking antibiotics, lactoferrin, a bovine milk protein, improves intestinal health by modulating the intestinal microbiota and the immune system positively and can be used in functional foods.

Aging is frequently accompanied by various types of physiological deterioration, which increases the risk of human pathologies. Global public health efforts to increase human lifespan has been increasingly focusing on lowering the risk of incidences of aging-related disease, such as diabetes, neurodegenerative diseases, cardiovascular disease and cancers. Dietary interventions is a promising approach to maintain human health during aging. Lactoferrin (LF) is known for its physiologically pleiotropic properties. Anti-aging interventions of LF have proven to be safe and effective for various pharmacological activities such as antioxidants, anti-cellular senescence, anti-inflammation, and anti-carcinogenic. As well as the pivotal role of LF on the modulating of major signaling pathways that influence longevity of organisms. Thus, LF is expected to be able to attenuate the process of aging and greatly ameliorate its effects.

Combined use of various antimicrobial peptides (AMPs) with enzymes that hydrolyze the signaling molecules of the resistance mechanism of various microorganisms, quorum sensing (QS), to obtain effective antimicrobials is one of the leading approaches in solving the antimicrobial resistance problem. Our study investigates the lactoferrin-derived AMPs, lactoferricin (Lfcin), lactoferampin and Lf(1-11), as potential partners for combination with enzymes hydrolyzing lactone-containing QS molecules, the hexahistidine-containing organophosphorus hydrolase (His6-OPH) and penicillin acylase, to obtain effective antimicrobial agents with a scope of practical application. The possibility of the effective combination of selected AMPs and enzymes was first investigated in silico using molecular docking method. Based on the computationally obtained results, His6-OPH/Lfcin combination was selected as the most suitable for further research. The study of physical–chemical characteristics of His6-OPH/Lfcin combination revealed the stabilization of enzymatic activity. A notable increase in the catalytic efficiency of action of His6-OPH in combination with Lfcin in the hydrolysis of paraoxon, N-(3-oxo-dodecanoyl)-homoserine lactone and zearalenone used as substrates was established. Antimicrobial efficiency of His6-OPH/Lfcin combination was determined against various microorganisms (bacteria and yeasts) and its improvement was observed as compared to AMP without enzyme. Thus, our findings demonstrate that His6-OPH/Lfcin combination is a promising antimicrobial agent for practical application.

In this work, the effect of an alginate-based coating loaded with hydroxyapatite/lactoferrin/quercetin (HA/LACTO-QUE) complexes during the storage of pork meat was evaluated. FT-IR spectra of HA/LACTO-QUE complexes confirmed the adsorption of QUE and LACTO into HA crystals showing the characteristic peaks of both active compounds. The kinetic releases of QUE and LACTO from coatings in an aqueous medium pointed out a faster release of LACTO than QUE. The activated alginate-based coating showed a high capability to slow down the growth of total viable bacterial count, psychotropic bacteria count, Pseudomonas spp. and Enterobacteriaceae during 15 days at 4 °C, as well as the production of the total volatile basic nitrogen. Positive effects were found for maintaining the hardness and water-holding capacity of pork meat samples coated with the activated edible coatings. Sensory evaluation results demonstrated that the active alginate-based coating was effective to preserve the colour and odour of fresh pork meat with overall acceptability up to the end of storage time.

Deoxynivalenol (DON) is among the most prevalent contaminants in cereal crops and has been demonstrated to impair male spermatogenesis and induce oxidative stress, testicular apoptosis, and disruption of the blood–testis barrier (BTB). Lactoferrin (LF) is an iron-binding glycoprotein with multifunctions including anti-inflammation and antioxidation. Thus, this study aimed to investigate the effects of LF on the spermatogenesis and integrity of the BTB in DON-exposed mice. Thirty-two male mice were allotted to four groups for a 35-day feeding period: vehicle (basal diet), DON (12 mg/kg), LF (10 mg/d, p.o.), and DON + LF. The results showed that DON induced vacuolization of the spermatogenic epithelium, broke the adhesion junction between Sertoli cells and spermatids established by N-cadherin and induced testicular oxidative stress. LF administration restored sperm production, attenuated the DON-induced oxidative stress and reduced the breakages in adhesion junction. DON exposure enhanced the protein expression of occludin. Transcriptional profiling of the testis observed a disturbance in the expression profiles of cell adhesion and inflammatory response genes, and LF administration reversed these gene expressions. Furthermore, down-regulated signaling pathways, including the apical junction, TNFα signaling via NF-κB, and TGF-β in the DON group were observed. These were restored by LF. Enrichment analysis between DON + LF group and vehicle also confirmed the absence of these pathways. These findings indicated that LF eliminated the DON-induced detriment to spermatogenesis and cell connections between Sertoli cells and spermatids via improving antioxidant capacity and modifying the inflammatory response and cell adhesion genes.

The rapid rollout of COVID-19 vaccines in 2021 sparked general optimism toward controlling the severe form of the disease, preventing hospitalizations and COVID-19-associated mortality, and the transmissibility of SARS-CoV-2 infection [...]

The Trans-Activator of Transcription (Tat) of Human Immunodeficiency Virus (HIV-1) is involved in virus replication and infection and can promote oxidative stress in human astroglial cells. In response, host cells activate transcription of antioxidant genes, including a subunit of System Xc− cystine/glutamate antiporter which, in turn, can trigger glutamate-mediated excitotoxicity. Here, we present data on the efficacy of bovine Lactoferrin (bLf), both in its native (Nat-bLf) and iron-saturated (Holo-bLf) forms, in counteracting oxidative stress in U373 human astroglial cells constitutively expressing the viral protein (U373-Tat). Our results show that, dependent on iron saturation, both Nat-bLf and Holo-bLf can boost host antioxidant response by up-regulating System Xc− and the cell iron exporter Ferroportin via the Nuclear factor erythroid 2-related factor (Nrf2) pathway, thus reducing Reactive Oxygen Species (ROS)-mediated lipid peroxidation and DNA damage in astrocytes. In U373-Tat cells, both forms of bLf restore the physiological internalization of Transferrin (Tf) Receptor 1, the molecular gate for Tf-bound iron uptake. The involvement of astrocytic antioxidant response in Tat-mediated neurotoxicity was evaluated in co-cultures of U373-Tat with human neuronal SH-SY5Y cells. The results show that the Holo-bLf exacerbates Tat-induced excitotoxicity on SH-SY5Y, which is directly dependent on System-Xc− upregulation, thus highlighting the mechanistic role of iron in the biological activities of the glycoprotein.

Background: Breast milk, with its complex, individual and over time adapting composition, is considered the optimal source of nutrition for infants during the first months of life. Two possible contributing factors to the benefits of breastfeeding compared to infant formula-feeding are the differences in iron and lactoferrin (Lf) concentrations between breast milk and infant formula. The overall purpose of the LIME (a Swedish acronym) study was to add knowledge on how to reduce the gap in health and development between breastfed and formula-fed infants. The aim of this double-blinded controlled trial, and doctoral thesis, was to investigate how added bovine lactoferrin and reduced iron concentration in infant formula affect health and development. Methods: Recruitment took place from June 2014 to June 2018. With equal gender distribution, healthy term Swedish formula-fed infants (n=180) were randomly assigned, from 6 weeks to 6 months of age, to receive a low iron formula (2 mg/L) with bovine Lf (1.0 g/L) (Lf+, n=72), a low iron formula without Lf (Lf-, n=72) or a control standard formula with 8 mg/L iron and no Lf (CF, n=36). Additionally, 72 breastfed infants were recruited as a reference (BF) group. Blood samples were drawn at 4, 6, and 12 months. Primary outcomes were cytokine levels and iron status. Secondary outcomes were growth, gastrointestinal symptoms, infection-related morbidity and treatments, antibody response to vaccines and cognitive development. Findings: All explored outcomes were unaffected by Lf fortification and the two low iron groups (Lf+ and Lf-) were combined and compared to the CF group. At 6 months of age the TGF-β2 levels were lower among the low iron groups and more similar to the BF infants. No other significant differences in cytokine levels were observed. There was a trend of lower geometric mean of ferritin at 4, 6, and 12 months for the combined low iron groups compared to the CF group (67.7 vs 88.7, 39.5 vs 50.9, and 20.5 vs 25.1 μg/L, respectively, p=0.054, p=0.056, and p=0.082). No similar trends or significant differences were found for any of the other iron status indicators, except for hepcidin at 12 months with lower levels in the low iron group compared to CF (37.8 vs 49.4 ng/mL, p=0.027). Overall, infants fed low iron formula had iron status indicators closer to the breastfed reference group and the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) was generally low with no significant differences among the intervention groups. There were no clinically relevant effects of the interventions on growth, gastrointestinal symptoms, infection-related morbidity, vaccine antibody response or neurocognitive development. In secondary analyses, the present study confirmed previous results of higher cognitive scores among breastfed infants compared to formula-fed and observed an unexpected lower IgG response to vaccines against Hib and Diphtheria. Conclusion: Adding bovine lactoferrin did not affect any of the clinical outcomes explored. Lowering infant formula iron concentration from 8 to 2 mg/L minimally reduced iron stores to levels closer to breastfed infants but did not increase the risk of ID/IDA during the first year of life. Consequently, 2 mg/L is a sufficient level of iron fortification during the first six months of life in a population with low risk of ID. Both adjustments are considered safe with no observed adverse effects.

OBJECTIVES: Compared to formula-fed infants, breastfed infants have a lower risk of infections. Two possible reasons for this are the presence of the anti-infective and anti-inflammatory protein lactoferrin and the lower level of iron in breast milk. We explored how adding bovine lactoferrin and reducing the iron concentration in infant formula affect immunology and risk of infections in healthy infants. METHODS: In a double-blind controlled trial, term formula-fed (FF) Swedish infants (n = 180) were randomized to receive, from 6 weeks to 6 months of age, a low-iron formula (2 mg/L) with added bovine lactoferrin (1.0 g/L) (Lf+; n = 72); low-iron formula with no added lactoferrin (Lf-; n = 72); and standard formula at 8 mg/L iron and no added lactoferrin (control formula [CF]; n = 36). Cytokines, infections, and infection related treatments were assessed until 12 months of age. RESULTS: No adverse effects were observed. There were no apparent effects on transforming growth factor beta (TGF-β)1, TGF-β2, tumor necrosis factor alfa (TNF-α) or interleukin2 (IL-2) at 4, 6, or 12 months, except of higher TGF-β2 at 6 months in the CF group in comparison to the low iron groups combined (P = 0.033). No significant differences in otitis, respiratory infections, gastroenteritis, or other monitored infections and treatments were detected for any of the study feeding groups during the first 6 months and only a few and diverging effects were observed between 6 and 12 months. CONCLUSIONS: Adding bovine lactoferrin and reducing iron from 8 to 2 mg/L in infant formula was safe. No clinically relevant effects on cytokines or infection related morbidity were observed in this well-nourished and healthy population.

Lactoferrin (Lf) can attenuate alcoholic liver injury (ALI) in male mice; however, the effects of Lf on acute ALI in female mice are still unknown. Female C57BL/6J mice were randomly divided into four groups and fed with different diets for 4 weeks: an AIN-93G diet for control (CON) and ethanol (EtOH) groups; an AIN-93G diet with 0.4 and 4% casein replaced by Lf for low-dose Lf (LLf) and high-dose Lf (HLf) groups. Acute ALI was induced by intragastric administration of ethanol (4.8 g/kgbw) every 12 h continuously for three times. HLf had obvious alleviating effects on acute ALI. Lf pretreatment did not affect hepatic alcohol metabolism key enzymes. Meanwhile, the ethanol-induced hepatic reactive oxygen species level increase was not ameliorated by Lf. Metabolomics and bioinformatics analysis results suggested an important role of redox-stress response capacity (RRC). Western blots showed HLf-promoted AKT and AMP-activated protein kinase activations and upregulated Nrf2 and LC3-II expressions, which was associated with RRC improvement. In summary, HLf could prevent acute ALI in female mice, and RRC likely played an important role.

Summary Objectives Iron amino acid chelates have been developed to be used as food fortificants and therapeutic agents in the treatment of iron deficiency anemia. Purpose To compare the efficacy of Oral iron bisglycinate chelate (FeBC), lactoferrin (LF), lactoferrin with iron and iron polymaltose complex (IPC) in treatment of iron deficiency anemia (IDA). Methods: a comparative study was conducted on 120 children with IDA, they attended to outpatient clinic at Menoufia University Hospitals within a period from April to November 2019. All subjects were classified into FeBC Group (30 children received iron bisglycinate), LF Group (30 children received lactoferrin 100 mg), LF with iron Group (30 children received 30% iron saturated lactoferrin) and IPC Group (30 children received iron polymaltose complex with elemental iron of6 mg/kg/day). Serum iron, serum ferritin, transferrin saturation was investigated. Results After treatment serum iron, serum ferritin and transferrin saturation improved in FeBC group than LF group, in LF with iron group than LF group, and in IPC group than LF group. Serum ferritin improved in LF with iron group than IPC group. Side effects of drugs were higher in FeBC group than LF group, and higher in LF with iron group than FeBC group. Conclusions Adding lactoferrin to iron helps increasing iron stores more than using iron alone in treatment of iron deficiency anemia. Lactoferrin is less effective than lactoferrin with iron, iron bisglycinate chelate and iron polymaltose complex in treatment of iron deficiency anemia.

Lactoferrin (LF), known to be present in mammalian milk, has been reported to promote the proliferation of osteoblasts and suppress bone resorption by affecting osteoclasts. However, the mechanisms underlying the effects of human sources LF on osteoblast differentiation have not yet been elucidated, and almost studies have used LF from bovine sources. The presented study aimed to characterize the molecular mechanisms of bovine lactoferrin (IF-I) and human recombinant lactoferrin (LF-II) on MC3T3-E1 pre-osteoblast cells. MC3T3-E1 cells were treated with LF, ascorbic acid, and β-glycerophosphate (β-GP). Cell proliferation was analyzed using the MTT assay. Alkaline phosphatase activation and osteopontin expression levels were evaluated via cell staining and immunocytochemistry. The differentiation markers were examined using quantitative real-time PCR. The cell viability assay showed the treatment of 100 μg/mL LF significantly increased; however, it was suppressed by the simultaneous treatment of ascorbic acid and β-GP. Alizarin red staining showed that the 100 μg/mL treatment of LF enhanced calcification. Quantitative real-time PCR showed a significant increase in osterix expression. The results suggest that treatment with both LFs enhanced MC3T3-E1 cell differentiation and promoted calcification. The mechanisms of calcification suggest that LFs are affected by an increase in osterix and osteocalcin mRNA levels.

Endometriosis is a disease that is characterized by the ectopic presence of the endometrium or its similar cells. A high prevalence of patients with autoimmune diseases has been reported among patients with endometriosis although the cause of endometriosis remained unknown. Recently, the anti-lactoferrin antibody is reported to be highly detected in autoimmune diseases. This study focused on lactoferrin and anti-lactoferrin antibodies to explore the pathology of endometriosis. Lactoferrin is a substance that regulates inflammation and is produced by neutrophils. Anti-lactoferrin antibody is a type of perinuclear antineutrophil cytoplasmic antibody. The serum lactoferrin and anti-lactoferrin antibody levels were compared among patients with or without endometriosis, revealing significantly higher levels in patients with endometriosis. Additionally, a decreased serum anti-lactoferrin antibody level was observed after surgical endometriosis resection. The receiver operating characteristic curve analysis determined the reference values for the serum lactoferrin and anti-lactoferrin antibody levels. Patients whose serum level exceeded the reference anti-lactoferrin antibody value were significantly higher in more than 40% of cases in the endometriosis group. The rate is comparable to that of autoimmune diseases. This is the first report that anti-lactoferrin antibody is frequently observed in patients with endometriosis, adding a new perspective to the understanding of the pathology of endometriosis although precisely elucidating the mechanism by which lactoferrin and anti-lactoferrin antibody appear in endometriosis in the future is necessary.

Bionutrients (or immunonutrients) are dietary components present in milk, or supplements that could be added to milk diets, that impact health and disease. With few exceptions, most of these are present in human breastmilk and the majority are also present in amniotic fluid. Bionutrients can be proteins and peptides including enzymes, hormones, immunoglobulins, and growth factors and can also be molecules such as human milk oligosaccharides, amino acids, or lipids such as docosahexaenoic acid. Many of these have ancient origins, are found in other species, and existed before mammalian lactation evolved. Bionutrients may act in diverse ways when administered enterally: they may impact gut bacterial communities or epithelial cell metabolism, or they may pass into the lamina propria where they interact with the gut and systemic immune systems. Clinical trials have often used bovine analogs such as lactoferrin or may use artificially synthesized or recombinant compounds including insulin, bile salt stimulated lipase, or oligosaccharides. Challenges arise because the bioactivity of proteins, such as lactoferrin, may be affected by processing and pasteurization meaning that the impacts of commercial products may differ. The challenge of determining the optimal bioactivity of any single preparation may be even greater in complex compounds such as milk fat globule membrane. It is also possible that bioactivity is affected by the milk matrix, that is, may differ between formula and human milk. Finally, it is important to appreciate that nutrients do not function in isolation, and most will not act like drugs, that is, they may take several days or longer to exert an affect.· Breastmilk contains high concentrations of bionutrients and provides more than macro- and micronutrients.. · Bionutrients can be proteins (e.g. enzymes, hormones, or immunoglobulins) or molecules (e.g. human milk oligosaccharides or amino acids).. · Bionutrients can be added to milk feeds but high quality trials are needed..

Aflatoxin M1 (AFM1) is the only mycotoxin with maximum residue limit in milk, which may result in serious human diseases. On the contrary, lactoferrin (Lf) is an active protein with multiple functions. Studies have confirmed that Lf has a powerful potential to protect the intestines, but the influence of Lf on mycotoxins is not clear. This study aims to explore whether Lf can protect the cytotoxicity induced by AFM1, and determine the underlying mechanisms in human normal colonic epithelial NCM460 cells. The results indicated that AFM1 decreased the cell viability, and increased the levels of apoptosis and autophagy of NCM460 cells. Lf can alleviate the cytotoxicity induced by AFM1 through enhancing cell viability, significantly down-regulated the expression of apoptotic genes and proteins (BAX, caspase3, caspase9, caspase3, and caspase9), and regulated the gene and protein expression of autophagy factors (Atg5, Atg7, Atg12, Beclin1, ULK1, ULK2, LC3, and p62). Furthermore, interference of the key gene Atg5 of autophagy can reduce AFM1-induced apoptosis, which is consistent with the role of Lf, implying that Lf may protect AFM1-induced intestinal injury by inhibiting excessive autophagy-mediated apoptosis. Taken together, our data indicated that Lf has a mitigating effect on apoptosis induced by AFM1 through the autophagy pathway.