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Stable ternary complexes of lactoferrin (LF), high methoxyl pectin (HMP) and chlorogenic acid (CGA) were synthesised and characterised. Soluble LF–HMP complexes were prepared at pH 5, 6 and 7 using established phase diagram. CGA bound to ternary complexes at moderate binding strength (Ka: 103–105 L/M). LF, HMP and CGA interacted via noncovalent interactions like hydrophobic interaction. Ternary complexes showed particle size of 135–462 nm (except for 0.05% CGA at pH 5) and zeta‐potential from −17 to −22 mV. Ternary complexes had superior antioxidant capacity over binary ones (P < 0.05). The ternary complexes may find application in functional beverages. [ABSTRACT FROM AUTHOR]

Genetic improvement of udder health in dairy cows is of high relevance as mastitis is one of the most prevalent diseases. Since it is known that the heritability of mastitis is low and direct data on mastitis cases are often not available in large numbers, auxiliary traits, such as somatic cell count (SCC) are used for the genetic evaluation of udder health. In previous studies, models to predict clinical mastitis based on mid‐infrared (MIR) spectral data and a somatic cell count‐derived score (SCS) were developed. Those models can provide a probability of mastitis for each cow at every test‐day, which is potentially useful as an additional auxiliary trait for the genetic evaluation of udder health. Furthermore, MIR spectral data were used to estimate contents of lactoferrin, a glycoprotein positively associated with immune response. The present study aimed to estimate heritabilities (h2) and genetic correlations (ra) for clinical mastitis diagnosis (CM), SCS, MIR‐predicted mastitis probability (MIRprob), MIR + SCS‐predicted mastitis probability (MIRSCSprob) and lactoferrin estimates (LF). Data for this study were collected within the routine milk recording and health monitoring system of Austria from 2014 to 2021 and included records of approximately 54,000 Fleckvieh cows. Analyses were performed in two datasets, including test‐day records from 5 to 150 or 5 to 305 days in milk. Prediction models were applied to obtain MIR‐ and SCS‐based phenotypes (MIRprob, MIRSCSprob, LF). To estimate heritabilities and genetic correlations bivariate linear animal models were applied for all traits. A lactation model was used for CM, defined as a binary trait, and a test‐day model for all other continuous traits. In addition to the random animal genetic effect, the fixed effects year‐season of calving and parity‐age at calving and the random permanent environmental effect were considered in all models. For CM the random herd‐year effect, for continuous traits the random herd‐test day effect and the covariate days in milk (linear and quadratic) were additionally fitted. The obtained genetic parameters were similar in both datasets. The heritability found for CM was expectedly low (h2 = 0.02). For SCS and MIRSCSprob, heritability estimates ranged from 0.23 to 0.25, and for MIRprob and LF from 0.15 to 0.17. CM was highly correlated with SCS and MIRSCSprob (ra = 0.85 to 0.88). Genetic correlations of CM were moderate with MIRprob (ra = 0.26 and 0.37) during 150 and 305 days in milk, respectively and low with LF (h2 = 0.10 and 0.11). However, basic selection index calculations indicate that the added value of the new MIR‐predicted phenotypes is limited for genetic evaluation of udder health. [ABSTRACT FROM AUTHOR]

Glyceraldehyde‐3‐phosphate‐dehydrogenase (GAPDH; EC1.2.1.12) has several functions in Mycobacterium tuberculosis (Mtb) and the human host. Apart from its role in glycolysis, it serves both as a cell surface and a secreted receptor for plasmin(ogen) (Plg/Plm), transferrin (Tf), and lactoferrin (Lf). Plg sequestration by Mtb GAPDH facilitates bacterial adhesion and tissue invasion, while an equivalent interaction with host GAPDH regulates immune cell migration. In both, host and microbe, internalization of Tf/Lf‐GAPDH complexes serves as a route for iron acquisition. To date, the structure of Mtb GAPDH or the residues involved in these moonlighting interactions have not been identified. This study provides the first known X‐ray crystal structure of Mtb GAPDH. Through further mutagenesis and functional assays, we found that the C‐terminal lysines of Mtb and human GAPDH affect enzyme activity and ligand binding. We also establish the stoichiometry of Plg, Tf and Lf interactions with the GAPDH tetramer. Lastly, molecular simulation studies reveal the interactions of the C‐terminal lysine residues. [ABSTRACT FROM AUTHOR]

Summary: Background: In coeliac disease and environmental enteropathy, dietary gluten and enteric infections cause reversible inflammation and morphological changes to the small intestinal mucosa that can be detected in biopsy samples obtained by endoscopy. However, there is a clear need for non‐invasive biomarkers. Constant shedding of mucosal material into the bowel lumen and faeces, together with easy availability of stool, makes it an interesting sample matrix. Aims: To conduct a systematic literature search and summarize the existing evidence for host mucosa‐derived faecal biomarkers in evaluating small intestinal damage. Methods: We searched for studies on PubMed (MEDLINE) until 1 March 2024. Results: We identified 494 studies and included 35 original case–control and cohort studies. These assessed host mucosal transcripts and 14 other markers aiming specifically to reflect inflammation and cell‐mediated, innate and gluten‐induced immune responses. In coeliac disease, faecal calprotectin and anti‐gliadin, tissue transglutaminase, endomysium and deamidated gliadin peptide antibodies were the most studied but with inconsistent results. Single studies reported positive findings about microRNA transcripts, β‐defensin‐2, lipocalin‐2, zonulin‐related proteins and angiotensin‐converting enzyme. In environmental enteropathy, a non‐significant association was reported between calprotectin and urine lactulose/mannitol ratio; there were conflicting results for neopterin, myeloperoxidase and host transcripts. Single studies reported a positive association for lactoferrin, and a negative association for regenerating islet‐derived protein 1. Studies comparing faecal markers against small intestinal biopsy findings were not identified in environmental enteropathy. Conclusions: Further studies are needed to determine reliable faecal markers as a proxy for small intestinal mucosal damage. [ABSTRACT FROM AUTHOR]

Aim: To examine how reduced iron content and added bovine lactoferrin in infant formula affect the antibody response following routine immunisation. Methods: In this randomised controlled trial, 180 Swedish formula‐fed infants received, from 6 weeks to 6 months of age, a 2 mg/L iron formula with (n = 72) or without (n = 72) bovine lactoferrin, or a control formula with 8 mg/L iron and no lactoferrin (n = 36). Another 72 infants were recruited as a breastfed reference. Serum immunoglobulin G (IgG) levels against Haemophilus influenzae type b (Hib), diphtheria and tetanus were assessed at four, six and 12 months of age. Results: With an equal gender distribution, 180 + 72 term infants were included with a mean age of 7.0 ± 0.7 weeks. At 12 months, infants fed low iron formula showed a significantly higher geometric mean Hib IgG (1.40 μg/mL [1.07–1.83]) compared to the control formula infants (0.67 μg/mL [0.42–1.07]). For all three vaccines, breastfed infants had significantly lower IgG levels at six and 12 months of age. Conclusion: Except for higher Hib IgG levels at 12 months in infants fed low iron formula, the interventions did not affect vaccine IgG response. Unexpectedly, breastfed infants had significantly lower vaccine IgG levels compared to formula‐fed infants. [ABSTRACT FROM AUTHOR]

Lactoferrin and polyphenols are common natural functional compounds. Their interactions and the consequential alterations in functional activity have received widespread attention. The work aimed to investigate the interaction between lactoferrin and kaempferol, as well as evaluate the in vitro anticancer properties of the lactoferrin–kaempferol complex. The results of the spectra experiments revealed that lactoferrin and kaempferol are capable of forming complexes to quench the endogenous fluorescence of lactoferrin. Further insight into the binding mechanism was gained through molecular docking and molecular dynamics simulations. These analyses suggest that both hydrophobic interactions and hydrogen bonding are essential factors in the interaction between lactoferrin and kaempferol. Furthermore, the MTT assay and apoptosis by flow cytometry were conducted, revealing a synergistic effect of kaempferol and lactoferrin on the inhibition of HeLa cell proliferation. The findings from this investigation could improve our understanding of lactoferrin's interaction with polyphenols and the role of the lactoferrin–kaempferol complex in inhibiting cancer cell proliferation. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Curcumin is widely known for its antioxidant and anti‐inflammatory properties, but its mechanism of action in mitigating oxidative stress injury in brain vascular endothelial cells remains unclear. Due to the poor bioavailability of curcumin, it is challenging to achieve effective concentrations at the target sites. Nano‐micelles are known for their ability to improve the solubility, stability, and bioavailability of hydrophobic compounds like curcumin. This study investigated the effects and mechanisms of free curcumin and curcumin embedded in nano‐micelles (M(Cur)) on oxidative stress‐induced injury in bEnd.3 cells.At a protective concentration of 10 μg mL−1, micellar curcumin was better able to recover the morphology of bEnd.3 cells under oxidative stress while increasing cell viability, restoring mitochondrial membrane electrical potential, and effectively inhibiting reactive oxygen species generation with a positive cell rate of 2.21%. These results indicate that curcumin significantly improves H2O2‐induced oxidative stress damage in endothelial cells by maintaining the cellular antioxidant balance.This study adds to knowledge regarding the role of nano‐micelles in curcumin intervention for endothelial cell oxidative damage and provides insights for the development of curcumin‐based dietary supplements. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Hydrogels with cell adhesive moieties stand out as promising materials to enhance tissue healing and regeneration. Nonetheless, bacterial infections of the implants represent an unmet major concern. In the present work, we developed an alginate hydrogel modified with a multifunctional peptide containing the RGD cell adhesive motif in combination with an antibacterial peptide derived from the 1–11 region of lactoferrin (LF). The RGD‐LF branched peptide was successfully anchored to the alginate backbone by carbodiimide chemistry, as demonstrated by 1H NMR and fluorescence measurements. The functionalized hydrogel presented desirable physicochemical properties (porosity, swelling and rheological behavior) to develop biomaterials for tissue engineering. The viability of mesenchymal stem cells (MSCs) on the peptide‐functionalized hydrogels was excellent, with values higher than 85 % at day 1, and higher than 95 % after 14 days in culture. Moreover, the biological characterization demonstrated the ability of the hydrogels to significantly enhance ALP activity of MSCs as well as to decrease bacterial colonization of both Gram‐positive and Gram‐negative models. Such results prove the potential of the functionalized hydrogels as novel biomaterials for tissue engineering, simultaneously displaying cell adhesive activity and the capacity to prevent bacterial contamination, a dual bioactivity commonly not found for these types of hydrogels. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Anthocyanins are susceptible to degradation due to external factors. Despite the potential for improved anthocyanin stability with whey protein isolate (WPI), the specific effects of individual components within WPI on the stability of anthocyanins have yet to be studied extensively. This study investigated the interaction of WPI, β‐lactoglobulin (β‐Lg), bovine serum albumin (BSA), and lactoferrin (LF) with cyanidin‐3‐O‐glucoside (C3G), and also considered their effects on stability.Fluorescence analysis revealed static quenching effects between C3G and WPI, β‐Lg, BSA, and LF. The binding constants were 1.923 × 103 L · mol⁻¹ for WPI, 24.55 × 103 L · mol⁻¹ for β‐Lg, 57.25 × 103 L · mol⁻¹ for BSA, and 1.280 × 103 L · mol⁻¹ for LF. Hydrogen bonds, van der Waals forces, and electrostatic attraction were the predominant forces in the interactions between C3G and WPI and between C3G and BSA. Hydrophobic interaction was the main binding force in the interaction between C3G and β‐Lg and between C3G and LF. The binding of C3G with WPI, β‐Lg, BSA, and LF was driven by different thermodynamic parameters. Enthalpy changes (∆H) were −38.76 kJ · mol⁻¹ for WPI, −17.59 kJ · mol⁻¹ for β‐Lg, −16.09 kJ · mol⁻¹ for BSA, and 39.50 kJ · mol⁻¹ for LF. Entropy changes (∆S) were −67.21 J · mol⁻¹·K⁻¹ for WPI, 3.72 J · mol⁻¹·K⁻¹ for β‐Lg, 37.09 J · mol⁻¹·K⁻¹ for BSA, and 192.04 J · mol⁻¹·K⁻¹ for LF. The addition of C3G influenced the secondary structure of the proteins. The decrease in the α‐helix content suggested a disruption and loosening of the hydrogen bond network structure. The presence of proteins enhanced the light stability and thermal stability (stability in the presence of light and heat) of C3G. In vitro simulated digestion experiments demonstrated that the addition of proteins led to a delayed degradation of C3G and to improved antioxidant capacity.The presence of WPI and its components enhanced the thermal stability, light stability, and oxidation stability of C3G. Preheated proteins exhibited a more pronounced effect than unheated proteins. These findings highlight the potential of preheating protein at appropriate temperatures to preserve C3G stability and bioactivity during food processing. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

To develop novel bovine lactoferrin (bLF) peptides targeting bLF‐tumour necrosis factor (TNF) receptor‐associated factor 6 (TRAF6) binding sites, we identified two peptides that could target bLF‐TRAF6 binding sites using structural analysis. Moreover, another peptide that could bind to the TRAF6 dimerization area was selected from the bLF sequence. The effects of each peptide on cytokine expression in lipopolysaccharide (LPS)‐stimulated osteoblasts (ST2) and on osteoclastogenesis were examined using an LPS‐treated co‐culture of primary bone marrow cells (BMCs) with ST2 cells and a single culture of osteoclast precursor cells (RAW‐D) treated with soluble receptor activator of NF‐κB ligand. Finally, the effectiveness of these peptides against LPS‐induced alveolar bone destruction was assessed. Two of the three peptides significantly suppressed LPS‐induced TNF‐α and interleukin‐1β expression in ST2 cells. Additionally, these peptides inhibited and reversed LPS‐induced receptor activator of NF‐κB ligand (RANKL) upregulation and osteoprotegerin (OPG) downregulation, respectively. Furthermore, both peptides significantly reduced LPS‐induced osteoclastogenesis in the BMC‐ST2 co‐culture and RANKL‐induced osteoclastogenesis in RAW‐D cells. In vivo, topical application of these peptides significantly reduced the osteoclast number by downregulating RANKL and upregulating OPG in the periodontal ligament. It is indicated that the novel bLF peptides can be used to treat periodontitis‐associated bone destruction. [ABSTRACT FROM AUTHOR]

Background and Aim: Recently, noninvasive fecal markers have been used as indicators of intestinal inflammation in patients with inflammatory bowel disease (IBD). We conducted a clinical validation study to measure fecal calprotectin (Cp), lactoferrin (Lf), and hemoglobin (Hb) levels using an all‐in‐one kit in patients with IBD and colorectal tumors and aimed to clarify the utility of these fecal markers. Methods: In this study, 104 patients were analyzed, including 25 patients with ulcerative colitis (UC), 20 with Crohn's disease (CD), 48 with colorectal tumors, and 13 healthy controls (HC). Of the 48 patients with colorectal tumors, 14 had invasive cancer. We validated the utility of fecal Cp, Lf, and Hb levels by simultaneously measuring fecal markers in patients with IBD and colorectal tumors. Results: Fecal Cp and Lf had almost equivalent abilities in detecting clinical remission in patients with UC; however, fecal Cp was slightly superior to Lf. Regarding colorectal tumors, fecal Cp and Lf levels tended to be higher in patients with adenomas and colorectal cancer than in HCs. Although fecal Hb alone had the best sensitivity and specificity for detecting colorectal cancer, it had relatively low sensitivity for detecting advanced neoplasms and colorectal cancer. Conclusion: Fecal Cp and Lf can be used as almost equivalent biomarkers to assess the clinical activity in patients with UC. Fecal Hb is the most useful marker for screening colorectal cancer; however, adding fecal Cp and Lf may compensate for the low sensitivity of detecting for advanced colorectal tumors based on Hb alone. [ABSTRACT FROM AUTHOR]

The major functional properties of lactoferrin (LF) samples before and after high‐temperature short‐time (HTST: 72°C/15 s, 85°C/15 s and 95°C/15 s) treatment were investigated by turbiscan stability index, circular dichroism spectroscopy and other methods. The lower the LF iron saturation, the higher the iron binding, antibacterial and antioxidant capacity, but more unstable after HTST treatment. 40%‐LF had the best physical and structural stability, but lower antibacterial and antioxidant capacity. Upon HTST treatment, the physical stability, antibacterial and antioxidant properties of LF samples were significantly reduced, especially for 95°C/15 s. Of note, LF with iron saturation higher than 15% was resistant to HTST treatment. [ABSTRACT FROM AUTHOR]

Bovine lactoferrin (bLF) is a glycosylated protein with purported beneficial properties. The aim of this work was to determine the role of bLF glycosylation in the adhesion, internalization, and growth inhibition of cancer cells. The viability of cervix (HeLa) and colon (Caco‐2) cancer cells (MTT assay and epifluorescence microscopy) was inhibited by bLF, while deglycosylated bLF (bLFdeg) had no effect. Adhesion to cell surfaces was quantified by immunofluorescence assay and showed that bLF was able to bind more efficiently to both cell lines than bLFdeg. Microscopic observations indicated that bLF glycosylation favored bLF binding to epithelial cells and that it was endocytosed through caveolin‐1‐mediated internalization. In addition, the mechanism of action of bLF on cancer cell proliferation was investigated by determining the amount of phosphorylated intermediates of signaling pathways such as epidermal growth factor receptor (EGFR), extracellular signal‐regulated kinase (ERK) and protein kinase B (known as Akt). Chemoluminescence immunoassay of phosphorylated intermediates showed that bLF inhibited Akt phosphorylation, consistent with its growth inhibiting activity. This assay also indicated that the bLF receptor/signaling pathways may be different in the two cell lines, Caco‐2 and HeLa. This work confirmed the effect of glycosylated bLF in inhibiting cancer cell growth and that glycosylation is required for optimal surface adhesion, internalization, and inhibition of the ERK/Akt pathway of cell proliferation through glycosylated cell surface receptors. [ABSTRACT FROM AUTHOR]

The current study presents the first spectrofluorimetric approach for the estimation of lactoferrin, depending on the measurement of its native fluorescence at 337 nm after excitation at 230 nm, without the need for any hazardous chemicals or reagents. It was found that the fluorescence intensity versus concentration calibration plot was linear over the concentration range of 0.1–10.0 μg/mL with quantitation and detection limits of 0.082 and 0.027 μg/mL, respectively. The method was accordingly validated according to the ICH recommendations. The developed method was applied for the estimation of lactoferrin in different dosage forms, including capsules and sachets with high percent recoveries (97.84–102.53) and low %RSD values (<1.95). Lactoferrin is one of the key nutrients in milk powder and a significant nutritional fortifier. In order to assess the quality of milk powder, it is essential to rapidly and accurately quantify the lactoferrin content of the product. Therefore, the presented study was successfully applied for the selective estimation of lactoferrin in milk powder with acceptable percent recoveries (96.45–104.92) and %RSD values (≤3.607). Finally, the green profile of the method was estimated using two assessment tools: Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE), which demonstrated its excellent greenness. [ABSTRACT FROM AUTHOR]

Background and Purpose: Overexpression of astrocytic lactoferrin (Lf) was observed in the brain of Alzheimer's disease (AD) patients, whereas the role of astrocytic Lf in AD progression remains unexplored. In this study, we aimed to evaluate the effects of astrocytic Lf on AD progression. Experimental Approach: Male APP/PS1 mice with astrocytes overexpressing human Lf were developed to evaluate the effects of astrocytic Lf on AD progression. N2a‐sw cells also were employed to further uncover the mechanism of astrocytic Lf on β‐amyloid (Aβ) production. Key Results: Astrocytic Lf overexpression increased protein phosphatase 2A (PP2A) activity and reduced amyloid precursor protein (APP) phosphorylation, Aβ burden and tau hyperphosphorylation in APP/PS1 mice. Mechanistically, astrocytic Lf overexpression promoted the uptake of astrocytic Lf into neurons in APP/PS1 mice, and conditional medium from astrocytes overexpressing Lf inhibited p‐APP (Thr668) expression in N2a‐sw cells. Furthermore, recombinant human Lf (hLf) significantly enhanced PP2A activity and inhibited p‐APP expression, whereas inhibition of p38 or PP2A activities abrogated the hLf‐induced p‐APP down‐regulation in N2a‐sw cells. Additionally, hLf promoted the interaction of p38 and PP2A via p38 activation, thereby enhancing PP2A activity, and low‐density lipoprotein receptor‐related protein 1 (LRP1) knockdown significantly reversed the hLf‐induced p38 activation and p‐APP down‐regulation. Conclusions and Implications: Our data suggested that astrocytic Lf promoted neuronal p38 activation, via targeting to LRP1, subsequently promoting p38 binding to PP2A to enhance PP2A enzyme activity, which finally inhibited Aβ production via APP dephosphorylation. In conclusion, promoting astrocytic Lf expression may be a potential strategy against AD. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc [ABSTRACT FROM AUTHOR]

The effects of in ovo lactoferrin (Lf) injection on some physiological parameters and immune response of posthatch chicks were investigated. Live embryonated Fayoumi chicken eggs (n = 600) were randomly allocated into four groups. The first group as a control was noninjected eggs, the second group was only injected with 0.1 mL of NaCl 0.75% solution, and the third and fourth groups were injected with 50 and 100 µL Lf dissolved in 0.1 mL saline solution respectively. The eggs were injected on Day 15 of incubation in the amnion. The results illustrated that the hatchability of eggs in two Lf groups was significantly higher than in the control, NaCl groups. The residual yolk in chicks injected with Lf (100 µL/egg) was significantly lower than the control group (p < 0.05). In ovo Lf injection improved lipid profile, liver function, antioxidant indices, blood haematology, serum immunoglobulins and jejunum histomorphometry compared to the control group (p < 0.05). In ovo injection of Lf decreased significantly (p < 0.001) of pathogenic bacteria in residual yolk such as Salmonella, Shigella and Coliform compared to the control group. In conclusion, in ovo Lf injection can improve the hatchability, lipid profile, immune response and antioxidant indices and decline pathogens in the residual yolk, thus boosting the health status of newly hatched Fayoumi chicks. [ABSTRACT FROM AUTHOR]

Background: This study follows an initial scientific validation linking sodium ascorbate (SAC) with elastin conservation and the clinical trial histology observation that the full formulation tested there stimulated elastin development. In an effort to explain the increased elastin response, a candidate was sought that may provide synergy to SAC during elastin stimulation. Lactoferrin was the constituent chosen to explore in this realm. Materials and Methods: Using the previously described ex vivo skin model, freshly collected discarded human skin from 2 donors was used to evaluate the effects of lactoferrin and SAC alone and together, and L‐ascorbate CE Ferulic formulation (CEF) on elastogenesis. Four skin explants were topically subjected to the treatments daily for 7 days and one group was left untreated as a negative control. The tissue was fixed and embedded. Sections were evaluated by immunofluorescence using antibodies targeting Tropoelastin and CD44, with DAPI counterstaining to observe nuclei. Images were then analyzed using ImageJ. Results: Treatment with SAC and lactoferrin demonstrated a significant synergistic effect on tropoelastin stimulation compared to the single treatments. In addition, this combination demonstrated intact and increased elastin fibers in contrast to the CEF, which portrayed fragmented elastin fibers. In addition, an additive effect of SAC also contributed to the enhanced CD44, suggesting an increased presence of hyaluronic acid, a new observation for this compound. Conclusion: This study complements a series of studies that have been undertaken to validate the efficacy of a novel antioxidant formulation. Aside from its efficacy in ROS management, the SAC constituent is unique in the different forms of Vitamin C for its ability to conserve elastin. Prior clinical studies demonstrated additive elastin stimulation on histology, not just conservation. From this current study, the combination of SAC with lactoferrin may be responsible for this additive stimulatory effect on elastin. This presents a significant advance in topical antioxidant formulations where the Vitamin C component provides antioxidant and collagen stimulation with additional elastin stimulation rather than degradation. [ABSTRACT FROM AUTHOR]

Several cellular processes, including the recovery of misfolded proteins, the folding of polypeptide chains, transit of polypeptides across the membrane, construction and disassembly of protein complexes, and modulation of protein control, are carried out by DnaJ homolog subfamily A member 1 (DNAJA1), which belongs to the DnaJ heat‐shock protein family. It is unknown if DNAJA1 regulates the production of milk in bovine mammary epithelium cells (BMECs). Methionine and leucine increased DNAJA1 expression and nuclear location, as seen by us. In contrast to DNAJA1 knockdown, overexpression of DNAJA1 boosted the production of milk proteins and fats as well as mammalian target of rapamycin (mTOR) and sterol regulatory element binding protein‐1c (SREBP‐1c). As a result of amino acids, mTOR and SREBP‐1c gene expression are stimulated, and DNAJA1 is a positive regulator of BMECs' amino acid‐induced controlled milk protein and fat production. Significance statement: The aim of this study was to investigate whether DnaJ homolog subfamily A member 1 (DNAJA1) from the DnaJ heat‐shock protein family has an effect on milk fat and milk protein synthesis in bovine mammary epithelial cells stimulated by amino acids. We found that DNAJA1 plays a positive regulatory role in milk protein and fat synthesis of bovine mammary epithelium cells and in the expression and activation of mammalian target of rapamycin and sterol regulatory element binding protein‐1c induced by amino acids. Although the exact biochemical mechanism by which amino acids promote DNAJA1 expression is unknown, stimulation of this amino acid may lead to protein alterations in DNAJA1, such as phosphorylation. Future studies must examine these underlying processes. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the foremost common cancers in women. Lactoferrin (LF) has many biological functions, such as antitumor. This study aimed to explore the regulatory effect of bovine lactoferrin (bLF) on the proliferation and apoptosis of cervical cancer HeLa cells and to clarify the potential mechanism of action of bLF against HeLa cells. This study used CCK‐8, Trypan blue staining, and colony formation assays to verify the effect of bLF on HeLa cell proliferation. Hoechst 33258 fluorescence staining, AO/EB staining, and western blotting were used to determine the effects of bLF on apoptosis and autophagy in HeLa cells. We discovered that bLF significantly reduced the proliferation of HeLa cells in a dose‐ and time‐dependent manner compared to the control group. Furthermore, bLF primarily induced apoptosis in HeLa cells by increasing the expression of the proapoptotic proteins p53, Bax, and Cleaved‐caspase‐3 and downregulating the expression of the antiapoptotic protein Bcl‐2. In addition, the present study also showed that bLF treatment significantly activated autophagy‐related proteins LC3B‐II and Beclin I and down regulated the autophagosome transporter protein p62, indicating that bLF treatment can induce autophagy in HeLa cells. After pretreatment with the autophagy inhibitor, 3‐MA, which markedly found that autophagy inhibition by 3‐MA reversed bLF‐induced apoptosis, indicating that bLF can induce apoptosis by activating intracellular autophagy in HeLa cells. In the present study, our results support the theory of bLF significantly inhibited the proliferation of Hela cells by promoting apoptosis and reinforcing autophagy. The study will play an important role in therapying cervical cancer. Significance statement: Cervical cancer is one of the most common cancers in women, and the way it is currently treated clinically inevitably has specific adverse effects. Therefore, the antitumor effects of natural active ingredients are a current research hotspot. In this study, we examined the antiproliferative effects of bovine LF (bLF) on HeLa cells. We found that bLF significantly reduced HeLa cells viability, and induced apoptosis and autophagy. In addition, we explored the association between bLF‐induced apoptosis and autophagy. Taken together, the present study demonstrated that bLF significantly inhibited the growth of HeLa cells in vitro by inducing apoptosis and activating autophagy. This study provides a theoretical basis for the treatment of cervical cancer by bLF. [ABSTRACT FROM AUTHOR]

In order to improve the physicochemical stability of soy protein isolate (SPI) emulsion, lactoferrin (LF) was used to modify the interface layer. The stable multilayer emulsion can be formed when the content of lactoferrin is 0.5% at pH 5. The emulsion with good stability was at pH 3–7, and it was also stable to temperature change. The FFAs release of SPI emulsion and LF‐SPI emulsion was 103.9% and 103.7%, respectively. The results showed that the lactoferrin layer did not hinder the digestion of oil and the bioaccessibility of carotenoids, but lactoferrin layer improved the physicochemical stability of SPI emulsions. This work provides information valuable in the design of emulsion formulations for applications in the food, pharmaceutical, and personal care industries. [ABSTRACT FROM AUTHOR]

Proteins in tears, including human lactoferrin (HLF), can be deposited and denatured on contact lenses, increasing the risk of microbial cell attachment to the lens and ocular complications. The surfactants currently used in commercial contact lens care solutions have low clearance ability for tear proteins. Chitosan oligosaccharide (COS) binds to a variety of proteins and has potential for use in protein removal, especially in contact lens care solutions. Here, we analyzed the interaction mechanism of COSs hydrolyzed from chitosan from different resources with HLF. The molecular weights (MWs) and concentrations of COSs were key factors for the formation of COS–HLF complexes. Lower MWs of COSs could form more stable COS–HLF complexes. COS from Aspergillus ochraceus had a superior effect on HLF compared with COS from shrimp and crab shell with the same MWs. In conclusion, COSs could bind to and cause a conformational change in HLF. Therefore, COSs, especially those with low MWs, have potential as deproteinizing agents in contact lens care solution. [ABSTRACT FROM AUTHOR]

SETD7 (SET7/9, KMT7) is a lysine methyltransferase that targets master regulators of cell proliferation and differentiation. Here, the impact of inhibiting SETD7 catalytic activity on mammary epithelial cell differentiation was studied by focusing on genes associated with epithelial differentiation, lactogenesis, and lipid metabolism in HC11 and EpH4 cell lines. Setd7 mRNA and protein levels were induced upon lactogenic differentiation in both cell lines. Inhibition of SETD7 activity by the compound (R)‐PFI‐2 increased cell proliferation and downregulated E‐cadherin, beta‐catenin, lactoferrin, insulin‐like growth factor binding protein 5, and beta‐casein levels. In addition, inhibition of SETD7 activity affected the lipid profile and altered the mRNA expression of the phospholipid biosynthesis‐related genes choline phosphotransferase 1, and ethanolamine‐phosphate cytidylyltransferase. Altogether, the results suggest that inhibiting SETD7 catalytic activity impairs mammary epithelial and lactogenic differentiation. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the diagnostic efficacies of selected inflammatory and intestinal biomarkers in cases of infectious and non‐infectious diarrhoea in dogs. Methods: A total of 60 dogs, 12 healthy (Control Group) and 48 with diarrhoea were used. Viral, Bacterial, Parasitic (infectious) and Nutritional diarrhoea (non‐infectious) subgroups (n: 12) were formed according to the aetiology, on the basis of clinical and laboratory examinations. Selected inflammatory and intestinal biomarkers (Calgranulin, S100A12; Lactoferrin, LCTF; C‐reactive protein, CRP) were measured both in serum and faecal samples. Results: Compared to the Control and Nutritional Diarrhoea groups, the infectious diarrhoea groups had higher serum S100A12, LCTF, CRP, blood urea nitrogen, creatinine (CR), alanine transaminase and alkaline phosphatase, and lower glucose (GLU), sodium (Na) and potassium (K) concentrations (p < 0.05); Viral and Parasitic Diarrhoea groups had lower serum albumin (ALB) and total protein (TP) concentrations (p < 0.05). Faecal S100A12, LCTF and CRP concentrations were higher in infectious diarrhoea groups compared to the Control and Nutritional Diarrhoea groups (p < 0.05). Faecal LCTF and CRP concentrations were higher in the Bacterial Diarrhoea group than in the Viral and Parasitic Diarrhoea groups (p < 0.05). Clinical significance: It was determined that serum (area under curve, AUC: 0.842 and 0.956) and faecal (AUC: 0.975 and 0.786) S100A12 and CRP concentrations in viral diarrhoea; serum (AUC: 0.956) and faecal (AUC: 0.992) LCTF concentrations in bacterial diarrhoea have diagnostic values in the diagnosis of the presence of intestinal inflammation and damage and can be used in the differential diagnosis of infectious and non‐infectious diarrhoea. [ABSTRACT FROM AUTHOR]

This work presents research about [Cr(phen)3]3+ and [Ru(phen)3]2+ interaction with human lactoferrin (HLf), a key carrier protein of ferric cations. The photochemical and photophysical properties of [Cr(phen)3]3+ and [Ru(phen)3]2+ have been widely studied in the last decades due to their potential use as photosensitizers in photodynamic therapy (PDT). The behavior between the complexes and the protein was studied employing UV–visible absorption, fluorescence emission and circular dichroism spectroscopic techniques. It was found that both complexes bind to HLf with a large binding constant (Kb): 9.46 × 104 for the chromium complex and 4.16 × 104 for the ruthenium one at 299 K. Thermodynamic parameters were obtained from the Van't Hoff equation. Analyses of entropy (ΔS), enthalpy (ΔH) and free energy changes (ΔG) indicate that these complexes bind to HLf because of entropy‐driven processes and electrostatic interactions. According to circular dichroism experiments, no conformational changes have been observed in the secondary and tertiary structure of the protein in the presence of any of the studied complexes. These experimental results suggest that [Cr(phen)3]3+ and [Ru(phen)3]2+ bind to HLf, indicating that this protein could act as a carrier of these complexes in further applications. [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf) is an oral‐pharmaceutical protein with a variety of biological activities that have attracted the attention of scientists today. In this study, Lf was nano‐encapsulated in chitosan biopolymer by ion gelation method with a concentration of 2.5 mg/ml of chitosan and 0.2 and 0.5 mg/ml of Lf and some physicochemical properties were evaluated using zeta potential, DLS, AFM, and SEM. Also, its stability against digestive enzymes such as pepsin and trypsin and its antibacterial effect compare to Lf on Escherichia coli were investigated. The result showed that the mean size of nano‐encapsulated lactoferrin (NE‐Lf) was 129.6 and 654.6 nm as well as zeta potential, +3.6 and −2.3 mV for 0.2 and 0.5 mg/ml Lf, respectively. SEM and AFM image analysis of NE‐Lf showed uniform surfaces, cubic, and homogeneous in shape, as well asdispersion stability of the nanoparticles. NE‐Lf had greater stability against the digestion of pepsin and trypsin than Lf. The efficiency of Lf encapsulation in chitosan was 75%. Both NE‐Lf and Lf showed that they were able to reduce the growth of E. coli in a dose‐dependent manner. EN‐Lf was prepared in a simpler way and in lower concentrations of chitosan and Lf than previous methods. [ABSTRACT FROM AUTHOR]

Lactoferrin, IGF‐1 and IgG are three well‐known bioactive proteins found in bovine colostrum. We studied the effects of these three active ingredients on the levels of eight cytokines in serum and on the cellular communication networks in vivo by oral administration, intraperitoneal injection and intravenous injection. The results suggested that bioactive ingredients, especially biomacromolecules, can induce different effects, even opposite effects, on the immune system depending on the route of administration. These effects are related to both the functions of the bioactive ingredient in vivo and to its specific receptor binding in the gastrointestinal mucosa that activates different signalling pathways. [ABSTRACT FROM AUTHOR]

Background: Lactoferrin is a versatile protein with important modulatory functions in inflammation and immune response. This glycoprotein can bind and sequester iron and LPS, thereby intervening in certain signaling pathways and biological processes. In the present meta‐analysis, we aimed to pool experimental data regarding the immunomodulatory effects of lactoferrin and its derived peptides on the NF‐κB signaling pathway. Materials: We searched PubMed, Google Scholar, and Web of Science databases and obtained all related articles published before April 2022. Finally, 25 eligible studies were selected, and their reports were analyzed. Methods: We used Review Manager Version 5.2 to compute the standardized mean difference (SMD) and its 95% confidence interval. In addition, the source of heterogeneity was explored using meta‐regression and sensitivity analysis. The symmetry of the funnel plot and Egger's test were also used to evaluate publication bias utilizing Comprehensive Meta‐Analysis Version 2. Results: Comparing the group of cells and animals exposed to lipopolysaccharide alone with the group that received pretreatment with lactoferrin and its derivatives, we observed significant reductions in TNF‐α, IL‐1 beta, and IL‐6 levels by 8.73 pg/mL, 2.21 pg/mL, and 3.24 pg/mL, respectively, in the second group. Additionally, IKK‐β, p‐IκB, and NF‐κB (p65) levels were significantly lower by 7.37‐fold, 15.02‐fold, and 3.88‐fold, respectively, in various cells and tissues. Conclusion: Based on the results of this meta‐analysis, lactoferrin and its derived peptides can be considered potent prophylactic and therapeutic candidates against inflammation‐associated diseases by targeting the NF‐kB pathway. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency and iron deficiency anemia are common in pediatric inflammatory bowel disease and often require supplementation with iron. There is a paucity of literature regarding optimal iron formulation. The aim of this study is to compare outcomes in pediatric patients with inflammatory bowel disease receiving either iron sucrose or ferric carboxymaltose during inpatient hospitalizations. Methods: This was a single‐center retrospective study of pediatric patients with inflammatory bowel disease admitted for newly diagnosed disease or flare who received either iron sucrose or ferric carboxymaltose. Linear regression was used to assess differences in iron repletion. Longitudinal linear mixed‐effects models and generalized estimating equations compared hematologic and iron outcomes 6 months post–iron repletion. Results: Thirty patients received ferric carboxymaltose. Sixty‐nine patients received iron sucrose. Baseline hemoglobin and iron deficits were similar in both groups. A larger percentage of iron deficit was repleted in the ferric carboxymaltose group (81.4%) compared with iron sucrose (25.9%) (P < 0.001) with fewer infusions. Cumulative doses of ferric carboxymaltose administered (18.7 mg/kg) were higher than iron sucrose (6.1 mg/kg) (P < 0.001). Hemoglobin increased more quickly with ferric carboxymaltose compared with iron sucrose (P = 0.04 and P = 0.02, respectively). Total iron binding capacity and red cell distribution width levels decreased more over time with ferric carboxymaltose vs iron sucrose (P < 0.01 and P = 0.01, respectively). No adverse effects were seen. Conclusions: Hematologic and iron parameters responded more quickly with fewer infusions in patients who received ferric carboxymaltose vs iron sucrose. Patients who received ferric carboxymaltose achieved a higher percentage of iron deficit repleted. [ABSTRACT FROM AUTHOR]

The global pandemic of COVID‐19 is considered one of the most catastrophic events on earth. During the pandemic, food ingredients may play crucial roles in preventing infectious diseases and sustaining people's general health and well‐being. Animal milk acts as a super food since it has the capacity to minimize the occurrence of viral infections due to inherent antiviral properties of its ingredients. SARS‐CoV‐2 virus infection can be prevented by immune‐enhancing and antiviral properties of caseins, α‐lactalbumin, β‐lactoglobulin, mucin, lactoferrin, lysozyme, lactoperoxidase, oligosaccharides, glycosaminoglycans, and glycerol monolaurate. Some of the milk proteins (i.e., lactoferrin) may work synergistically with antiviral medications (e.g., remdesivir), and enhance the effectiveness of treatment in this disease. Cytokine storm during COVID‐19 can be managed by casein hydrolyzates, lactoferrin, lysozyme, and lactoperoxidase. Thrombus formation can be prevented by casoplatelins as these can inhibit human platelet aggregation. Milk vitamins (i.e., A, D, E, and B complexes) and minerals (i.e., Ca, P, Mg, Zn, and Se) can have significantly positive effects on boosting the immunity and health status of individuals. In addition, certain vitamins and minerals can also act as antioxidants, anti‐inflammatory, and antivirals. Thus, the overall effect of milk might be a result of synergistic antiviral effects and host immunomodulator activities from multiple components. Due to multiple overlapping functions of milk ingredients, they can play vital and synergistic roles in prevention as well as supportive agents during principle therapy of COVID‐19. [ABSTRACT FROM AUTHOR]

The study investigated potential changes in bioactive milk proteins in relation to the season, breed, farm and udder health status. Nine hundred and sixty bulk milk samples from 12 commercial farms in northwest China were collected during 2020–2021. Six bioactive proteins including fraction of β‐casein proteins, α‐lactalbumin, β‐lactoglobulin, lactoferrin (Lf) and osteopontin were evaluated. It was found that most proteins (with exception of β‐casein A1) of Jersey cows are significantly higher than Holstein cows. Most bioactive proteins demonstrated seasonal variation, and some exhibited geographical variation (with exception of whey albumins). The milk somatic cell count showed a positive correlation with immune proteins such as Lf. [ABSTRACT FROM AUTHOR]

Galaxolide (1,3,4,6,7,8‐hexahydro‐4,6,6,7,8‐hexamethylcyclopenta‐γ‐2‐benzopyrane; HHCB) and Tonalide (7‐acetyl‐1,1,3,4,4,6‐hexamethyl‐1,2,3,4‐tetrahydronaphthalene; AHTN) are "pseudo‐persistent" pollutants that can cause DNA damage, endocrine disruption, organ toxicity, and reproductive toxicity in humans. HHCB and AHTN are readily enriched in breast milk, so exposure of infants to HHCB and AHTN is of concern. Here, the molecular mechanisms through which HHCB and AHTN interact with human lactoferrin (HLF) are investigated using computational simulations and spectroscopic methods to identify indirectly how HHCB and AHTN may harm infants. Molecular docking and kinetic simulation studies indicated that HHCB and AHTN can interact with and alter the secondary HLF structure. The fluorescence quenching of HLF by HHCB, AHTN was static with the forming of HLF‐HHCB, HLF‐AHTN complex, and accompanied by non‐radiative energy transfer and that 1:1 complexes form through interaction forces. Time‐resolved fluorescence spectroscopy indicated that binding to small molecules does not markedly change the HLF fluorescence lifetime. Three‐dimensional fluorescence spectroscopy indicated that HHCB and AHTN alter the peptide chain backbone structure of HLF. Ultraviolet‐visible absorption spectroscopy, simultaneous fluorescence spectroscopy, Fourier‐transform infrared spectroscopy, and circular dichroism spectroscopy indicated that HHCB and AHTN change the secondary HLF conformation. Antimicrobial activity experiments indicated that polycyclic musks decrease lactoferrin activity and interact with HLF. These results improve our understanding of the mechanisms involved in the toxicities of polycyclic musks bound to HLF at the molecular level and provide theoretical support for mother‐and‐child health risk assessments. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore the anti‐inflammatory and anti‐lipid effects of lactoferrin on SZ95 human sebaceous gland cells and mouse model of acne. Methods: SZ95 cells were co‐cultured with different concentrations of lactoferrin, and cell viability was determined using the 2,5‐diphenyl‐2H‐tetrazolium bromide method. Oil red O and Nile red staining were performed to determine the lipid content. The mRNA expression of genes related to lipid metabolism (sterol regulatory element‐binding protein‐1 [SREBP‐1], fatty acid synthase [FAS], stearoyl‐CoA desaturase‐1 [SCD‐1], fatty acid desaturase 2 [FADS2]) and inflammation (interleukin‐8 [IL‐8]) was determined by reverse transcription–polymerase chain reaction. An acne mouse model was established using injection of P. acnes on the backs of mice. The proliferation and apoptosis of sebaceous gland cells were examined by immunohistochemistry against proliferating cell nuclear antigen (PCNA) and TUNEL staining, respectively. Western blotting was used to detect FADS2 and CXCL15 protein expression. Results: Lactoferrin treatment at 10–500 μg/ml significantly decreased the lipid content, as revealed by the oil red O and Nile red staining. It also attenuated the increase of mRNA expression of SREBP‐1, FAS, SCD‐1, FADS2, and IL‐8 in insulin‐treated SZ95 cells. Moreover, lactoferrin treatment at the doses of 1–50 mg/mouse significantly reduced the inflammation and lipid production in the mouse model of acne. Also, the number of sebaceous gland cells was significantly reduced, and apoptosis was significantly increased by lactoferrin treatment in the mice. Mechanically, the levels of FADS2 and CXCL15 proteins in tissues were significantly decreased after lactoferrin treatment in the model mice. Conclusion: Our results demonstrate the potential of lactoferrin against sebogenesis, sebaceous gland inflammation in acne. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a global gastrointestinal disorder closely related to psychological stress exposure and local colonic inflammation. Herein, we investigated the effect of wrap‐restraint stress (WRS) on rat behavior, on adenosine monophosphate‐activated protein kinase–mammalian/mechanistic target of rapamycin–signal transducer and activator of transcription 3 (AMPK–mTOR–STAT3) signaling, and autophagy in colonic mucosa. The impact of chronic administration of vitamin D3 and lactoferrin was compared. Twenty‐four male Wistar rats were randomly divided into four groups. Chronic WRS protocol was applied as a rodent model of IBS. Group I: naïve animals, Group II: WRS animals, Group III: WRS‐exposed and treated with vitamin D3 (500 IU/kg/day), and Group IV: WRS‐exposed and treated with lactoferrin (300 mg/kg/day). In this study, we found that chronic administration of each of vitamin D3 and lactoferrin resulted in a significant increase in social interaction test, interleukin‐10, AMPK, optical density of LC3B, goblet cell count and marked decrease in serum cortisol level, STAT3, inflammatory cell count, and optical density of mTOR in comparison to the WRS rats. Our findings suggest that both vitamin D3 and Lactoferrin could augment colonic autophagy through enhanced AMPK expression and inhibition of mTOR–STAT3 signaling, which offers practical insights into their clinical use in the prevention and therapy of IBS. However, lactoferrin intake as a nutritional supplement could be more helpful for stress‐induced colitis treatment than vitamin D3. Significance Statement: Irritable bowel syndrome is a common disease whose incidence is uprising due to chronic life stressors exposure. The need for the intake of dietary supplements that could alleviate IBS symptoms has long been proposed. In the present study, we compared the chronic oral intake of vitamin D3 to lactoferrin in animals exposed to experimental colitis and examined their effects at behavioral and tissue levels. We investigated their effects on the adenosine monophosphate‐activated protein kinase–mammalian/mechanistic target of rapamycin–signal transducer and activator of transcription (AMPK–mTOR–STAT3) signaling and autophagy as a trial to give us more understanding about the molecular pathology of IBS in the colon. Both drugs improved colitis, through lactoferrin seemed more effective. Future research could be directed to explore other drugs that target AMPK–mTOR–STAT3 signaling and autophagy to lessen IBS patients suffering. [ABSTRACT FROM AUTHOR]

Glioma is one of the most aggressive malignant diseases for human health. It is difficult to resect completely due to their invasiveness. The targeted delivery, as a noninvasive approach, is a major strategy for the development of treatments for brain tumors. Lactoferrin (Lf) receptors are over‐expressed in both brain endothelial cells and glioma cells. Macromolecular Lf modified nanoparticles have been shown to enhance the brain targeting. Muscone is a "guide" drug that have been demonstrated to promote liposomes into the brain by modification. To further enhance the brain‐targeting efficacy of Lf modified carriers, we designed that Lf and muscone dual‐modified liposomes cross blood–brain barrier (BBB) and target to brain for enhanced docetaxel (DTX) brain delivery. The results showed that we successfully prepared Lf and muscone dual‐modified liposomes (Lf‐LP‐Mu‐DTX), the number of Lf molecules connected to the surface of per liposome was 28. Lf‐LP‐Mu‐DTX increased uptake in both U87‐MG cells and hCMEC/D3 cells, enhanced penetration of U87‐MG tumor spheroid and in vitro BBB model, had better in vitro and in vivo anti‐tumor effects. In conclusion, "guide" of muscone modification enhanced brain‐targeting efficacy of Lf modified liposomes, Lf and muscone dual‐modified docetaxel loaded liposomes present a potential brain‐targeting drug delivery system for use in the future treatment of gliomas. [ABSTRACT FROM AUTHOR]

The antioxidant and the lipase and the angiotensin‐converting enzyme (ACE) inhibitory properties of camel lactoferrin and its hydrolysates elaborated with four proteolytic enzymes (trypsin, α‐chymotrypsin, pancreatin and papain) were assessed. Lactoferrin was purified from camel colostrum using cation exchange chromatography. Camel lactoferrin hydrolysates showed different degrees of hydrolysis, reverse phase‐HPLC profiles and molecular weight distributions, reflecting heterogeneity in terms of polarity and molecular weight of the generated peptides. Camel lactoferrin hydrolysates exhibited higher antioxidant, lipase and ACE inhibitory activities than native lactoferrin. Pancreatin‐generated hydrolysates showed the highest lipase inhibitory activity (48.1%), while papain‐generated hydrolysates presented the greatest ACE inhibitory activity (89.14%). [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the influence of dietary supplementation of bovine lactoferrin (bLF) on growth performance, carcass traits, histomorphology of jejunum, immune function and hepatic and splenic gene expression of interferon‐gamma (IFN‐γ) and interleukine‐2 (IL‐2) in broiler chickens. A total of 240 one‐day‐old Ross 308 male broiler chickens were randomly allotted into six dietary treatments with four replicate pens (10 chicks per pen) and fed experimental diet in 3 feeding phases (starter: d 0–10, grower: d 11–24 and finisher: d 25–42). The experimental treatments were (1) corn–soya bean meal‐based basal diet (control), (2–5) basal diet supplemented with 200, 400, 600, 800 mg/kg bLF, respectively, and (6) basal diet supplemented with 200 mg/kg oxytetracycline (OTC). The average body weight gain (ABWG) of broilers fed 800 mg/kg bLF was 8.48% higher than those fed a corn–soybean meal‐based diet during the starter period (d 0–10) (linear effect, p = 0.002; quadratic effect, p = 0.24). Average daily feed intake (ADFI) and the feed conversion ratio (FCR) were not affected (p>0.05) by bLF supplementation. At 42 days of age, the breast meat percentage and carcass yield of broilers fed 800 mg/kg bLF compared with the control group significantly increased by 9.51% and 6.03% respectively (p < 0.05). Compared with the chicks fed the control diet, the chicks fed diets supplemented with bLF had higher villus height, muscle thickness and villus surface area (p > 0.05). Dietary bLF inclusion increased the total immunoglobulin (IgT) titre against sheep red blood cells (SRBCs) antigen (linear effect, p = 0.031; quadratic effect, p = 0.035) and improved the phytohaemagglutinin‐P (PHA‐P)‐skin test of broilers. Compared with the control, bLF enhanced the gene expression of IFN‐γ in spleen (p = 0.048, linear effect, p = 0.009; quadratic effect, p = 0.093) and liver (p = 0.012, linear effect, p = 0.008; quadratic effect, p = 0.01) and IL‐2 expression in spleen (p = 0.021, linear effect, p = 0.026; quadratic effect, p = 0.103). The bLF supplementation had no effect on IL‐2 gene expression in liver (p > 0.05, linear effect, p = 0.213; quadratic effect, p = 0.159). In conclusion, we found that supplementation of broiler diets with 800 mg/kg bLF can improve the growth performance, carcass yield, cell‐mediated and antibody‐mediated immune responses and enhance the IL‐2 and IFN‐γ gene expression of broilers. [ABSTRACT FROM AUTHOR]

We recently reported that lactoferrin (LF) induces Foxp3+ Treg differentiation through binding to TGFβ receptor III (TβRIII), and this activity was further enhanced by TGFβ1. Generally, a low T‐cell receptor (TCR) signal strength is favourable for Foxp3+ Treg differentiation. In the present study, we explored the effect of lactoferrin chimera (LFch, containing lactoferricin [aa 17–30] and lactoferrampin [aa 265–284]), along with TGFβ1 on Foxp3+ Treg differentiation. LFch alone did not induce Foxp3 expression, yet LFch dramatically enhanced TGFβ1‐induced Foxp3 expression. LFch had little effect on the phosphorylation of Smad3, a canonical transcriptional factor of TGFβ1. Instead, LFch attenuated the phosphorylation of S6 (a target of mTOR), IκB and PI3K. These activities of LFch were completely abrogated by pretreatment of LFch with soluble TGFβ1 receptor III (sTβRIII). Consistent with this, the activity of LFch on TGFβ1‐induced Foxp3 expression was also abrogated by treatment with sTβRIII. Finally, the TGFβ1/LFch‐induced T cell population substantially suppressed the proliferation of responder CD4+ T cells. These results indicate that LFch robustly enhances TGFβ1‐induced Foxp3+ Treg differentiation by diminishing TCR/CD28 signal intensity. [ABSTRACT FROM AUTHOR]

Breast milk has been found to inhibit coronavirus infection, while the key components and mechanisms are unknown. We aimed to determine the components that contribute to the antiviral effects of breastmilk and explore their potential mechanism. Lactoferrin (Lf) and milk fat globule membrane inhibit severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐related coronavirus GX_P2V and transcription‐ and replication‐competent SARS‐CoV‐2 virus‐like particles in vitro and block viral entry into cells. We confirmed that bovine Lf (bLf) blocked the binding between human angiotensin‐converting enzyme 2 and SARS‐CoV‐2 spike protein by combining receptor‐binding domain (RBD). Importantly, bLf inhibited RNA‐dependent RNA polymerase (RdRp) activity of both SARS‐CoV‐2 and SARS‐CoV in vitro in the nanomolar range. So far, no biological macromolecules have been reported to inhibit coronavirus RdRp. Our result indicated that bLf plays a major role in inhibiting viral replication. bLf treatment reduced viral load in lungs and tracheae and alleviated pathological damage. Our study provides evidence that bLf prevents SARS‐CoV‐2 infection by combining SARS‐CoV‐2 spike protein RBD and inhibiting coronaviruses' RdRp activity, and may be a promising candidate for the treatment of coronavirus disease 2019. [ABSTRACT FROM AUTHOR]

Objective: Lactoferrin is an 80 KDa iron‐binding glycoprotein that plays a significant role in the innate immune system and is considered to be an important microbicide molecule. This study aimed to assess the concentration of lactoferrin in Schistosoma mansoni‐infected cases before and after praziquantel treatment. Methods: A cross‐sectional study was carried out on 250 individuals aged from 5 to 30 years. Stool samples were examined for the presence of parasitic infections using Kato‐Katz and formalin ethyl acetate techniques. All S. mansoni‐positive cases were treated with praziquantel and stool samples were recollected 21 days later. Faecal lactoferrin level was determined before and after treatment. Results: The prevalence of S. mansoni infection was 14.4%. Among 36 participants infected with S. mansoni, the cure rate was 91.7%. A statistically significant difference in the mean lactoferrin level before and after treatment was detected (1648.95 pg/ml ± 656.5 vs. 1162.8 pg/ml ± 356.8). This difference was statistically significant in the middle and older age groups, in males and in the absence of coinfection with other parasites. Conclusion: Lactoferrin could be a promising biomarker associated with S. mansoni infection, however, it could not be used to assess the severity of infection. [ABSTRACT FROM AUTHOR]

Background: Milk lactoferrin is a multi‐functional, iron‐binding glycoprotein with immunomodulatory effects, protecting infants against infectious diseases. Aims: 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. Materials & Methods: 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. Results: 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. Discussion & Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Lactoferrin is a multifunctional protein that has roles in iron metabolism, cell generation and differentiation, and antibacterial, antiviral, and antiparasitic activity. The study aim was to evaluate the effect of dietary lactoferrin powder on the innate immune response and disease resistance of silver carp (Hypophthalmichthys molitrix) infected with Vibrio vulnificus. The study also investigates immune cells in different organs including gills, intestine, spleen, liver, and pancreas using light, scan electron microcopy. Two diet regimes, a basic diet and a 600‐mg/kg bovine lactoferrin‐supplemented diet were used. The fish were fed for 30 successive days. We included 270 apparently healthy silver carp (H. Molitrix) with an average body weight of 10 ± 2 g/fish. Addition of lactoferrin to the diet led to an increase in the activity of non‐specific immune parameters; lymphocytes, and in the monocytes percentage, and in total protein, serum globulin, and albumin, with a corresponding increase in phagocytic activities and indices. The histological analysis revealed increase immune cells such as lymphocytes in intestine, rodlet cells in liver, gills, and pancreas, and the macrophages in liver, pancreas as well as spleen. The lactoferrin‐supplemented diet significantly increased survival and disease resistance following V. vulnificus challenge, which seemed to correspond to an enhancement of non‐specific immune functions in H. molitrix. Research Highlights: The study evaluates the effect of dietary lactoferrin powder on the innate immune response and disease resistance of silver carp (Hypophthalmichthys molitrix) infected with Vibrio vulnificus.The study also investigates immune cells in different organs including gills, intestine, spleen, liver, and pancreas using light, scan electron microcopy.Lactoferrin increases the activity of nonspecific immune parameters; lymphocytes, and in the monocytes percentage, and in total protein, serum globulin, and albumin, with a corresponding increase in phagocytic activities and indices.The histological analysis revealed increase immune cells such as lymphocytes in intestine, rodlet cells in liver, gills, and pancreas, and the macrophages in liver, pancreas as well as spleen. [ABSTRACT FROM AUTHOR]

The rapid clearance of apoptotic cells (ACs), known as efferocytosis, prompts the inhibition of inflammatory responses and autoimmunity and maintains homeostatic cell turnover by controlling the release of intracellular contents. The fast clearance of ACs requires professional and nonprofessional phagocytic cells that can accurately and promptly recognize ACs and migrate towards them. Cells undergoing apoptosis alarm their presence by releasing special soluble chemotactic factors, such as lactoferrin, that act as "Find me," "Keep out," or "Stay away" signals to recruit phagocytic cells, such as macrophages or prevent granulocyte migration. Efferocytosis effectively serves to prevent damage‐associated molecular pattern release and secondary necrosis and inhibit inflammation/autoimmunity at the very first step. Since less attention has been given to the cross‐talk and balance of "Find me" and "Keep out" signals released from ACs in efferocytosis, we set out to investigate the current knowledge of the roles of "Find me" and "Keep out" signals in the efferocytosis process. [ABSTRACT FROM AUTHOR]

Milk samples were collected from 140 individual dromedary camels (Camelus dromedarius) to determine the variability in the concentrations of several bioactive whey proteins. The ranges were as follows: insulin (IN) (17.8–51.1 mIU/L), insulin‐like growth factor I (IGF1) (1.4–736.1 ng/mL), insulin‐like growth factor II (IGF2) (13.7–82.6 ng/mL), lactoferrin (639.4–2094.9 µg/mL), immunoglobulin G (IgG) (7.3–17.9 mg/mL), peptidoglycan recognition protein‐1 (PGRP‐1) (1.6–22.3 ng/mL), lysozyme (LZ) (23.3–71.4 µg/mL) and lactoperoxidase (LPO) (7.1–15.5 ng/mL). These data demonstrate wide variation in the concentrations of the studied proteins. Significant correlations (P < 0.05) were observed between the concentrations of IN and LZ, IN and IgG, IN and PGRP‐1, LZ and PGRP‐1, IgG and LPO, and IgG and PGRP‐1. [ABSTRACT FROM AUTHOR]

Protein fractionation and purification remain challenging in membrane separation. Herein, a pH‐responsive membrane was developed by grafting the brush‐like poly(dimethylaminoethyl methacrylate) (PDMAEMA) via ATRP onto the ethylene vinyl alcohol copolymer (EVAL) membrane for protein fractionation. The PDMAEMA brushes are distributed in all pore channels of the membrane. Based on the electrostatic and sieving properties of the as‐prepared pH‐responsive membrane, three milk proteins are successfully separated from their mixture. The α‐Lactalbumin (α‐LA) preferentially permeates the membrane from the mixture at pH 3.2, and the bovine serum albumin (BSA) and lactoferrin (LF) can be separated at pH 6.4 based on the selective adsorption. This work proposes a promising candidate for protein separation by a pH‐responsive membrane. [ABSTRACT FROM AUTHOR]

BACKGROUND Iron deficiency and iron overload can affect the normal functioning of the innate and adaptive immune responses. Fermented milk products may enhance immune functions, but little is known about the effect of fermented milks on modulation of the immune response during iron deficiency anemia and recovery with normal or high dietary iron intake. Eighty male Wistar rats were randomly assigned to a control group fed a standard diet or to an anemic group fed a diet deficit in iron. Control and anemic groups were fed for 30 days with diets based on a fermented goat's or cow's milk product, with normal iron content or iron overload. RESULTS: In general, during anemia recovery lectin and alternative complement pathway activity and lactoferrin decreased, because it improves iron homeostasis, which is critically important in immune system functions. Fermented goat's milk diet enhanced immune function during iron deficiency recovery, suppressed oxidant‐induced eotaxin and fractalkine expression due to the concurrent reduction of free radical production and pro‐inflammatory cytokines, and decreased monocyte chemoattractant protein‐1 and monocyte migration and adhesion. The increase in interferon‐γ can confer immunological colonization of gut microbiota and downregulate inflammation. CONCLUSION: Fermented goat's milk consumption enhances immune function, modifying complement pathway activity and decreasing pro‐inflammatory cytokines as well as lactoferrin concentration, due to the improvement of iron homeostasis, which is critically important in the normal function of the immune system. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Summary: It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our systematic review aimed at identifying the effects of orally administered LF against virus infections. The systematic search was conducted on PubMed, Scopus, Web of Science, BioRxiv.org and ClinicalTrials.gov from database inception to 7th January 2021. Eligible articles investigated any virus family and provided data on the effects of orally administered LF of any origin in the prevention and/or management of confirmed viral infections in people of any age. A narrative synthesis of the results was performed. Quality was assessed with the Cochrane Risk‐Of‐Bias and ROBINS‐1 tools. A total of 27 records were included, nine of which were registered protocols. We found data on Flaviviridae (n = 10), Retroviridae (n = 3), Coronaviridae (n = 2), Reoviridae (n = 2) and Caliciviridae (n = 1). Most published trials were at high risk of bias. The findings were heterogeneous across and within viral families regarding virological, immunological and biological response, with no clear conclusion. Some weak but positive results were reported about decrease of symptom severity and duration, or reduction in viral loads. Despite high tolerability, the effects of LF as oral supplement are still inconsistent, both in preventing and managing viral infections. Small sample sizes, variety in recruitment and treatment protocols, and low study quality may have contributed to such heterogeneity. Better‐designed studies are needed to further investigate its potential benefits against viral infections, including SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

Background: Mammalian meat is the most common trigger of the allergic reactions in patients with α‐Gal syndrome (AGS). Milk and dairy, although less often, also cause a significant number of allergic manifestations. The aim of this study was to identify α‐Gal‐containing bovine milk proteins with allergenic properties among AGS patients. Methods: Thirty‐eight AGS patients with IgE to milk were included in the study. Milk proteins were analyzed for the presence of α‐Gal and for binding by patients' IgE using immunoblot, ImmunoCAP, and inhibition ELISA. Allergenicity of milk and milk proteins was assessed by basophil activation test. Results: More than half of the AGS patients reported allergic reactions to milk or dairy products. Bovine γ‐globulin (BGG), lactoferrin (LF), and lactoperoxidase (LPO) were identified as α‐Gal carrying proteins which were recognized by AGS patients' IgE. Whey mirrored the anti‐α‐Gal and IgE reactivity of BGG, LF, and LPO. Eighty‐nine percent of the patients displayed IgE to BGG, 91% to LF, and 57% to LPO. Inhibition of α‐Gal‐specific IgE binding was achieved by BGG, LF, LPO, and whey. These proteins also activated AGS patients' basophils. Interestingly, at lower concentrations, LF was the most potent inhibitor of IgE binding, and the most potent activator of basophils. Conclusion: BGG, LF, and LPO were all found to be relevant milk α‐Gal‐containing glycoproteins that bound AGS patients' IgE antibodies and activated their basophils. These proteins are probably involved in the allergic reactions to milk in AGS patients. LPO was for the first time shown to be an allergen. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are located in various tissues where these cells show niche‐dependent multilineage differentiation and secrete immunomodulatory molecules to support numerous physiological processes. Due to their regenerative and reparative properties, MSCs are extremely valuable for cell‐based therapy in tackling several pathological conditions including COVID‐19. Iron is essential for MSC processes but iron‐loading, which is common in several chronic conditions, hinders normal MSC functionality. This not only aggravates disease pathology but can also affect allogeneic and autologous MSC therapy. Thus, understanding MSCs from an iron perspective is of clinical significance. Accordingly, this review highlights the roles of iron and iron‐related proteins in MSC physiology. It describes the contribution of iron and endogenous iron‐related effectors like hepcidin, ferroportin, transferrin receptor, lactoferrin, lipocalin‐2, bone morphogenetic proteins and hypoxia inducible factors in MSC biology. It summarises the excess‐iron‐induced alterations in MSC components, processes and discusses signalling pathways involving ROS, PI3K/AKT, MAPK, p53, AMPK/MFF/DRP1 and Wnt. Additionally, it evaluates the endogenous and exogenous saviours of MSCs against iron‐toxicity. Lastly, it elaborates on the involvement of MSCs in the pathology of clinical conditions of iron‐excess, namely, hereditary hemochromatosis, diabetes, β‐thalassaemia and myelodysplastic syndromes. This unique review integrates the distinct fields of iron regulation and MSC physiology. Through an iron‐perspective, it describes both mechanistic and clinical aspects of MSCs and proposes an iron‐linked MSC‐contribution to physiology, pathology and therapeutics. It advances the understanding of MSC biology and may aid in identifying signalling pathways, molecular targets and compounds for formulating adjunctive iron‐based therapies for excess‐iron conditions, and thereby inform regenerative medicine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]