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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.

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.

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.

Milk lactoferrin is a multi-functional, iron-binding glycoprotein with immunomodulatory effects, protecting infants against infectious diseases.This study explored how maternal inflammation/infection and iron-deficiency anemia (IDA) might influence human milk lactoferrin. Lactoferrin might be elevated with maternal inflammation resulting from infectious disease processes. Conversely, lactoferrin might decrease with IDA, corresponding to scarce maternal iron for transfer in milk. In these two hypothesized scenarios, the degree of lactoferrin elevation or decrease might vary with infant vulnerability to infectious diseases or malnutrition. Alternatively, lactoferrin might be unassociated with inflammation/infection or IDA if mothers could buffer it against these conditions.We used cross-sectional data from Ariaal mothers of northern Kenya (n = 200) to evaluate associations between milk lactoferrin and maternal inflammation/infection, IDA, infant age/sex, and the mother-infant variable interactions in multivariate regression models.Maternal inflammation was associated with higher lactoferrin for younger infants (~5 months of age) but with lower lactoferrin for older infants. Maternal IDA was unassociated with lactoferrin alone or in interaction with infant variables.Results suggest that mothers of vulnerable young infants deliver more lactoferrin when they have inflammation/infection but mothers with older infants do not, and that maternal delivery of lactoferrin is unaffected by their IDA. Longitudinal research should verify these findings.

The analysis of glycoproteins and the comparison of protein N-glycosylation from different eukaryotic origins require unbiased and robust analytical workflows. The structural and functional analysis of vertebrate protein N-glycosylation currently depends extensively on bacterial peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidases (PNGases), which are indispensable enzymatic tools in releasing asparagine-linked oligosaccharides (N-glycans) from glycoproteins. So far, only limited PNGase candidates are available for N-glycans analysis, and particularly the analysis of plant and invertebrate N-glycans is hampered by the lack of suitable PNGases. Furthermore, liquid chromatography-mass spectrometry (LC-MS) workflows, such as hydrogen deuterium exchange mass spectrometry (HDX-MS), require a highly efficient enzymatic release of N-glycans at low pH values to facilitate the comprehensive structural analysis of glycoproteins. Herein, we describe a previously unstudied superacidic bacterial N-glycanase (PNGase H

Objective To investigate the effects of different lactoferrin concentrations on mid-palatal suture bone remodeling during palatal expansion and relapse in rats. Materials and methods Thirty-two 5-week-old male Wistar rats were randomly divided into four groups: EO (expansion only), E+LF1 (expansion plus 10 mg/kg/day daily LF), E+LF2 (expansion plus 100 mg/kg/day daily LF), and E+LF3 (expansion plus 1 g/kg/day daily LF). Thereafter, micro-computed tomography and micro-morphology of the mid-palatal suture were analyzed on day 7 and day 14, respectively. Results The arch widths were increased in all the four groups after expansion, and there was no significant difference among them on day 7. After relapse, however, the arch width in the E+LF3 group was significantly larger compared with EO group. In E+LF3 group and E+LF2 group, new bone formation and osteoblast number were enhanced with up-regulated expression of osteocalcin and collagen type I, while the expression of cathepsin K-positive cells was downregulated in E+LF3 group. Conclusion Lactoferrin gavage administration might increase the stability of palatal expansion and reduce relapse in a concentration-dependent manner by enhancing bone formation and inhibiting resorption. LF administration may be promising for optimizing the maxillary expansion outcome.

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.

As classical MRPs, the toxic effects of furosine, pyralline, and 5‐hydroxymethylfurfural (5‐HMF) in liver tissue are evaluated and the related mechanism is investigated here, and the protective effects of lactoferrin on liver injury caused by Maillard reaction products (MRPs) with furan ring are proved in vitro and in vivo. First, we detect the concentrations of furosine, pyralline, and 5‐HMF in several foods using ultrahigh‐performance liquid chromatography (UHPLC). Then, the effects of the three MRPs on liver cells (HL‐7702) viability, as well as liver tissue, are performed and evaluated. Furthermore, the regulations of three MRPs on necroptosis‐related pathway in liver cells are investigated. Additionally, the effects of lactoferrin in alleviating liver injury, as well as regulating necroptosis pathway, were evaluated. Results elucidate that lactoferrin protects liver injury caused by MRPs with furan ring structure through activating RIPK1/RIPK3/p‐MLKL necroptosis pathway and downstream inflammatory reaction., Lactoferrin protects liver injury caused by MRPs with furan ring structure through activating RIPK1/RIPK3/p‐MLKL necroptosis pathway and downstream inflammatory reaction.

Background Fecal calprotectin (FC) is a non‐invasive marker of gut inflammation which is frequently used to guide therapeutic decisions in patients with inflammatory bowel diseases (IBD). Each step of FC measurement can influence the results, leading to misinterpretations and potentially impacting the management of IBD patients. To date, there is high heterogeneity between FC measurements and no current method is universally accepted as a standard. Aims Our aim was to provide clear position statementsabout the pre‐analytical and the analytical phases of FC measurement to homogenize FC levels and to minimize variability and risk of misinterpretation through aninternational consensus. Materials & Methods Fourteen physicians with expertise in the field of IBD and FC from 11 countries attended a virtual international consensus meeting on July 17th, 2020. A systematic literature was conducted and the literature evidence was shared and discussedamong the participants. Statements were formulated, discussed, and voted. Statements were considered approved if all participants agreed. Results Nine statements were formulated and approved. Based on the available evidence, quantitative tests should be preferred for measuring FC. Furthermore, FC measurement, if possible, should always be performed with the same method and factors influencing FC levels should be taken into account when interpreting the results. Discussion FC has an increasingly important role in the management of patients with IBD. However, large multicenter studies should be conducted to define the reproducibility and to confirm the diagnostic accuracy of the available FC tests. Conclusion FC concentrations guide clinicians' treatment decisions. Our statements have a relevant impact in daily practice and could be applied in clinical trials to standardize FC measurement., Key Summary Summarise the established knowledge on this subject. ‐ FC is a surrogate non‐invasive marker of gut inflammation.‐ FC is closely correlated with endoscopic and histological activity of disease.‐ High variability exists between FC measurements.‐ There is no globally accepted cut‐off of FC. What are the significant findings of this study? ‐ Stool consistency can influence FC extraction.‐ Quantitative tests are recommended for FC measurement.‐ Serial FC measurement in an individual patient should be performed with the same FC test.‐ Interpretation of FC measurement results should include the evaluation of factors that may influence the test.

In this study, five adsorption isotherm models, that is, the Langmuir, Freundlich, Langmuir-Freundlich, Temkin and Brunauer-Emmett-Teller isotherms, were utilized for the analysis of the experimental adsorption data for six classes of poly(N-isopropylacrylamide)-based thermo-responsive copolymer-grafted Sepharose Fast Flow sorbents of different copolymer compositions with two structurally related proteins, namely bovine holo-lactoferrin and bovine holo-transferrin at 20 and 50°C. The experimental data for bovine holo-lactoferrin could be mathematically fitted to the Freundlich and Temkin isotherms when the protein feed concentrations were in the range of 1-40 mg/mL at both 20 and 50°C. Similar analysis of the binding of the homologous protein, bovine holo-transferrin, to the same thermo-responsive copolymer-grafted sorbents revealed that the experimental data could be fitted to the Langmuir, Freundlich and Temkin isotherms with coefficients of determination value over 0.90.

This systematic review aimed at investigating longitudinal changes in human milk bioactive protein concentrations in Chinese population. Both English and Chinese databases were searched. The data were pooled into six defined lactation stages. Weighted means of protein concentrations in each stage and the statistical significance of means of different lactation stages were calculated. The data of 11 bioactive proteins were retrieved. Concentrations of sIgA, IgM, and IgG decreased sharply during the first 14 days of lactation. The levels of α‐lactalbumin, lactoferrin, and β‐casein also decreased throughout lactation. Conversely, lysozyme levels increased over lactation. The changing patterns of the serum albumin, osteopontin, and bile salt‐stimulated lipase (BSSL) were not conclusive. This study represents the most comprehensive summary of bioactive proteins in Chinese human milk. In the future, mass spectrometry‐based analysis of human milk proteomics may be used to investigate the longitudinal changes of many more bioactive proteins., This systematic review aims at investigating the longitudinal changes in the bioactive proteins in the human milk of the Chinese population. The concentrations of α‐lactalbumin, lactoferrin, β‐casein, and three immunoglobulins (sIgA, IgM, and IgG) decrease during lactation. Lysozyme concentrations increase during lactation.

BACKGROUND Genetic variants of β-casein are cosnidered to affect the components of milk. However, limited data are available on the bovine protein components correlated with β-casein variants at the proteome level. In the present study, cows producing milk containing β-casein variants (A1A1 and A2A2) and their heterozygote (A1A2) were identified using a high-resolution melting method, and milk samples were collected and tested. Comparative analyses of casein micelles, whey and milk fat globule membrane fractions in each milk variant were performed using a label-free proteomics approach. RESULTS The results obtained showed that ceruloplasmin and cathelicidin-2 were the most abundant proteins in milk containing variant A1A1; lactoferrin and CD5 molecule-like were the most abundant proteins in milk containing variant A2A2; and selenoprotein P and osteopontin were the most abundant proteins in milk containing heterozygote A1A2. Differences in protein components in milk containing the different β-casein variants were visualized using hierarchical clustering, and profiles were separated using principal components analysis. The differentially expressed proteins in milk containing A1A1, A2A2 or A1A2 were predominantly involved in response to stress and defense response according to their Gene Ontology annotations. CONCLUSION Our findings provide new insights into differentially expressed milk proteins corresponding to the presence of different β-casein variants. This knowledge will help determine their potential biological functions in dairy products and the effects on human health. © 2020 Society of Chemical Industry.

OBJECTIVES The early diagnosis and monitoring of Crohn's disease (CD) and orofacial granulomatosis (OFG) might be facilitated by assaying potential disease biomarkers in saliva. Markers of oxidative stress and inflammation were assayed in salivas from patients with CD, OFG and concurrent OFG and CD (OFG + CD). SUBJECTS Unstimulated whole mouth saliva was collected from 93 subjects, and immunoglobulin A (IgA), lactoferrin (LF) and myeloperoxidase (MPO) were determined by ELISA. Markers of oxidative stress and antioxidant status were assayed spectrophotometrically. RESULTS Immunoglobulin A was significantly (p

Objective: We aim to explain why salivary lactoferrin (Lf) levels are reduced in patients suffering mild cognitive impairment (MCI) and sporadic Alzheimer’s disease (sAD).1 We also will discuss if such Lf decrease could be due to a downregulation of the sAD associated systemic immunity. Background: Several non-neurological alterations have been described in sAD, mainly in skin, blood cell, and immunological capacities. We reviewed briefly the main pathophysiological theories of sAD (amyloid cascade, tau, unfolder protein tau, and amyloid deposits) emphasizing the most brain based hypotheses such as the updated tau-related neuron skeletal hypothesis; we also comment on the systemic theories that emphasize the fetal origin of the complex disorders that include the low inflammatory and immunity theories of sAD. New/updated hypothesis: Lf has important anti-infectious and immunomodulatory roles in health and disease. We present the hypothesis that the reduced levels of saliva Lf could be an effect of immunological disturbances associated to sAD. Under this scenario, two alternative pathways are possible: first, whether sAD could be a systemic disorder (or disorders) related to early immunological and low inflammatory alterations; second, if systemic immunity alterations of sAD manifestations could be downstream of early sAD brain affectations. Major challenges for the hypothesis: The major challenge of the Lf as early sAD biomarker would be its validation in other clinical and population-based studies. It is possible the decreased salivary Lf in early sAD could be related to immunological modulation actions, but other different unknown mechanisms could be the origin of such reduction. Linkage to other major theories:This hypothesis is in agreement with two physiopathological explanations of the sAD as a downstream process determined by the early lesions of the hypothalamus and autonomic vegetative system (neurodegeneration), or as a consequence of low neuroinflammation and dysimmunity since the early life aggravated in the elderly (immunosenescence)

Nitric oxide (NO) is a potentially powerful weapon against Candida albicans, and the regulation of intracellular NO levels is therefore important for controlling its physiological functions. Lactoferricin B like peptide (LBLP) is a 23-mer antimicrobial peptide (AMP) derived from the Scolopendra subspinipes mutilans. We confirmed that LBLP treatment led to the generation of endogenous NO in C. albicans, which was associated with the NO synthase pathway. Here, we examined the antifungal activity of LBLP with focus on intracellular NO. Total glutathione levels were measured to evaluate cellular defense capacity against NO. LBLP decreased total glutathione levels, leading to nitrosative stress. LBLP also inhibited mitochondrial respiration and altered the NAD+/ NADH ratios. Inhibition of mitochondrial respiration induced mitochondrial membrane depolarization, thus leading to calcium homeostasis disruption and mitochondrial superoxide anion accumulation. Consequently, treatment of C. albicans with LBLP resulted in apoptosis. These physiological changes were attenuated when NO generation was inhibited. Our data strongly indicate that LBLP mediates apoptosis by affecting intracellular NO homeostasis. These results on antifungal activity of LBLP and its mechanism indicate the therapeutic promise of this AMP and support the role of NO in cell death regulation.

Background Many foods contain proteins and polyphenols, but there is a poor understanding of the nature of the inhibitory effect of protein on the biologic activity of polyphenols. The inhibitory mechanism of the food protein lactoferrin on the antibacterial activity of oligomeric ellagitannin oenothein B (OeB) was investigated using fluorescence quenching, isothermal titration calorimetry (ITC), circular dichroism (CD) measurement and molecular docking. Results The antibacterial activity of OeB against Staphylococcus aureus was inhibited by lactoferrin, which was retained at about 60%. An interaction study revealed that an interaction occurred between OeB and lactoferrin. Thermodynamic analyses indicate that the binding process was spontaneous, and the main driving forces were based on electrostatic interactions that contributed to a high interaction affinity between OeB and lactoferrin. Furthermore, CD spectra provided insights into conformational changes of lactoferrin. Finally, molecular docking analysis provided a visual representation of a single binding site where OeB interacted with specific amino acid residues located at the active site of lactoferrin. In particular, due to the unique macrocyclic structure and rigid ring structure of OeB, a small number of hydroxyl groups in the rigid structure of OeB interacted with the amino acid of lactoferrin while most of the phenolic hydroxyl groups were not associated with lactoferrin. Conclusion Our study provides a theoretical basis for the use of OeB as an antibacterial substance that can be used in nutraceuticals and pharmaceutical products. © 2020 Society of Chemical Industry.

Background and aims Small intestinal lesions in patients with Behcet disease (BD) have a risk of perforation and hemorrhage requiring surgery. However, no screening strategy for such lesions has been established. We investigated small intestinal lesions in BD patients with video capsule endoscopy (VCE) and analyzed clinical characteristics to identify noninvasive biomarkers of such lesions. Methods This study included 33 BD patients who underwent VCE (PillCam® SB3) at our institution from June 2016 to January 2019. Clinical characteristics, including age, sex, disease duration, body mass index, gastrointestinal symptoms, eye involvement, and blood examinations, were obtained from the medical records of 27 of the 33 patients. Fecal immunochemical tests for hemoglobin, fecal calprotectin (FC), and fecal lactoferrin (FL) were measured. VCE findings of 145 healthy Japanese individuals from a previous report were used as controls. Results Two intestinal BD patients were included in the 27 patients. We observed that BD patients exhibit more small intestinal lesions compared with healthy individuals, including erosions, ulcers, and total lesions (erosions or ulcers). FC and FL levels were significantly higher in patients with versus without small intestinal lesions (P = 0.034 and P = 0.046, respectively). Receiver operating characteristic analyses demonstrated that FC (cutoff value = 119 μg/g) and FL (cutoff value = 17 μg/g) were biomarkers for small intestinal lesions in patients with BD. Conclusion The present study using VCE showed that patients with BD had more small intestinal lesions than healthy individuals. FC and FL could be useful for screening BD patients who may have small intestinal lesions.

Dairy cows feed on isoflavones as physiologically active substances present in legumes. However, the influences of isoflavones (biochanin A, genistein, formononetin, and daidzein) and their metabolites (p-ethylphenol and equol) on milk components production, tight junctions (TJs), and their regulatory pathways are unclear in bovine mammary epithelial cells (BMECs). In this study, we investigated the influences of isoflavones and their metabolites in BMECs using an in vitro culture model. The influences of isoflavones on milk components production, TJ proteins, and STAT5/STAT3 signaling pathways were different in a type-specific manner. Biochanin A decreased the mRNA expression and secretion of both β-casein and lactoferrin while a decrease in activated STAT5 and an increase in activated STAT3. In contrast, equol increased claudin-3, which is the main components for less-permeable TJs in lactation, while an increase in activated STAT5. In addition, a mixture of multiple isoflavones based on the intake of red clover increased secretion of lactoferrin, mRNA expression of β-casein, and amount of claudin-3, but a mixture based on soy did not affect the BMECs. Thus, these results indicate that isoflavones in legumes and the metabolic activity of isoflavones in dairy cows when feeding legumes may affect the milk production ability in BMECs.

In this study, the influence of dietary compounds, including antioxidants (ethylenediaminetetraacid, ascorbic acid, catechin), chitosan and lactoferrin, on the stability of liposomes during in vitro adult and infant digestion was investigated in terms of formation of thiobarbituric acid‐reactive substances (TBARS) and free fatty acid release. Liposomes were more sensitive to degradation in adults than in infants, suggesting lower pH (1.5) and higher concentration of pancreatic enzymes (3.2 mg mL⁻¹) and bile salts (5 mg mL⁻¹) that indicated greater damage to the structure of liposomes. Compared to ethylenediaminetetraacid and ascorbic acid, catechin presented the most apparent protective effect against liposomal oxidation by scavenging free radicals. Chitosan promoted the formation of TBARS, while lactoferrin facilitated the hydrolysis rate of liposomes under both adult and infant conditions. This study provided an insight into the development of healthcare products and functional foods related to liposomes for special populations.

Objective To evaluate the effect of tablets containing lactoferrin (LF) and lactoperoxidase (LPO) on gingival health and oral health-related quality of life in healthy adults. Background Lactoferrin and LPO are host defense factors found in saliva that may contribute to oral health. Materials and methods One hundred and fifty adults were randomly assigned to the administration of high-dose tablets (LF 60 mg/d, LPO 7.8 mg/d), low-dose tablets (LF 20 mg/d, LPO 2.6 mg/d), or placebo tablets for 12 weeks. The gingival index (GI) and plaque index (PlI) were measured at baseline and after 12 weeks. Oral health-related quality of life was assessed by the Oral Health Impact Profile (OHIP) at baseline and at 4, 8, and 12 weeks. Results One hundred and nine healthy subjects were included in the efficacy analysis. In the high-dose group, the GI was significantly reduced after 12 weeks of treatment, and the reduction in GI in the high-dose group was significant compared with the placebo group. In both the high-dose group and the low-dose group, PlI showed a significant decrease at 12 weeks compared with baseline. The total OHIP score was significantly reduced at 12 weeks in the high-dose group. In addition, the OHIP functional limitation subscale displayed significant improvement in the high-dose groups compared with the placebo group at 12 weeks. No adverse reactions or serious adverse events related to the test tablets were observed in any of participants during the study, and the incidence of adverse events unrelated to the tablets did not differ significantly among the groups. Conclusion These results suggest that intake of tablets containing LF (60 mg/d) and LPO (7.8 mg/d) can potentially improve gingival inflammation and oral health-related quality of life in healthy adults.

Pullulan is a polysaccharide polymer commonly used to produce edible films. However, pure pullulan film is usually brittle and very hydrophilic, which limit its use in both food and pharmaceutical fields. The objective of this research is to improve the structural and mechanical properties of pullulan film by incorporating globular protein lactoferrin (LF).The incorporation of LF increased the surface hydrophobicity and decreased the water vapor permeability (WVP) of pullulan film. The presence of low concentrations of LF (0.03%) has no significant influence on tensile strength (TS) and elongation at break (EAB) of pullulan film. However, further increase of LF concentration to levels0.03% resulted in a film-weakening effect. LF molecules aggregated with each other during the film-producing process, which presented as spherical particles from the observation of microscopy. LF aggregates dispersed homogeneously throughout the pullulan matrix and their size increased with increasing concentration. Analysis from Fourier transform infrared spectroscopy indicated that the secondary structure of LF molecules was modified during the drying process.It is possible to increase the hydrophobicity of pullulan film while maintaining its mechanical properties. The produced composite film can be potentially used for food and medical packaging. © 2019 Society of Chemical Industry.

Background Vulvovaginal candidiasis (VVC) is a recurrent vaginal condition in childbearing women. Objectives The aim of this study was to assess the efficacy of an oral formulation containing Lactobacillus acidophilus GLA-14, Lactobacillus rhamnosus HN001 and bovine lactoferrin on symptoms and recurrence of VVC as adjuvant therapy to topical clotrimazole. Patients/methods Forty-eight women positive for C. albicans, symptoms of VVC and documented history of recurrences were randomised into 2 groups receiving verum or placebo (2 capsules/day for 5 days followed by 1 capsule/day for additional 10 days) as adjuvant treatment to clotrimazole (induction phase) followed by a maintenance cycle of 6 months (1 capsule/day verum or placebo for 10 consecutive days each month). Symptoms, overall cure rate and recurrence rate were assessed. Results After clotrimazole therapy, a significant improvement of symptoms was shown in both groups. However, only women treated with probiotics and lactoferrin showed a significant improvement of itching and discharge at 3 and 6 months. During the six-month follow-up, recurrences were significantly less in the intervention group vs placebo (33.3% vs 91.7% after 3 months and 29.2% vs 100% after 6 months). Conclusions The results show that the investigated lactobacilli mixture in combination with lactoferrin represents a safe and effective adjuvant approach for reducing symptoms and recurrences of RVVC.

We report a case of localized bronchial lactoferrin amyloidosis. A 47-year-old man presented with a complaint of persistent dry cough for two months. Chest computed-tomography revealed a calcification shadow of the right main bronchus; hence, a biopsy was performed, showing layered spheroid-type eosinophilic deposits in the bronchial wall. These deposits were positive for Congo red staining, exhibiting apple-green birefringence under polarized light. In addition, an electron microscopic examination demonstrated that this layered structure was formed by very thin cord-like amyloid deposits. By proteomics analysis using liquid chromatography-tandem mass spectrometry and immunohistochemistry, we confirmed that the deposited amyloid was composed of lactoferrin. While lactoferrin is known to be a precursor protein of localized corneal and seminal vesicle amyloidosis, localized lactoferrin amyloidosis of the bronchus has not been reported in the English literature. Our pathological findings suggested that localized lactoferrin amyloidosis may be caused by long-term tissue damage, and the characteristic spheroid-type appearance is thought to be associated with unique, thin cord-like amyloid deposits.

The aim of this study was to explore the genetic polymorphisms in LTF/EcoRI and TLR4/AluI loci and their association with milk and reproductive performance in Holstein cattle. A randomly selected 800 Holstein dairy cows from two dairy farms (400 animals each) in Egypt were used. Based on the two farm records, association between LTF/EcoRI genotypes and milk performance traits (order of lactation, daily milk yield, days in milk, corrected milk at 305 day and dry period) was carried out. Meanwhile, exploring of TLR4/AluI genotypes effect was done on data for reproductive performance (age at first freshening, calving interval, number of services per conception, ovarian rebound and days open). DNA was extracted from blood samples collected from Holstein dairy cows of the both farms and restriction analysis of 301-bp PCR products of LTF gene revealed two genotypes: AA genotype (301 bp) and AB genotype (301, 201 and 100 bp). Meanwhile, restriction analysis of 382-bp PCR products of TLR4 gene digested with AluI yielded two alleles (A and B) and three genotypes (AA, AB and BB). The A allele was indicated by two bands at 300 and 82 bp, and the B allele resulted in three fragments of 160, 140 and 82 bp. There was a significant association (p ≤ 0.05) between LTF genotypes and milk performance traits except for days in milk. The TLR4 genotypes had significant effects (p ≤ 0.05) on age at first freshening, calving interval, number of services per conception, ovarian rebound and days open. Ordinal logistic regression statistical model also revealed that it is possible to calculate high reproductive performance traits and to predict favourable dairy cows based on LTF and TLR4 genotypes. This research reveals the effectiveness of LTF/EcoRI and TLR4/AluI loci as candidates for reproductive performance assessment in Holstein cattle.

Chimeric peptides containing short sequences derived from bovine Lactoferricin (LfcinB) and Buforin II (BFII) were synthetized using solid-phase peptide synthesis (SPPS) and characterized via reversed-phase liquid chromatography and mass spectrometry. The chimeras were obtained with high purity, demonstrating their synthetic viability. The chimeras' antibacterial activity against Gram-positive and Gram-negative strains was evaluated. Our results showed that all the chimeras exhibited greater antibacterial activity against the evaluated strains than the individual sequences, suggesting that chemical binding of short sequences derived from AMPs significantly increased the antibacterial activity. For each strain, the chimera with the best antibacterial activity exerted a bacteriostatic and/or bactericidal effect, which was dependent on the concentration. It was found that: (i) the antibacterial activity of a chimera is mainly influenced by the linked sequences, the palindromic motif RLLRRLLR being the most relevant one; (ii) the inclusion of a spacer between the short sequences did not significantly affect the chimera's synthesis process; however, it enhanced its antibacterial activity against Gram-negative and Gram-positive strains; on the other hand, (iii) the replacement of Arg with Lys in the LfcinB or BFII sequences improved the chimeras' synthesis process without significantly affecting their antibacterial activity. These results illustrate the great importance of the synthesis of chimeric peptides for the generation of promising antibacterial peptides.

The purpose of this study was to investigate effects of addition of lactoferrin on characteristics and functions of bovine epididymal, ejaculated, and frozen-thawed sperm. The addition of lactoferrin was significantly (p < .05) effective on increasing values of progressive motility, straightness, and linearity in caput epididymal sperm and values of motility in cauda epididymal sperm. When ejaculated sperm were incubated in capacitation medium, percentages of motile and progressively motile sperm decreased largely within the first period of 30 min, followed by only minor changes. However, the addition of lactoferrin significantly lessened the early decreases of these parameters and additionally promoted capacitation-dependent changes of chlortetracycline staining patterns (from F pattern to B pattern). In other experiments, when ejaculated sperm were exposed to oxidative stress with 100-µM H2 O2 , the addition of lactoferrin partially protected them from dysfunction of flagellar movement and loss of progressive movement. In final experiments with frozen-thawed samples incubated in the capacitation medium, the addition of lactoferrin effectively survived dying sperm and suppressed occurrence of sperm agglutination. These results may suggest biological and biotechnological potentials of lactoferrin for modulation of bovine sperm viability, motility, capacitation state, and preservation in vitro.

Two conundrums puzzle COVID-19 investigators: 1) morbidity and mortality is rare among infants and young children and 2) rates of morbidity and mortality exhibit large variances across nations, locales, and even within cities. It is found that the higher the rate of pneumococcal vaccination in a nation (or city) the lower the COVID-19 morbidity and mortality. Vaccination rates with Bacillus Calmette-Guerin, poliovirus, and other vaccines do not correlate with COVID-19 risks, nor do COVID-19 case or death rates correlate with number of people in the population with diabetes, obesity, or adults over 65. Infant protection may be due to maternal antibodies and antiviral proteins in milk such as lactoferrin that are known to protect against coronavirus infections. Subsequent protection might then be conferred (and correlate with) rates of Haemophilus influenzae type B (Hib) (universal in infants) and pneumococcal vaccination, the latter varying widely by geography among infants, at-risk adults, and the elderly. Also see the video abstract here https://youtu.be/GODBYRbPL00.

Antibacterial factors act as innate immune components, which respond as soon as bacteria enter a living organism. To prevent and treat mastitis in cattle, understanding the concentrations of these substances inside the udder is important; however, they remain to be studied. In this investigation, the concentration of lingual antimicrobial peptide (LAP), S100 protein (S100A7), lactoferrin (LF), and immunoglobulin antibody were measured in the different fractions of foremilk. Lactating Holstein cows were examined, and 10 foremilk fractions were obtained from sequential samples up to 150 ml. The LAP concentrations in milk samples increased until 25 ml. The LF concentrations increased up to the 10 ml fraction, then stabilized at low level after the 50 ml fraction. For S100A7, some fractions had significantly higher (p

The incidence of bovine mastitis and the bulk milk somatic cell count (BMSCC) are influenced by season, which may be associated with innate immune functions, including antimicrobial components in mammary glands. Therefore, the present study was conducted to examine the effect of season on antimicrobial components in milk. Rectal temperature and plasma cortisol, thyroxine, and derivatives of reactive oxygen metabolites (d-ROMs) were measured as stress parameters. Concentrations of lactoferrin (LF), lingual antimicrobial peptide (LAP), psoriasin (S100A7), and Immunoglobulin A (IgA) in milk were measured as indicators of innate immune function. LF and LAP concentrations were significantly lower in summer than in winter and spring, respectively, whereas the concentration of S100A7 was significantly lower in winter than in spring and autumn. The rectal temperature was significantly higher in summer than in other seasons, whereas plasma cortisol, thyroxine, and d-ROMs did not exhibit any seasonal variation. In conclusion, even though stress parameters were not changed, the concentration of antimicrobial components, such as LF and LAP, decreased in summer, which may explain the frequent occurrence of mastitis during this season.

OBJECTIVE Dental caries is related to cariogenic bacteria, salivary components, oral hygiene and host susceptibility. Lactoferrin is an important antimicrobial glycoprotein in saliva; however, the role of the LTF gene in caries susceptibility is unclear. We investigated the association between LTF polymorphisms and the severity of caries. DESIGN Our study included 910 healthy paediatric subjects (aged 24-48 months) categorised into three groups: 403 with no caries or white-spot lesions; 230 with moderate caries (8 ≤ dmft ≤ 12); and 277 with severe caries (13 ≤ dmft ≤ 20). Information regarding the subjects' oral habits was gathered using questionnaires. The LTF rs1126477 and rs1126478 polymorphism alleles were genotyped by Sanger sequencing. RESULTS The three groups showed no significant differences in LTF polymorphisms alleles, genotypes or haplotypes distribution. Multifactor dimensionality reduction analysis showed that the interactions between breastfeeding for a duration >24 months, night feeding >24 months and high frequency of sweet food intake increased the risk of caries (p = 0.0014); however, we detected no interaction effect between the LTF polymorphisms and oral habits on caries susceptibility. CONCLUSIONS The LTF rs1126477 and rs1126478 polymorphisms showed no association with the different levels of caries risk in our Chinese paediatric cohort.

Background: The current study aimed to prepare antimicrobial agents for food preservation from crude cheese whey. Crude cheese whey was digested with porcine pepsin, and calf and fungal rennets at various pHs. The digests were assessed for antibacterial activities against Escherichia coli and Bacillus subtilis.; Results: The calf rennet digest at pH 3.0 showed the highest antibacterial activity. Three antibacterial peptides that acted against B. subtilis lactoferrin f(20-30), and β-lactoglobulin f(14-22) and f(92-103) were identified in the calf rennet digest. Only lactoferrin f(20-30) also exerted bactericidal activity against E. coli. LC-MS/MS analysis revealed that the three peptides were generated by the porcine pepsin at pH 2.5, whereas the calf rennet generated them at a wider pH (pH 2.5-3.5). Fungal rennet generated only β-lactoglobulin f14-22 at pH 3.5. The pepsin and calf rennet digests at pH 2.5 and 3.0, respectively, reduced the E. coli and B. subtilis populations by approximately 2 log at 6000 µg mL-1 in milk at 4 °C.; Conclusion: The calf rennet and porcine pepsin digests of cheese whey, at a specific acidic pH, which can be prepared from food-grade materials, have the potential to be used as natural food preservatives due to the presence of the three antibacterial peptides. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

Lactoferrin (LF) was previously suggested to have a protective effect against liver fibrosis by preventing hepatic stellate cells (HSCs) activation. The effect of LF on heat shock protein 47 (HSP47) has not yet been studied so this study was designed to investigate LF effect on HSP47 as a potential target for management of liver fibrosis and comparing it with silymarin (SM) in a thioacetamide (TAA)-induced liver fibrosis model. Rats were divided into four groups; normal control, TAA (TAA-treated), LF (LF + TAA-treated), and SM (SM + TAA-treated). After 6 weeks, both LF and SM improved the grade of cirrhosis, reduced collagen fibers deposition, inactivated HSCs, significantly decreased elevated liver enzymes, HSP47, hydroxyproline content, transforming growth factor-beta 1, matrix metalloproteinase-2, 8-hydroxydeoxyguanosine, malondialdehyde, nitric oxide levels and the percentage of alpha smooth muscle actin positive HSCs compared with TAA group. Moreover, LF significantly increased the total antioxidant capacity compared with TAA group. It could be concluded that LF is a promising antifibrotic drug and could be considered as one of the HSP47 inhibitors but SM is still more potent. © 2018 IUBMB Life, 70(8):795-805, 2018.

Mesenchymal stem cells (MSCs) have been investigated to treat liver diseases, but the efficiency of MSCs to treat chronic liver diseases is conflicting. FGF21 can reduce inflammation and fibrosis. We established FGF21‐secreting adipose derived stem cells (FGF21_ADSCs) to enhance the effects of ADSCs and transplanted them into thioacetamide (TAA)‐induced liver fibrosis mice via the tail vein. Transplantation of FGF21_ADSCs significantly improved liver fibrosis by decreasing serum hyaluronic acid and reducing the expression of fibrosis‐related factors such as α‐smooth muscle actin (α‐SMA), collagen and tissue inhibitor of metalloproteinase‐1 (TIMP‐1) compared with the Empty_ADSCs by inhibition of p‐JNK, NF‐κB and p‐Smad2/3 signalling. α‐lactoalbumin (LA) and lactotransferrin (LTF), secretory factors produced from FGF21_ADSCs inhibited TGF‐β1‐induced expression of α‐SMA and collagen in LX‐2 cells. These results suggest that transplantation of FGF21_ADSCs inhibited liver fibrosis more effectively than Empty_ADSCs, possibly via secretion of α‐LA and LTF.

Background and objective The response to nonsurgical periodontal treatment varied among patients. This study assessed the potential of salivary biomarkers for predicting the sensitivity and monitoring the response to nonsurgical periodontal therapy. Material and methods This study recruited 34 participants with severe chronic periodontitis (the test group) and 20 participants without periodontal destruction in any teeth (the control group) from September 6, 2013 to August 25, 2017. Participants in the test group received nonsurgical periodontal therapy and were further divided into 2 subgroups of 17 low responders and 17 high responders, based on probing depth reduction. Clinical periodontal parameters were recorded, and saliva samples were harvested before and after nonsurgical periodontal therapy. Salivary biomarkers, including interleukin (IL)-1beta (IL-1β), IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, platelet-derived growth factor-BB, vascular endothelial growth factor, MMP-8, MMP-9, C-reactive protein, and lactoferrin were analyzed. Results Compared with participants in the control group, participants in the test group had significantly greater periodontal pocket depth, clinical attachment level, and salivary IL-1β and MMP-8 levels, and all of these parameters were significantly reduced after nonsurgical periodontal therapy. The pretreatment levels of IL-1β, MMP-8, and lactoferrin were significantly higher in participants of the high-responder subgroup than participants of the low-responder subgroup.Based on the analysis from a dichotomous table, MMP-8 and lactoferrin showed odds ratios of 5.76, with 71% sensitivity and 71% specificity, and statistical significance (P = .02) for discriminating between the high- and low-responder subgroups. Conclusion Salivary IL-1β and MMP-8 might be useful for diagnosing periodontitis and monitoring the recovery of periodontitis following nonsurgical periodontal therapy. MMP-8 and lactoferrin showed potential for predicting the sensitivity to the treatment.