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This study aimed to estimate the hepatic and immune ameliorating potential of extracted bovine lactoferrin (LF), Selenium nanoparticles (SeNPs) or their combination (LF/SeNPs) against bleomycin (BLM) induced hepatic injury. Fifty adult male rats (160–200 g) were equally divided into five groups: (1) the saline control group, (2) BLM-injected (15 mg/kg twice a week, ip), and (3–5) groups treated orally with LF (200 mg/kg/day), SeNPs (0.0486 mg/kg/day) or LF/SeNPs combination (200.0486 mg/kg/day) for 6 weeks post BLM-intoxication. Blood and liver samples were subjected to biochemical, histopathological, and immunohistochemical analyses. The results revealed that BLM caused a significant increase in hepatic lipid peroxidation and nitric oxide, as well as serum markers of liver functions (AST, ALT and GGT activities), and levels of GM-CSF, CD4, TNF-α, IL-1β, TGF-β1, fibronectin, triglycerides, cholesterol and LDL-C. Additionally, hepatic glutathione, Na+/K+-ATPase, and glutathione peroxidase, as well as serum HDL-C, total protein and albumin levels were significantly reduced. Moreover, BLM injection resulted in marked histopathological alterations and severe expression of caspase 3. Post-treatment of BLM-intoxicated rats with LF, SeNPs or LF/SeNPs combination obviously improved the BLM-induced hepatic damages; this was achieved from the marked modulations in the mentioned parameters, besides improving the histopathological hepatic architecture. It is worth mentioning that LF/SeNPs exerted the greatest potency. In conclusion, the obtained results demonstrated that LF, SeNPs and LF/SeNPs succeeded in attenuating the BLM-induced hepatic dysfunction. Therefore, these supplements might be used to protect against drug-associated side effects. [ABSTRACT FROM AUTHOR]

Summary Background Aims Methods Results Conclusions 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.To conduct a systematic literature search and summarize the existing evidence for host mucosa‐derived faecal biomarkers in evaluating small intestinal damage.We searched for studies on PubMed (MEDLINE) until 1 March 2024.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.Further studies are needed to determine reliable faecal markers as a proxy for small intestinal mucosal damage. [ABSTRACT FROM AUTHOR]

Bovine lactoferrin (bLF) is a 77 kDa glycoprotein that is abundant in bovine breast milk and exerts various bioactive functions, including antibacterial and antiviral functions. Few studies have explored bLF activity against parasites. We found that bLF affects hemozoin synthesis by binding to heme, inhibiting heme iron polymerization necessary for Plasmodium berghei ANKA survival in infected erythrocytes, and also binds to hemozoin, causing it to disassemble. In a challenge test, bLF administration inhibited the growth of murine malaria parasites compared to untreated group growth. To determine whether the iron content of bLF affects the inhibition of malaria growth, we tested bLFs containing different amounts of iron (apo-bLF, native-bLF, and holo-bLF), but found no significant difference in their effects. This indicated that the active sites were located within the bLFs themselves. Further studies showed that the C-lobe domain of bLF can inhibit hemozoin formation and the growth of P. berghei ANKA. Evaluation of pepsin degradation products of the C-lobe identified a 47-amino-acid section, C-1, as the smallest effective region that could inhibit hemozoin formation. This study highlights bLF's potential as a novel therapeutic agent against malaria, underscoring the importance of its non-iron-dependent bioactive sites in combating parasite growth. [ABSTRACT FROM AUTHOR]

N‐glycans present in milk glycoproteins (e.g. lactoferrin and immunoglobulin G) can provide infants with nutritional and protective effects similar to breast milk. In this study, we enriched N‐glycoproteins from WPC 70 using ultrafiltration and anion exchange chromatography on DEAE Sepharose Fast Flow column, with N‐glycan content and N‐glycoprotein purity as evaluation indicators. The results showed that changing feed flow rate and molecular weight cut‐off was more effective to improve ultrafiltration separation than changing feed concentration. When using a 100 kDa ultrafiltration membrane with a feed flow rate of 10 rpm and a feed concentration of 10 mg/mL, N‐glycan content could be increased by 200%. However, anion exchange chromatography was more efficient for purification, increasing N‐glycan content by 700%. This study provided a reliable method for N‐glycan enrichment and a scientific basis for further research and potential application of N‐glycans in infant formula and whey products. [ABSTRACT FROM AUTHOR]

Lactoferrin is a potential anticancer protein naturally found in mammalian secretions. It shows antiproliferative effects on various cancer types in vitro and in vivo. Its activity is highly associated with the immune system and its complements. On the other hand, hyperthermia is a type of cancer therapy in which tissues are exposed to heat at a temperature in the range of 40°C-44°C which induces apoptosis and necrosis. Hyperthermia normally aims to improve the results of conventional treatment strategies such as chemo or radiotherapy. The study aimed to enhance the lactoferrin effect with hyperthermia. Hyaluronic acid was additionally used in the formulation to augment the anticancer effect of lactoferrin. MTT Assays were performed for cell viability at 24 and 72 hours after the lactoferrin, hyaluronic acid, and hyperthermia treatment on MCF-7, MDA-MB 231, and HDF cell lines in vitro. No anticancer efficacy of lactoferrin was observed. However, it was demonstrated that Hyaluronic acid enhanced the anti-proliferative efficacy of hyperthermia treatment, and significant reductions in the cell viability were observed after 24 hours on MCF-7 cells in a p53-dependent manner whereas no reduction in the cell viability of MDAMB 231 and HDF cells. Mutation on the p53 gene of MDA-MB 231 cells possibly prevented the heat-induced apoptosis. Hyaluronic acid-induced cell death was observed 72 hours after the treatment independently from the heat exposure group. No cytotoxicity was observed on the HDF cell line. The activity could not be obtained from the pure hyaluronic acid solution. Subsequent determination of the chemical responsible for the anticancer efficacy should be performed. This research could lead to the discovery of a new selective chemotherapeutic agent that can be used in breast cancer. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The presence of an autocrine factor in milk that can trigger mammary gland involution was proposed more than 50 yr ago. To provide evidence for the existence of one or more autocrine factors, 10 multiparous cows in late lactation were quarter-milked for 7 d. Following this baseline period, the right front quarter of each cow was left unmilked, and the other quarters were milked for 7 d. Before the last milking of that period, milk (mammary secretions) was collected aseptically from both front quarters. After that milking, 250 mL of the collected samples were infused in the cows' respective rear quarters. No quarters were milked for the following 7 d (milk stasis period), and quarter milking was then resumed in all quarters for the last 7 d of the experiment (remilking period). Quarter milk samples were collected during the baseline period, before the milk stasis period, and during the remilking period. These samples were used for measuring milk components and the concentration of involution markers (SCC, BSA, and lactoferrin). Samples of mammary secretions were collected manually from the quarters during the milk stasis period for involution marker determination. We extracted RNA from samples collected from front quarters before the last milking before the milk stasis period for microRNA (miRNA) determination. As anticipated, the longer milk stasis period implemented for the right front quarter resulted in a more advanced involution than in the left front quarter, based on the concentration of involution markers in the mammary secretions, lower milk production recovery, and changes in milk composition during the remilking period. All 3 involution marker concentrations in the mammary secretions increased in both rear quarters, but were greater in the right quarter secretions than in the left quarter secretions. Resuming milking reinitiated milk production in all quarters, but milk production recovery in the right rear quarters was less robust than that in the left rear quarters (54.3 ± 1.4% vs. 61.6 ± 1.4%, respectively). Milk from the quarters infused with mammary secretions (right rear) had a lower lactose content, but a higher milk protein content and higher SCC than the quarters infused with milk. We detected a total of 359 miRNAs, 76 of which were differentially expressed in milk and mammary secretions. Expression of bta-miR-221 and bta-miR-223 was upregulated in mammary secretions 34- and 40-fold, respectively. The results of the present experiment support the contention that milk stasis leads to the accumulation of one or more factors that trigger involution. The results also indicate that milk stasis leads to changes in the miRNA profile of the milk, but whether such changes are a cause or a consequence of the involution process remains to be established. [ABSTRACT FROM AUTHOR]

Objectives: The aim was to assess the associations between the LTF, MMP20, CA6, and TAS1R2 polymorphisms and caries in the Zhuang population and explore the underlying mechanism of the impact of lactoferrin on caries susceptibility. Methods: A case-control study of 315 adolescents was conducted in Guangxi, China, from May–November 2022. Data were collected through oral examinations and questionnaires. Buccal mucosa cells and DNA samples were collected using the SNPscan technique. Saliva and supragingival plaque samples were taken from 69 subjects with various LTF rs10865941 genotypes. The relationships among the LTF rs10865941 polymorphism, lactoferrin, Streptococcus mutans, and caries were investigated by using the ELISA and qRT-PCR, along with logistic regression analysis. Results: The genotype distribution of the LTF gene were significantly different between the case and control groups (p = 0.018). The case group had lower C allele and greater T allele frequencies than the control group (p = 0.006). The LTF rs10865941 polymorphism was associated with caries in the codominant, dominant, and additive models (p < 0.05). MMP20 rs1784418, CA6 rs2274328, and TAS1R2 rs35874116 were not significantly different between the two groups (p > 0.05). A greater quantity of S. mutans. in the supragingival plaque was found in the case group (p = 0.03). There were significant differences between the two groups in both the codominant model and the dominant model (p < 0.05). Conclusions: The LTF rs10865941 polymorphism may be associated with caries susceptibility in the Zhuang population of China. The LTF rs10865941 T allele may be a potential risk factor for dental caries. [ABSTRACT FROM AUTHOR]

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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]

Antibiotics, often hailed as 'miracle drugs' in the 20th century, have revolutionised medicine by saving millions of lives in human and veterinary medicine, effectively combatting bacterial infections. However, the escalating global challenge of antimicrobial resistance and the appearance and spread of multidrug-resistant pathogens necessitates research into alternatives. One such alternative could be lactoferrin. Lactoferrin, an iron-binding multifunctional protein, is abundantly present in mammalian secretions and exhibits antimicrobial and immunomodulatory activities. An often overlooked aspect of lactoferrin is its proteolytic activity, which could contribute to its antibacterial activity. The proteolytic activity of lactoferrin has been linked to the degradation of virulence factors from several bacterial pathogens, impeding their colonisation and potentially limiting their pathogenicity. Despite numerous studies, the exact proteolytically active site of lactoferrin, the specific bacterial virulence factors it degrades and the underlying mechanism remain incompletely understood. This review gives an overview of the current knowledge concerning the proteolytic activity of lactoferrins and summarises the bacterial virulence factors degraded by lactoferrins. We further detail how a deeper understanding of the proteolytic activity of lactoferrin might position it as a viable alternative for antibiotics, being crucial to halt the spread of multi-drug resistant bacteria. [ABSTRACT FROM AUTHOR]

Simple Summary: To explore molecular regulation related to lactation during pregnancy, the mammary glands of pregnant Mongolian mares during lactation and non-lactation were sequenced and analyzed for differentially expressed genes. We screened milk protein-related genes (CSN1S1, CSN3, and LALBA), genes related to the lipid metabolism process (DGAT1, LEP, and LEPR), and genes closely related to lactation events (FAT1 and LTF), which can be used as candidate genes for selecting lactation traits in Mongolian mares. To investigate molecular regulation involved in lactation during pregnancy, this study focused on the transcriptomic profiles of mammary tissue from lactating and non-lactating Mongolian mares at the second month of gestation. A total of 4197 differentially expressed genes were identified by comparing mammary tissues from pregnant mares at two different states, including 1974 differentially expressed genes such as the milk protein-related genes a-s1-casein (CSN1S1), k-casein (CSN3), lactalbumin (LALBA), and lactoferrin (LTF), which were highly expressed in the lactating mares group, and overall, these differentially expressed genes were mainly associated with biological processes such as endoplasmic reticulum protein processing, the Toll-like receptor signaling pathway, steroid biosynthesis, cytokine–cytokine receptor interactions, and amino sugar and nucleotide glycolysis. These findings serve as a foundation for investigating the molecular underpinnings of lactation in pregnant equids. [ABSTRACT FROM AUTHOR]

As a nutraceutical, bovine lactoferrin (bLf), an iron-binding glycoprotein involved in innate immunity, is gaining elevated attention for its ability to exert pleiotropic functions and to be exceptionally tolerated even at high dosages. Some of bLf's activities, including its anti-inflammatory and antioxidant, are tightly linked to its ability to both chelate iron and enter inside the cell nucleus. Here, we present data about Valpalf®, a new formulation containing bLf, sodium citrate, and sodium bicarbonate at a molar ratio of 10−3. In the present study, Valpalf® exhibits superior iron-binding capacity, resistance to tryptic digestion, and a greater capacity to accumulate into the nucleus over time when compared to the native bLf alone. In agreement, Valpalf® effectively reduces interleukin(IL)-6 levels in lipopolysaccharide-stimulated macrophages and modulates the expression of antioxidant enzymes, such as superoxide dismutase 1 and 2, in phorbol-12-myristate-13-acetate-stimulated monocytes. Of note, this potentiated bioactivity was corroborated in a retrospective study on the treatment of anemia of inflammation in hereditary thrombophilic pregnant and non-pregnant women, demonstrating that Valpalf® improves hematological parameters and reduces serum IL-6 levels to a higher extent than bLf alone. [ABSTRACT FROM AUTHOR]

This document, titled "Functional Properties of Probiotics in Food Sources," provides an overview of the benefits and applications of probiotics in various food sources. Probiotics are live microorganisms found in dairy products, fermented foods, fruits, and vegetables that offer health benefits such as improving gut health, mitigating food allergies, and enhancing exercise performance. The document also discusses the use of prebiotics and synbiotics, which combine probiotics with prebiotic ingredients, to further enhance these bioactivities. Additionally, the document includes summaries of eleven research articles that explore the effects of specific probiotic strains on various health conditions and the improvement of fermented food quality. The findings highlight the significance of probiotics in food sources and encourage further research in this area. [Extracted from the article]

Lactoferrin, a glycoprotein derived from breastmilk, is recognized for its health benefits in infants and children; however, its protective effects when administered during gestation and lactation against offspring hypertension remain unclear. This study aimed to investigate whether maternal lactoferrin supplementation could prevent hypertension in offspring born to mothers with chronic kidney disease (CKD), with a focus on nitric oxide (NO), renin–angiotensin system (RAS) regulation, and alterations in gut microbiota and short-chain fatty acids (SCFAs). Prior to pregnancy, female rats were subjected to a 0.5% adenine diet for 3 weeks to induce CKD. During pregnancy and lactation, pregnant rats received one of four diets: normal chow, 0.5% adenine diet, 10% lactoferrin diet, or adenine diet supplemented with lactoferrin. Male offspring were euthanized at 12 weeks of age (n = 8 per group). Supplementation with lactoferrin during gestation and lactation prevented hypertension in adult offspring induced by a maternal adenine diet. The maternal adenine diet caused a decrease in the index of NO availability, which was restored by 67% with maternal LF supplementation. Additionally, LF was related to the regulation of the RAS, as evidenced by a reduced renal expression of renin and the angiotensin II type 1 receptor. Combined maternal adenine and LF diets altered beta diversity, shifted the offspring's gut microbiota, decreased propionate levels, and reduced the renal expression of SCFA receptors. The beneficial effects of lactoferrin are likely mediated through enhanced NO availability, rebalancing the RAS, and alterations in gut microbiota composition and SCFAs. Our findings suggest that maternal lactoferrin supplementation improves hypertension in offspring in a model of adenine-induced CKD, bringing us closer to potentially translating lactoferrin supplementation clinically for children born to mothers with CKD. [ABSTRACT FROM AUTHOR]

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]

Introduction: Prior to the introduction of novel food ingredients into the food supply, safety risk assessments are required, and numerous prediction models have been developed and validated to evaluate safety. Methods: The allergenic risk potential of Helaina recombinant human lactoferrin (rhLF, Effera™), produced in Komagataella phaffii (K. phaffii) was assessed by literature search, bioinformatics sequence comparisons to known allergens, glycan allergenicity assessment, and a simulated pepsin digestion model. Results: The literature search identified no allergenic risk for Helaina rhLF, K. phaffii, or its glycans. Bioinformatics search strategies showed no significant risk for cross-reactivity or allergenicity between rhLF or the 36 residual host proteins and known human allergens. Helaina rhLF was also rapidly digested in simulated gastric fluid and its digestibility profile was comparable to human milk lactoferrin (hmLF), further demonstrating a low allergenic risk and similarity to the hmLF protein. Conclusion: Collectively, these results demonstrate a low allergenic risk potential of Helaina rhLF and do not indicate the need for further clinical testing or serum IgE binding to evaluate Helaina rhLF for risk of food allergy prior to introduction into the food supply. [ABSTRACT FROM AUTHOR]

The poor thermal stability of lactoferrin (LF) hinders its bioavailability and use in commercial food products. To preserve LF from thermal denaturation, complexation with other biopolymers has been studied. Here we present the complex formation conditions, structural stability, and functional protection of LF by α‐lactalbumin (α‐LA). The formation of the LF–α‐LA complexes was dependent on pH, mass ratio, and ionic strength. Changing the formation conditions and cross‐linking by transglutaminase impacted the turbidity, particle size, and zeta‐potential of the resulting complexes. Electrophoresis, Fourier‐transform infrared spectroscopy, and circular dichroism measurements suggest that the secondary structure of LF in the LF–α‐LA complex was maintained after complexation and subsequent thermal treatments. At pH 7, the LF–α‐LA complex protected LF from thermal aggregation and denaturation, and the LF retained its functional and structural properties, including antibacterial capacity of LF after thermal treatments. The improved thermal stability and functional properties of LF in the LF–α‐LA complex are of interest to the food industry. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Lactoferrin is widely found in milk and has the ability to bind iron. Previous studies have reported that lactoferrin was effective in the prevention and treatment of acute alcohol-induced liver injury (AALI). Ferroptosis is a recently discovered cell death and is involved in the development of AALI. However, the potential role of lactoferrin in acute alcohol-induced ferroptosis is still unclear. In this study, we observed that lactoferrin (10, 20, and 40 μg/mL) significantly mitigated alcohol (300 m M)-induced injury in vitro. Additionally, lactoferrin (100 and 200 mg/kg BW) significantly alleviated alcohol (4.8 g/kg BW)-induced injury in vivo. Our results showed that lactoferrin inhibited alcohol-induced upregulation of the ferroptosis marker protein ACSL4 and downregulation of GPX4. Meanwhile, lactoferrin treatment successfully reversed the elevated malondialdehyde (MDA) levels and the reduced glutathione (GSH) levels caused by alcohol treatment. These results may indicate that lactoferrin significantly decreased ferroptosis in vivo and in vitro. Lactoferrin has the potential to chelate iron, and our results showed that lactoferrin (20 μg/mL) significantly reduced iron ions and the expression of the ferritin heavy chain (FTH) under FeCl 3 (100 μ M) treatment. It was demonstrated that lactoferrin had a significant iron-chelating effect and reduced iron overload caused by FeCl 3 in AML12 cells. Next, we examined iron content and the expression of iron metabolism marker proteins transferrin receptor (TFR), divalent metal transporter 1 (DMT1), FTH, and ferroportin (FPN). Our results showed that lactoferrin alleviated iron overload induced by acute alcohol. The expression of TFR and DMT1 was downregulated, and FPN and FTH were upregulated after lactoferrin treatment in vivo and in vitro. Above all, the study suggested that lactoferrin can alleviate AALI by mitigating acute alcohol-induced ferroptosis. Lactoferrin may offer new strategies for the prevention or treatment of AALI. [ABSTRACT FROM AUTHOR]

Since Coronavirus disease 2019 (COVID-19) still presents a considerable threat, it is beneficial to provide therapeutic supplements against it. In this respect, glycoprotein lactoferrin (LF) and lactoferricin (LFC), a natural bioactive peptide yielded upon digestion from the N-terminus of LF, are of utmost interest, since both have been shown to reduce infections of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for COVID-19, in particular via blockade of the virus priming and binding. Here, we, by means of biochemical and biophysical methods, reveal that LF directly binds to the S-protein of SARS-CoV-2. We determined thermodynamic and kinetic characteristics of the complex formation and mapped the mutual binding sites involved in this interaction, namely the N-terminal region of LF and the receptor-binding domain of the S-protein (RBD). These results may not only explain many of the observed protective effects of LF and LFC in SARS-CoV-2 infection but may also be instrumental in proposing potent and cost-effective supplemental tools in the management of COVID-19. [ABSTRACT FROM AUTHOR]

Autophagy is a new window of science that has been noticed due to the importance of specific therapies in cancer. In this study, the effect of lactoferrin (Lf) on the expression level of ATG101, mTOR and AMPK genes in breast cancer cell line MCF7, as well as the interaction between lactoferrin protein and their protein were investigated. The expression level of the genes was measured using a real-time PCR method. PDB, UniProt, KEGG, and STRING databases and ClusPro webserver and PyMol software were used in silico study. The results showed that the expression level of the ATG101 gene in treatment with concentrations of 100, 400, 600, and 800 μg/ml Lf decreased by 0.05, 0.13, 0.54 and 0.77, respectively. The expression level of the mTOR gene in treatment with concentrations of 100, 400, 600, and 800 μg/ml Lf decreased by 0.07, 0.05, 0.13, and 0.49 times respectively. The level of the AMPK gene expression in treatment with concentrations of 100, 400, 600, and 800 μg/ml Lf decreased by 0.05, 0.01, 0.06, and 0.03, respectively. Virtualization of the interaction of Lf protein with ATG101, mTOR and AMPK proteins by Pymol software showed that the N lobe region of Lf interacted with the HORMA domain of ATG101 protein, the fat domain of mTOR protein, and the CTD domain of AMPK protein. Although Lf was not able to increase the expression of autophagy-inducing genes, it may be able to induce autophagy through protein interaction by activating or inhibiting proteins related to autophagy regulation. • The autophagy regulation mechanism of lactoferrin is important in inhibiting cancer cells. • Lactoferrin can be used as a food and drug supplement for the prevention all cancers. • The study of interaction networks of proteins and genes is effective in drug design. • Docking studies have been developed to find unknown biological interactions that occur in the cell. [ABSTRACT FROM AUTHOR]

Mannheimia haemolytica is the main etiological bacterial agent in ruminant respiratory disease. M. haemolytica secretes leukotoxin, lipopolysaccharides, and proteases, which may be targeted to treat infections. We recently reported the purification and in vivo detection of a 110 kDa Zn metalloprotease with collagenase activity (110-Mh metalloprotease) in a sheep with mannheimiosis, and this protease may be an important virulence factor. Due to the increase in the number of multidrug-resistant strains of M. haemolytica, new alternatives to antibiotics are being explored; one option is lactoferrin (Lf), which is a multifunctional iron-binding glycoprotein from the innate immune system of mammals. Bovine apo-lactoferrin (apo-bLf) possesses many properties, and its bactericidal and bacteriostatic effects have been highlighted. The present study was conducted to investigate whether apo-bLf inhibits the secretion and proteolytic activity of the 110-Mh metalloprotease. This enzyme was purified and sublethal doses of apo-bLf were added to cultures of M. haemolytica or co-incubated with the 110-Mh metalloprotease. The collagenase activity was evaluated using zymography and azocoll assays. Our results showed that apo-bLf inhibited the secretion and activity of the 110-Mh metalloprotease. Molecular docking and overlay assays showed that apo-bLf bound near the active site of the 110-Mh metalloprotease, which affected its enzymatic activity. [ABSTRACT FROM AUTHOR]

Telogen effluvium is characterized by excessive hair shedding usually following a stressful event. Ferritin has been used in clinical practice as a biomarker of nonanemic iron deficiency in cases of telogen effluvium. During the years of the COVID19 pandemic, telogen effluvium was reported as a part of post covid manifestations. As ferritin was also a biomarker for inflammation in cases with covid infection, this study was designed to evaluate the value of ferritin in cases with postcovid telogen effluvium one hundred patients recovering from covid 19 for 4–12 weeks were included in the study, detailed drug and laboratory history was obtained and serum ferritin level was measured. the mean serum level of ferritin among telogen effluvium patients was significantly lower than controls (68.52 ± 126 and 137 ± 137.597 ug/L respectively). Patients with telogen effluvium used significantly more azithromycin and ivermectin and significantly less vitamin C, D, lactoferrin and zinc than the controls Although serum ferritin is lower among telogen effluvium patients, it was still higher than the cutoff value for diagnosing nonanemic iron deficiency, we suggest that it will not be a good biomarkers in these cases. Our secondary outcomes showed that dietary supplements used during active infection such as vitamin C, D, lactoferrin and zinc might have a preventive value on postcovid hair loss, while azithromycin and ivermectin could have a negative long term effect on telogen effluvium. [ABSTRACT FROM AUTHOR]

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

Background: A significant limitation of mucosal healing as a treatment target in Crohn’s disease is that Ileocolonoscopy remains the gold-standard for assessing disease activity. Identification of optimal biomarkers and their cut-off values is an unmet need in the context of tight monitoring strategy. Aim of work: To study the performance of Fecal lactoferrin in patients with Crohn’s disease in comparison to endoscopic assessment, clinical indices and fecal calprotectin to address whether it correlates with endoscopic severity of inflammation and whether it could be used as reliable surrogate marker of endoscopically detected mucosal healing after therapy. Methods: In this prospective study, 35 patients with active Crohn’s disease were recruited. All patients provided stool samples for lactoferrin and calprotectin at baseline and underwent colonoscopy. Twentysix (26) of these patients were followed up after 6-9 months of therapy initiation or upgrade. Fecal lactoferrin was compared with the simple endoscopic score of Crohn’s disease (SES-CD), Harvey-Bradshaw index (HBI) and fecal calprotectin. Data was then analyzed to identify cut-off levels to detect endoscopic response/remission. Results: Lactoferrin showed excellent performance in detecting remission (AUC 0.93) with a sensitivity of 85.7% and a specificity of 88.9% at a cut-off value of 21.5µg/g. A drop of more than 26.2% from baseline values is 100% sensitive and specific in detecting endoscopic response (≥50% reduction from baseline SES-CD). Lactoferrin showed a strong correlation with SES-CD (r=0.74) and calprotectin (r=0.91) Conclusion: Fecal lactoferrin is a reliable marker of response to therapy and mucosal healing, making endoscopic monitoring of treatment success less necessary. Whether lactoferrin is superior to calprotectin or not would require further investigation. [ABSTRACT FROM AUTHOR]

Objective: The increasing resistance of Malassezia yeasts against commonly used antifungal drugs dictates the need for novel antifungal compounds. Human lactoferrin-based peptides show a broad spectrum of antimicrobial activities. Various assays were performed to find the optimal growth conditions of the yeasts and to assess cell viability, using media with low lipid content to avoid peptide binding to medium components. Methods: In the current study, we tested the antimicrobial susceptibility of 30 strains of M. furfur that cover the known IGS1 genotypic variation. Results: hLF(1-11) inhibited the growth of all species tested, resulting in minimum inhibitory concentrations (MIC) values ranging from 12.5 to 100 μg/mL. In the combinatory tests, the majority of fractional inhibitory concentration indexes (FIC) for the tested strains of M. furfur were up to 1.0, showing that there is a synergistic or additive effect on the efficacy of the antifungal drugs when used in combination with hLF(1-11). Conclusion: Results showed that hLF(1-11) could be combined with fluconazole or amphotericin for the antimicrobial treatment of resistant strains, enhancing the potency of these antifungal drugs, resulting in an improved outcome for the patient. [ABSTRACT FROM AUTHOR]

Introduction: Avian coccidiosis presents a significant challenge to the poultry industry in Egypt, highlighting the urgent need for validating new drug targets offering promising prospects for the development of advanced anticoccidials. Although numerous reports highlight the activity of lactoferrin (LF) against various microorganisms, its potential against Eimeria has not been explored. The present study evaluated the potential anticoccidial effect of LF and diclazuril in broiler chickens experimentally infected with Eimeria tenella. Methods: A total of 100 one-day-old broiler chicks were divided into five equal groups (20 each) as follows: Group 1 (G1) served as the normal healthy control group, Group 2 (G2) consisted of chickens infected with 1 × 105 sporulated E. tenella oocysts at 14 days of age, Group 3 (G3) comprised infected chickens treated with diclazuril (0.5 mL/L in drinking water) for 3 days successively, Group 4 (G4) included infected chickens treated with LF (at a dose of 250 mg/kg of diet) from one day of age until the end of the study, and Group 5 (G5) comprised infected chickens treated with both LF and diclazuril. Results: The positive control group (G2) experienced significant reductions in body weight (BW), BW gain, serum glucose, lipase, amylase, total antioxidant capacity, several hematological indices, and total proteins, along with alterations in various antioxidant enzymes. Conversely, serum levels of aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatases (ALP), urea, creatinine, nitric oxide, mean corpuscular volume (MCV), White blood cells (WBCs), heterophils, alpha 2, beta 1, and liver contents of malondialdehyde were elevated in this group. Moreover, higher oocyst counts and lesion scores, along with histopathological alterations, were observed in G2. Remarkably, treatment with diclazuril and/or LF demonstrated potent antioxidant and anticoccidial effects, resulting in reduced shedding of oocysts, lesion scores, and lymphocytic infiltrates in the cecum. Additionally, these treatments improved the antioxidant and immune systems in chickens and restored all histopathological changes reported in the infected non-treated group (G2). Conclusion: This study offers novel perspectives on the potential anticoccidial effects of the combination of LF and diclazuril in broiler chickens infected with E. tenella, highlighting the potential synergistic actions of LF in treating poultry coccidiosis. [ABSTRACT FROM AUTHOR]

AbstractOvotransferrin(OVT)is a protein found in many types of egg white and has a wide range of functional properties. It has 50% homology with human/bovine lactoferrin, and is expected to be one of the most important alternative proteins for use in food and nutritional applications. This paper mainly reviews the structural characteristics and chemical properties of OVT, as well as its extraction and purification methods. It also systematically describes the various biological activities of OVT and its applications in food and medical industries. The challenges and limitations in the research of OVT were suggested. This review recommends some possible methods such as nanoparticle carriers and microencapsulation to improve the bioavailability and stability of OVT. In addition, this review highlights several strategies to overcome the limitations of OVT in terms of preparation and purification. This review systematically summarizes the recent advances in OVT and will provide guidance for the its development for food and nutritional applications. [ABSTRACT FROM AUTHOR]

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Background: Postmenopausal dyspareunia and vulvar pain are common complaints, affecting about 60% of women within a few years after hormone levels begin to decline (such as estrogen and androgen). Atrophic changes mainly located in the vulvar vestibule and vulnerability to vulvovaginal infections in postmenopause could be predisposing factors to the development of vulvar burning/pain and introital dyspareunia (vestibulodynia secondary to atrophy). Tibolone is the most effective and safe alternative for treating menopausal symptoms. The role of Lactobacilli and lactoferrin shows its effectiveness in the treatment of vaginal microbiota dysbiosis. The aim of the present study was to assess the efficacy of the combination of tibolone and an oral-specific Lactobacilli mixture in combination with bovine lactoferrin as synergistic therapy for the treatment of vestibulodynia related to atrophy. Methods: In this study, we included 35 postmenopausal women with at least 1 year of amenorrhea, affected by vulvar burning/pain and introital dyspareunia. All participants received treatment with open-label, oral Tibolone 2.5 mg and Lactobacilli mixture (5 × 109 CFU per capsule) in combination with bovine lactoferrin (Respecta®). Each product was taken once daily for 90 days. Results: After 90 d of therapy with TIB+ Respecta®, in 30 women that completed the treatment, there was a statistically significant decrease from the baseline in the mean of the Visual Analog Scale for vulvar burning/pain and a reduction in scores in the pain evaluation test. Conclusions: This study provides evidence that the combination of TIB+ Respecta® was effective in reducing symptoms related to vestibular pain and hypersensitivity in a postmenopausal setting. [ABSTRACT FROM AUTHOR]

N-Glycosidase (PNGase) is a type of glycoside hydrolase whose main function is to release N-glycan chains from glycopeptides or glycoproteins, holding significant application value in fields such as food and biomedicine. Currently, commercial PNGases exhibit certain limitations in their application. Therefore, developing new PNGases with superior performance holds research value. This study successfully obtained a novel PNGase, named PNGase Dc, by expressing the gene encoding PNGase from Dyella caseinilytica in Escherichia coli. The molecular weight of PNGasse Dc was 63.01 kDa. Its enzymatic characteristics, functionality, and potential applications were then analyzed. The enzymatic characterization results indicated that the optimal pH and temperature for PNGase Dc are 2.0 and 37 °C, respectively, and its catalytic reaction did not depend on metal ions.The enzyme also demonstrated excellent stability, retaining its activity even after storage at 4 °C for 45 days. Molecular docking analysis indicated that PNGase Dc interacts with its substrate N'N-diacetylchitobiose through hydrogen bonds and van der Waals forces. Site-directed mutagenesis identified Asp102 and Glu236 as key amino acids affecting the enzyme's activity.PNGase Dc exhibited effective deglycosylation on standard glycoproteins, including horseradish peroxidase and lactoferrin. Lastly, PNGase Dc's application potential was evaluated.Arabidopsis thaliana and mouse plasma was used as substrates, confirming its promising applicability in the study of glycoproteins from both animal and plant sources.In summary, this research introduced a new enzymatic tool, PNGase Dc, for the study of glycoproteins derived from animal and plant sources, thereby laying a theoretical foundation for the enzyme's development and utilization. [ABSTRACT FROM AUTHOR]

This work presents a thorough characterization of Helaina recombinant human lactoferrin (rhLF, Effera™) expressed in a yeast system at an industrial scale for the first time. Proteomic analysis confirmed that its amino acid sequence is identical to that of native human LF. N-linked glycans were detected at three known glycosylation sites, namely, Asparagines-156, -497, and -642 and they were predominantly oligomannose structures having five to nine mannoses. Helaina rhLF's protein secondary structure was nearly identical to that of human milk lactoferrin (hmLF), as revealed by microfluidic modulation spectroscopy. Results of small-angle X-ray scattering (SAXS) and analytical ultracentrifugation analyses confirmed that, like hmLF, Helaina rhLF displayed well-folded globular structures in solution. Reconstructed solvent envelopes of Helaina rhLF, obtained through the SAXS analysis, demonstrated a remarkable fit with the reported crystalline structure of iron-bound native hmLF. Differential scanning calorimetry investigations into the thermal stability of Helaina rhLF revealed two distinct denaturation temperatures at 68.7 ± 0.9 °C and 91.9 ± 0.5 °C, consistently mirroring denaturation temperatures observed for apo- and holo-hmLF. Overall, Helaina rhLF differed from hmLF in the N-glycans they possessed; nevertheless, the characterization results affirmed that Helaina rhLF was of high purity and exhibited globular structures closely akin to that of hmLF. [ABSTRACT FROM AUTHOR]

Noncovalent interactions of 4 selected phenolic acids, including gallic acid (GA), caffeic acid (CA), chlorogenic acid (CGA), and rosmarinic acid (RA) with lactoferrin (LF) were investigated. Compound combined with LF in the binding constant of CA > GA > RA > CGA, driven by van der Waals and hydrogen bonding for GA, and hydrophobic forces for others. Conformation of LF was affected at secondary and ternary structure levels. Molecular docking indicated that GA and CA located in the same site near the iron of the C-lobe, whereas RA and CGA bound to the C2 and N-lobe, respectively. Significantly enhanced antioxidant activity of complexes was found compared with pure LF, as demonstrated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis(2-ethylbenzothiazoline-6-sulfonate) (ABTS), and ferric reducing antioxidant power (FRAP) models. Caffeic acid, CGA, and RA significantly decreased the emulsifying stability index and improved foam ability of LF, and the effect of CA and RA was the most remarkable, respectively. [Display omitted] [ABSTRACT FROM AUTHOR]

The effect of gravitational unloading (antiorthostatic hindlimb suspension) and subsequent recovery on the mineral density and mechanical properties of the femoral and tibial bones in Wistar rats was studied during oral administration of a human lactoferrin (LF) biotechnological analog (200 mg/kg) derived from the milk of producer goats. Bone mineral density was determined by dual energy X-ray absorptiometry, while bone strength and stiffness were assessed via the three-point bending test. It was shown that 21-day gravitational unloading led to a decrease in the mineral density of the tibia and femur. Oral LF administration had no significant effect on the mineral density and projected area of the bones. There were no statistically significant differences in mechanical stiffness between the experimental groups, although after readaptation, the ultimate strength was significantly higher in LF-administered groups. Thus, the results may indicate the potential of LF preparations as prophylactic agents for maintaining bone strength. At the same time, the maintaining of bone mineral density under deficit-stimulating conditions requires a consideration of alternative dosages and drug delivery methods. [ABSTRACT FROM AUTHOR]

Lactoferrin is an antimicrobial glycoprotein that demonstrates a broad-spectrum of activity against a wide variety of clinical pathogens. This study investigated the potential of bovine lactoferrin (bLf) against multidrug resistant Staphylococcus capitis (S. capitis) strains. Growth curve analysis and time-kill curves demonstrated that at 750 µg ml−1 lactoferrin significantly inhibited (50.6%, P < 0.05) the growth of most isolates tested (90%), and this effect was based on a bacteriostatic mechanism. At the same concentration, bLf also significantly inhibited (30%, P < 0.05) biofilm formation in 40% of strains tested. Combinations of bLf with selected antibiotics were assessed for enhanced antimicrobial activity using growth curves. BLf combined with β-lactam antibiotics reduced the growth of S. capitis strains, however, the effects were not significant. BLf displays antimicrobial effects against multidrug resistant S. capitis isolates, but with strain-specific effects. [ABSTRACT FROM AUTHOR]