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Obesity is a global epidemic, it can induce glucose and lipid metabolism disorder and non-alcoholic fatty liver disease (NAFLD). This study explored a new way to control weight and improve fatty liver, namely, living in hypoxia environment and supplement with lactoferrin (Lf). Sixty male C57BL/6J mice were divided into six groups, namely, control, hypoxia, high-fat diet, hypoxia + high-fat diet, hypoxia + high-fat diet + low dose Lf intervention, and hypoxia + high-fat diet + high-dose Lf intervention. Mice in the hypoxia treatment groups were treated with approximately 11.5 % oxygen for 6 h every day for 8 weeks. Results showed that interventions combining Lf and hypoxia treatments showed better effect against obesity and NAFLD than hypoxia treatment alone. The interventions controlled weight gain in mice, improved glucolipid metabolism in mice. The combination intervention reduced cholesterol absorption by reducing the level of hydrophobic bile acids, and elevating the level of hydrophilic bile acids. Gut microbiota analysis revealed that the combination intervention considerably elevated short chain fatty acids (SCFAs)-producing bacteria level, and reduced the Desulfovibrionaceae_unclassified level. Thus, Lf combined with hypoxia intervention effectively prevents obesity and NAFLD by restoring gut microbiota composition and bile acid profile. [ABSTRACT FROM AUTHOR]

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

Multiple sclerosis is a chronic inflammatory demyelinating disorder of the CNS characterized by continuous myelin damage accompanied by deterioration in functions. Clobetasol propionate (CP) is the most potent topical corticosteroid with serious side effects related to systemic absorption. Previous studies introduced CP for remyelination without considering systemic toxicity. This work aimed at fabrication and optimization of double coated nano-oleosomes loaded with CP to achieve brain targeting through intranasal administration. The optimized formulation was coated with lactoferrin and chitosan for the first time. The obtained double-coated oleosomes had particle size (220.07 ± 0.77 nm), zeta potential (+30.23 ± 0.41 mV) along with antioxidant capacity 9.8 μM ascorbic acid equivalents. Double coating was well visualized by TEM and significantly decreased drug release. Three different doses of CP were assessed in-vivo using cuprizone-induced demyelination in C57Bl/6 mice. Neurobehavioral tests revealed improvement in motor and cognitive functions of mice in a dose-dependent manner. Histopathological examination of the brain showed about 2.3 folds increase in corpus callosum thickness in 0.3 mg/kg CP dose. Moreover, the measured biomarkers highlighted the significant antioxidant and anti-inflammatory capacity of the formulation. In conclusion, the elaborated biopolymer-integrating nanocarrier succeeded in remyelination with 6.6 folds reduction in CP dose compared to previous studies. • Remyelination is a promising tactic to restore lost function in multiple sclerosis. • Lactoferrin, chitosan-coated oleosomes was optimized and loaded with Clobetasol. • Histometric evaluation confirmed increased myelin density after 10 days treatment. • The formulation displayed a significant antioxidant and anti-inflammatory role. [ABSTRACT FROM AUTHOR]

The milk-derived bovine lactoferrin (bLf) is an iron-binding glycoprotein with remarkable selective anticancer activity towards highly metastatic cancer cells displaying the proton pump V-ATPase at the plasma membrane. As studies aiming to dissect the bLf mechanisms of action are critical to improve its efficacy and boost its targeted clinical use, herein we sought to further uncover the molecular basis of bLf anticancer activity. We showed that bLf co-localizes with V-ATPase and cholesterol-rich lipid rafts at the plasma membrane of highly metastatic cancer cells. Our data also revealed that bLf perturbs cellular trafficking, induces intracellular accumulation of cholesterol and lipid rafts disruption, downregulates PI3K, and AKT or p-AKT and inhibits glycolysis of cancer cells harbouring V-ATPase at the plasma membrane lipid rafts. Altogether, our results can lay the foundation for future bLf-based targeted anticancer strategies as they unravel a novel cascade of molecular events that explains and further reinforces bLf selectivity for cancer cells displaying plasmalemmal V-ATPase. • Lactoferrin perturbs intracellular trafficking and inhibits glycolysis. • Lactoferrin disrupts cholesterol-rich lipid rafts of highly metastatic cancer cells. • A novel cascade of molecular events triggered by lactoferrin in cancer cells was unveiled. [ABSTRACT FROM AUTHOR]

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

This study identifies promising potential of a novel and safer nanocombination of bovine milk lactoperoxidase (LPO) and lactoferrin (LF) to target breast cancer in vitro and in adult female albino rat model. Favorable selective anticancer effects of the prepared nanocombination were observed, in a dose-dependent manner, against both MCF-7 and MDA cell lines, sparing normal HFB-4 cells. The administration of LPO + LFNPs markedly improved the induced-breast cancer disorders, prolonged survival and reduced the values of serum TNF-α, IL1β, CD4+, ALAT, ASAT, urea, creatinine, cholesterol and triglycerides with remarkable elevation in mammary SOD and GPx activity and GSH level. Moreover, the histopathological findings showed that LPO + LFNPs succeeded in prevention of mammary gland tumorigenesis. Superior efficacy of LPO + LFNPs was observed against pro-inflammatory cytokines through their anti-inflammatory and immunomodulatory properties. The treatment of LPO + LFNPs more significantly modulated the apoptosis and enhanced the expression of cell cycle regulator genes, which demonstrates a successful tumor therapy in vitro and in vivo. Therefore, this study provided evidence that the chemo-preventive feature of LPO + LFNPs may offer a novel alternative therapy for the treatment of breast cancer through enhances apoptosis pathway, improvement of immune response, reduction of inflammation and restoration of the impaired oxidative stress. [ABSTRACT FROM AUTHOR]

Protein-polysaccharide combinations frequently demonstrate functional attributes that surpass those of the individual biopolymers. This study aimed to elucidate the physicochemical, structural, and functional properties of two types of lactoferrin (LF)-carboxymethyl chitosan (CMCS) complexes formed by physical mixing and enzymatic glycosylation. LF and CMCS interactions were characterized using phase behavior, particle size, and zeta-potential analysis. The results indicated the formation of an electrostatic complex with a size of <150 nm at pH 8. SDS-PAGE and Fourier transform infrared spectroscopy confirmed that TGase catalyzed the cross-linking and glycosylation of LF, with the extent of glycosylation dependent on the concentration of CMCS. The introduction of CMCS has been observed to result in alterations to the secondary, tertiary, and microstructure of LF, which impact the functional characteristics of LF. The incorporation of CMCS markedly enhances the thermal stability of LF, with a denaturation temperature of 126.66 °C. The addition of CMCS (0.5 wt%) to LF resulted in a significant (P < 0.05) improvement in the emulsifying activity of LF, but it did not improve its foaming properties. This study offers novel ideas and approaches for developing protein and polysaccharide complexes with improved functional properties, thereby expanding the potential applications of edible proteins., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare regarding this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There is fast increasing interest in the development of alimentary protein stabilized emulsions due to their potential applications in functional food fields. This work studied the effect of glycation degree with chitosan oligosaccharide (COS) on the emulsifying properties of lactoferrin (LF) through Maillard reaction. In the present study, SDS-PAGE and FT-IR were used to confirm LF and COS covalently binding together successfully. Intrinsic fluorescence showed that glycation with COS led more hydrophobic groups exposed to the surface of the structure and particle size increase of LF. Emulsions with 50% (v /v) oil phase and protein concentration of 2% (w / v) was fabricated through one-step shear method. Compared with native LF, emulsions stabilized by LF-COS conjugates showed smaller droplet size and lower creaming index (CI). Among these samples, LF-COS conjugates under 4 h had the best emulsifying efficiency and stability, the emulsion droplet size and the CI of which decreased 39.66% and 28.55% compared with LF, respectively. Furthermore, glycation with COS enhanced the interfacial activity of LF leading to more adsorbing amount and forming thicker layer on the droplets and gel network in the emulsions. This finding would make sense to further understand the modification of emulsifying properties of alimentary proteins through glycosylation with saccharides and develop novel protein-based emulsifiers. [ABSTRACT FROM AUTHOR]

Lactoferrin (LAC) is an iron-binding glycoprotein found in mammalian secretion, such as milk and colostrum, which has several advantageous biological characteristics, such as antioxidant and antimicrobial activity, intestinal iron absorption and regulation, growth factor activity, and immune response. LAC is an active GRAS food ingredient and can be included in the food packaging/film matrix in both free and encapsulated forms to increase the microbial, mechanical, barrier, and thermal properties of biopolymer films. Additionally, LAC-containing films maintain the quality of fresh food and extend the shelf life of food products. This paper primarily focuses on examining how LAC affects the antimicrobial, antioxidant, physical, mechanical, thermal, and optical properties of packaging films. Moreover, the paper explains the attributes of films incorporating LAC within different matrices, exploring the interaction between LAC and polymers. The potential of LAC-enhanced food packaging technologies is highlighted, showcasing their promising applications in sustainable food packaging. [Display omitted] [ABSTRACT FROM AUTHOR]

Complexes of polysaccharides and proteins have superior physicochemical and functional properties compared to single proteins or polysaccharides. In this study, lactoferrin-hyaluronic acid (LF-HA) complexes were prepared by both ultrasonic and thermal treatment. Appropriate preparation conditions, including ultrasonic and thermal treatment conditions, have been established. The complexes formed by different methods were structurally characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis, fourier transform infrared spectroscopy, and circular dichroism spectroscopy. Ultrasound formed non-covalent binding, while thermal treatment generated covalent bonding, altering the structure of LF. The LF-HA complexes showed improved heat stability, foaming stability, emulsifying activity and antioxidant capacity, but deceased foaming ability. Iron binding ability could only be improved by HA through thermal treatment. Moreover, the in vitro digestibility of LF-HA complexes decreased to below 80 % compared to LF. [Display omitted] • Ultrasound caused non-covalent binding while heat formed covalent binding in LF-HA. • The formation of LF-HA complexes altered LF structure, and hindered its digestion. • LF-HA had better thermal stability, emulsifying activity and antioxidant properties. • LF-HA complex formed by heat showed higher iron-binding ability. [ABSTRACT FROM AUTHOR]

Novel amphiphilic nanoconjugates of hyaluronic acid (HA), 50 kDa (HA 50) and 100 kDa (HA 100), and the lipopeptide biosurfactant surfactin (SF) were developed for potential anticancer applications. Physicochemical characterization indicated the formation of an ester conjugate (HA: SF molar ratio 1: 40) with the HA 50 -SF derivative exhibiting higher degree of substitution, hydrolytic stability, and surface activity. Self-assembly resulted in nanomicelles with smaller size and greater negative charge relative to SF micelles. Biological data demonstrated distinct anticancer activity of HA 50 -SF which displayed greater synergistic cytotoxicity and selectivity for MDA-MB 231 and MCF-7 breast cancer cells alongside greater modulation of apoptosis-related biomarkers leading to apoptosis. As bioactive vector for chemotherapeutic agents, the selected HA 50 -SF nanoconjugate efficiently (70 %) entrapped berberine (BER) producing a sustained release BER-HA 50 -SF synergistic anticancer nanoformulation. Lactoferrin (Lf) coating for dual HA/Lf targeting endowed Lf/BER-HA 50 -SF with significantly greater selectivity for both cell lines. A murine Ehrlich breast cancer model provided evidence for the efficacy and safety of Lf/BER-HA 50 -SF via tumoral, histological, immunohistochemical, molecular and systemic toxicity assessments. Thus, HA-SF nanoconjugates integrating the HA and SF properties and biofunctionalties present a novel biopolymer-biosurfactant platform of benefit to oncology nanomedicine and possibly other applications. [Display omitted] • Hyaluronic acid-anticancer surfactin conjugate shows new functionalities • Amphiphilized hyaluronic acid self-assembles into targeted anticancer nanomicelles • Hyaluronated surfactin shows enhanced surface activity and cancer cell selectivity • Conjugate is promising as bioactive agent and nanocarrier against breast cancer • Hyaluronic acid-biosurfactant conjugates provide a versatile anticancer platform [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf) is a versatile natural milk-derived protein that exhibits multiple interesting biological activities. Since it is safe for human administration and currently manufactured using low cost and well-established large-scale processes, the Lf scientific community has been devoted at dissecting its mechanisms of action towards its more rational and efficient use for various applications. Emerging literature has identified proton pumping ATPases as molecular targets of Lf in different cellular models linked to distinct activities of this natural protein. Information on this subject has not been systematically analysed before, hence herein we review the current state of art on the effect of Lf on proton pumping ATPases. Though structurally different, we propose that Lf holds a proton pump inhibitor (PPI)-like activity based on the functional resemblance with the classical inhibitors of the stomach H+/K+-ATPase. The downstream events and outcomes of the PPI-like activity of Lf, as well as its impact for the development of improved Lf applications are also discussed. • Lactoferrin inhibits bacterial F-ATPase contributing to its antimicrobial activity. • Lactoferrin hinders both Pma1p and V-ATPase of yeast cells deregulating pH. • Lactoferrin selectively impairs V-ATPase activity of highly metastatic cancer cells. • Repurposing of proton pump inhibitors towards anticancer therapy is promising. • Lactoferrin exhibits proton pump inhibitor-like activity. [ABSTRACT FROM AUTHOR]

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

Carboxymethyl chitosan (CMCS)-based complex coacervate has attracted much attention in drug oral delivery due to its pH-responsive property. As a unique ampholyte polymer, the self-coacervation of CMCS has great research potential. In this work, CMCS self-coacervates were prepared by adjusting the pH of the CMCS aqueous solution close to its isoelectric point. The Fourier-transformed infrared spectroscopy (FTIR) results revealed that electrostatic interactions, hydrogen bonding, and hydrophobic interactions were involved in the self-coacervation of CMCS. The obtained self-coacervates presented a dense surface structure, and were stable at a wide pH range of 3.0–6.0, and gradually dissolved under basic conditions. Although self-coacervation decreased the crystallinity and thermal stability of CMCS, the obtained coacervates showed excellent pH-responsive properties and ionic strength stability. We also investigated its potential in lactoferrin (LF) encapsulation and oral delivery. The CMCS self-coacervates exhibited a high encapsulation efficiency (EE) of 94.79 ± 0.49% and loading capacity (LC) of 26.29 ± 0.52% when the addition amount of LF was 2 mg. The simulated gastric digestion results demonstrated that CMCS self-coacervates could protect more than 80% of LF from hydrolysis and maintain the bioactivities of LF. Accordingly, the self-coacervation of CMCS could be used as a pH-responsive encapsulation and delivery strategy. [ABSTRACT FROM AUTHOR]

The formation of complexes may be used for the development of delivery systems in foods field. The aim of this study was to explore the interaction mechanism between Lentinus edodes mycelia polysaccharide (LMP) and bovine lactoferrin (BLF), and the activity of LMP-BLF complex to inhibit oxidative stress in islet β cells. The interaction mechanisms of LMP with BLF were investigated with multi-spectroscopic techniques. The multi-spectroscopic analysis result showed that LMP bound with BLF by van der Waals force and hydrogen bond. The quenching mechanism of BLF with LMP was static quenching. Cell viability, reactive oxygen species (ROS) level, apoptosis and the related signaling pathways were detected with thiazolyl blue tetrazolium bromide (MTT) assay, 2,7-Dichlorofluorescin diacetate (DCFH-DA) staining, Hoechst 33258 staining and Western blot methods respectively. The complex alleviated apoptosis induced by hydrogen peroxide (H 2 O 2), and inhibited oxidative stress via MAPK pathways in MIN6 cells. In addition, the complex was able to promote glucose uptake in HepG2 cells. These results will broaden our understanding of LMP-BLF complexes and the applications of polysaccharide-protein complexes in the foods field. The complex of Lentinus edodes mycelia polysaccharide (LMP) and bovine lactoferrin (BLF) alleviated H 2 O 2 -induced oxidative stress in MIN6 cells by inhibiting the MAPK signaling pathways. In addition, it could reverse insulin resistance in HepG2 cells. [Display omitted] • Lentinus edodes mycelia polysaccharide formed stable complexes with bovine lactoferrin. • The main binding forces of the complex were hydrogen bond and van der Waals forces. • The LMP-BLF complex could inhibit oxidative stress in islet β cells. • Inhibitory effect was involved in the inhibiting of MAPK signaling pathways. • The complex reversed insulin resistance in HepG2. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) has attracted great attention due to its various bioactivities, which depend on the degree of saturation with different cations. This study focused on the synergistic effect of LF and Zn2+ on human gingival fibroblasts (hGFs), considering antioxidant activities, cell proliferation, and collagen gene expression levels in these cells to improve the wound healing. The hGFs were cultured in an experimental medium, containing 1000 μg/mL of LF and various concentrations of ZnCl 2. The cells were subjected to oxidative damage by exposure to 600 μM H 2 O 2 for 30 min before incubation in the experimental medium. The cell proliferation rate and the relative gene expression levels of genes associated with apoptosis, antioxidant enzymes, and collagen were compared. H 2 O 2 decomposition by LF was also measured using a colorimetric assay. LF enhanced hGF proliferation and the expression of collagen. Furthermore, LF directly scavenged H 2 O 2 and prevented lipid peroxidation by enhancing the expression of glutathione peroxidase 4 gene expression, resulting in the prevention of apoptosis and recovery of the cells from H 2 O 2 -induced oxidative damage. The addition of ZnCl 2 enhanced these results. The results indicated that LF with Zn-ion could play an important role in modulating the functions related to wound healing. [ABSTRACT FROM AUTHOR]

In the present work, lactoferrin (Lf) based nanoparticle incorporated self-supporting gel encapsulating a flavonoid, quercetin (Q), was developed. The complex formation between Lf and Q was assessed using molecular docking and dynamics simulation that lactoferrin and quercetin showed strong interaction and binding supporting hydrophobic interaction. The microscopic, spectroscopic, and x-ray techniques were used to characterize the gel extensively. In vitro drug release was studied to understand the release pattern of quercetin from the protein gel. The viscosity of the gel and its rheological characteristics were determined using a Brookfield viscometer. Ex vivo skin permeation studies using vertical diffusion cells were carried out to understand its skin permeation properties. The gel showed strong anti-oxidant activity using the DPPH scavenging assay. The enhanced effect of the Lf-Q complex on antioxidant enzyme activity (superoxide dismutase, catalase, and malondialdehyde), was supported by molecular dynamics, surface hydrophobicity, and in vitro studies. To investigate the effect of the gel on angiogenesis, the chorioallantoic membrane assay was performed and its compatibility with erythrocytes was also assessed. Suitability for topical administration was assessed using skin irritation studies performed on Sprague Dawley rats. The overall results suggest that the developed NiPG is suitable for cutaneous localization of quercetin with enhanced antioxidant activity. • Development of quercetin-Lactoferrin complex based self-supporting Gel • Nanoparticle incorporated protein gel (NiPG) for delivery of polyphenols • Exploring interaction between quercetin-Lactoferrin • Enhanced antioxidant enzyme activity based on enhanced hydrophobicity of Quercetin. [ABSTRACT FROM AUTHOR]

Mucormycosis is a deadly infection which is caused by fungi of the order Mucorales including species belonging to the genus Rhizopus , Mucor , Mycocladus , Rhizomucor , Cunninghamella , and Apophysomyces. Despite antifungal therapy and surgical procedures, the mortality rate of this disease is about 90-100% which is exceptionally high. The hypersensitivity of patients with raised available serum iron indicates that the Mucorales are able to use host iron as a critical factor of virulence. This is because iron happens to be a crucial element playing its role in the growth of cells and development. In this review, we have described Lactoferrin (Lf) as a potential iron-chelator. Lf is a naturally occurring glycoprotein which is expressed in most of the biological fluids. Moreover, Lf possesses exclusive anti-inflammatory effects along with several anti-fungal effects that could prove to be helpful to the pathological physiology of inexorable mucormycosis cases. This literature summarises the biological insights into the Lf being considered as a potential fungistatic agent and an immune regulator. The review also proposes that unique potential of Lf as an iron-chelator can be exploited as the adjunct treatment for mucormycosis infection. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) belongs to the family of transferrins having multifunctional roles associated with the immune system of animals. To follow the aims for this study was selected 20 sequences of LF from mammalian species to evaluate the chemical, biological, and structural properties. Bioinformatics approaches used programs such as MAFFT for sequence alignment; PartitionFinder and MrBayes for phylogenetic approaches; I-TASSER, PROCHECK, Molecular Operating Environment (MOE), SWISS Model server, Peptide DB and Expasy ProtParam to estimate the physicochemical properties, to model the protein and predicted secondary structures. A phylogenic analysis shows species with genetic similarities clustered by complexity and unique grouping between Capra hircus , Macaca mulatta , and Myotis lucifugus , since they presented more amino acids but not overall changes in the iron-binding sites or biological aspects. Structural deviations in these clusters obtained in LF from those species were found in residues 46 (position 406-450), that is part of alpha-helix, and 37 (position 295-331), that is part of the beta-sheets. Our predicted model can be used to investigate more about structural aspects of LF and be applied for medicinal research. • The clades of amino acids from 20 mammals presented higher amount of ALA and LEU. • The predicted secondary structure indicated a higher percentage of alpha helix. • An insertion of 46 AA was observed in the protein from Capra hircus data. • The biological aspects of the protein are conserved. • This paper contributes with research data and industrial power for lactoferrin. [ABSTRACT FROM AUTHOR]

Understanding nonionic surfactant-protein interactions is fundamental from both technological and scientific points of view. However, there is a complete absence of kinetic data for such interactions. We employed surface plasmon resonance (SPR) to determine the kinetic and thermodynamic parameters of bovine lactoferrin-Brij58 interactions at various temperatures under physiological conditions (pH 7.4). The adsorption process was accelerated with increasing temperature, while the desorption rate decreased, resulting in a more thermodynamically stable complex. The kinetic energetic parameters obtained for the formation of the activated complex, [bLF-Brij58]‡, indicated that the potential energy barrier for [bLF-Brij58]‡ formation arises primarily from the reduction in system entropy. [bLF-Brij58]○ formation was entropically driven, indicating that hydrophobic interactions play a fundamental role in bLF interactions with Brij58. [Display omitted] • Lactoferrin-Brij58 interaction form a entropically driven complex, [bLF-Brij58]○. • Stability of [bLF-Brij58]○ increases at elevated temperatures. • [bLF-Brij58]○ is formed via the transition state intermediate [bLF-Brij58]‡. • [bLF-Brij58]‡.enthalpic barrier is higher in the adsorption step. • Transition state entropic barrier is dominated by conformation change. [ABSTRACT FROM AUTHOR]

Thermal stability and iron saturation of lactoferrin (LF) are of great significance not only for the evaluation of the biological activities of LF but also for the optimization of the isolation and drying process parameters. Differential scanning calorimetry (DSC) is a well-established and efficient method for thermal stability and iron saturation detection in LF. However, multiple DSC measurements are typically performed sequentially, thus time-consuming and low throughput. Herein, we introduced the differential scanning fluorimetry (DSF) approach to overcome such limitations. The DSF can monitor LF thermal unfolding with a commonly available real-time PCR instrument and a fluorescent dye (SYPRO orange or Glomelt), and the measured melting temperature of LF is consistent with that determined by DSC. On the basis of that, a new quantification method was established for determination of iron saturation levels using the linear correlation of the degree of ion saturation of LF with DSF measurements. Such DSF method is simple, inexpensive, rapid (<15 min), and high throughput (>96 samples per experiment), and provides a valuable alternative tool for thermal stability detection of LF and other whey proteins. [Display omitted] [ABSTRACT FROM AUTHOR]

Two chia mucilages with different viscosities, obtained by extraction conditions optimized in a previous work, were homogenized by high pressure homogenization (HPH). Particle size, molecular weight, zeta potential, FTIR spectrum, rheological properties, water absorption capacity, water holding capacity and iron binding capacity were determined on both mucilages treated and without treatment. Homogenization led to a significant reduction in viscosity respect to chia mucilage controls, which can be related to the decrease in particle size and molecular weight. A high iron binding capacity was obtained for both mucilages. FTIR spectra of both mucilages with iron showed displacements in bands related with stretching of carboxylic uronic acids, suggesting the interaction site with this mineral. This interaction was also verified by particle size determination with a displacement to higher sizes in the presence of iron. Potential zeta showed a significant reduction in the presence of iron. A model to explain the binding between chia mucilage and iron is proposed. HPH appears as an alternative to expand chia mucilage functionality reducing the viscosity of chia mucilage solutions for the offer of a new ingredient also with optimal levels of hydration and iron binding capacity. [Display omitted] • Technological properties of chia mucilage (CM) were studied. • High pressure homogenization (HPH) modified the structure of CM. • HPH reduced particle size and viscosity of CM. • CM treated by HPH maintained optimal hydration and iron binding properties. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium with adaptive metabolic abilities. It can cause hospital-acquired infections with significant mortality rates, particularly in people with already existing medical conditions. Its ability to develop resistance to common antibiotics makes managing this type of infections very challenging. Furthermore, oxidative stress is a common consequence of bacterial infection and antibiotic therapy, due to formation of reactive oxygen species (ROS) during their mode of action. In this study we aimed to alleviate oxidative stress and enhance the antibacterial efficacy of ciprofloxacin (CPR) antibiotic by its co -encapsulation with naringin (NAR) within a polyelectrolyte complex (PEX). The PEX comprised of polycationic lactoferrin (LF) and polyanionic pectin (PEC). CPR/NAR-loaded PEX exhibited spherical shape with particle size of 237 ± 3.5 nm, negatively charged zeta potential (−23 ± 2.2 mV) and EE% of 61.2 ± 4.9 for CPR and 76.2 ± 3.4 % for NAR. The LF/PEC complex showed prolonged sequential release profile of CPR to limit bacterial expansion, followed by slow liberation of NAR, which mitigates excess ROS produced by CPR's mechanism of action without affecting its efficacy. Interestingly, this PEX demonstrated good hemocompatibility with no significant in vivo toxicity regarding hepatic and renal functions. In addition, infected mice administrated this nanoplatform intravenously exhibited significant CFU reduction in the lungs and kidneys, along with reduced immunoreactivity against myeloperoxidase. Moreover, this PEX was found to reduce the lungs´ oxidative stress via increasing both glutathione (GSH) and catalase (CAT) levels while lowering malondialdehyde (MDA). In conclusion, CPR/NAR-loaded PEX can offer a promising targeted lung delivery strategy while enhancing the therapeutic outcomes of CPR with reduced oxidative stress. [Display omitted] [ABSTRACT FROM AUTHOR]

In order to modify colonic release behavior of lactoferrin (Lf), a hydrophobic composite nanofibrous carrier (CNC) was constructed by emulsion coaxial electrospinning. Ethylcellulose/pectin based water-in-oil emulsion and Lf-contained polyvinyl alcohol solution were used as shell and core fluids, respectively. An electrospinning diagram was first constructed to screen out suitable viscosity (51–82 cP) and conductivity (960–1300 μS/cm) of the dispersed phase of pectin solution for successful electrospinning of shell emulsion. Varying mass fraction of pectin solution (5 %–20 %) of shell emulsion during emulsion coaxial electrospinning obtained CNCs with different micro-structures, labeled as 5&95 CNC, 10&90 CNC, 15&85 CNC, 20&80 CNC. These CNCs all achieved colonic delivery of Lf (>95 %), and the time for complete release of Lf in simulated colon fermentation process were 10, 7, 5 and 3 h, respectively. That is, the greater the pectin content in CNC, the faster the release rate of stabilized Lf in colon. Lf release in simulated colon fermentation fluid involved complex mechanisms, in which diffusion release of Lf was dominant. Increasing colonic release rate of Lf enhanced its regulation effect on the expression levels of cell cycle arrest and apoptosis-related protein and promote its effective inhibition on the proliferation of HCT116 cell. • Composite nanofibrous carrier (CNC) was fabricated by emulsion coaxial electrospinning. • CNC involved hydrophobic outer layer, ethylcellulose-pectin middle layer, and core of Lf. • CNC with various microstructure was obtained by varying mass fraction of pectin solution. • The greater the pectin content in CNC, the faster the release rate of stabilized Lf in colon. • Faster rate of Lf release generated higher anti-proliferation activity against HCT116 cells. [ABSTRACT FROM AUTHOR]

In the present study, we have developed the core-shell metal organic framework (MOF) of zinc, wherein titanocene dichloride (TC) loaded lactoferrin (Lf) functioned as a core. The complexation of TC to Lf was studies using molecular dynamics study, Quantum mechanical model and spectroscopic investigations. Plackett-Burman design was used to screen and select the critical factors affecting the responses (size, zeta potential and PDI) while the effect of those parameter on the quality attributes (size and yield) was studied by means of a Box-Behnken design. The optimised Lf-TC nanoparticles were loaded inside the ZIF-8 framework along with an anticancer agent 5 Fluorouracil and characterized using techniques like FTIR, PXRD, Raman spectroscopy, EDX and UV-NIR spectroscopy and morphological techniques like SEM, TEM, AFM. The compatibility of the loaded ZIF-8 framework was examined by haemocompatibility studies. The potential of developed nanoplatform against Neuroblastoma was assessed using a cell line studies along with in vivo toxicity studies to ascertain its safety for after in-vivo administration in Wistar rats. Therefore, we can conclude that by employing the approach of DOE we were able to optimize the size and yield of Lf-TC NPs and further by loading inside ZIF-8 framework along with an anticancer drug like 5 fluorouracil we were able to develop a potential nanoplatform for the multimodal therapy of Neuroblastoma. [Display omitted] • Synthesis of novel Protein-Titanocene Nanocomplex via thermal treatment. • Synthesis of protein core (Titanocene loaded lactoferrin nanoparticles)-ZIF-8 shell MOFs • Molecular dynamics, Quantum mechanical model and spectroscopic investigations • Using QbD approach for optimizing protein titanocene Nanocomplex development. [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf) is a bioactive milk-derived protein with remarkable wide-spectrum antifungal activity. To deepen our understanding of the molecular mechanisms underlying Lf cytotoxicity, the role of plasma membrane ergosterol- and sphingolipid-rich lipid rafts and their association with the proton pump Pma1p was explored. Pma1p was previously identified as a Lf-binding protein. Results showed that bovine Lf (bLf) perturbs ergosterol-rich lipid rafts organization by inducing intracellular accumulation of ergosterol. Using yeast mutant strains lacking lipid rafts-associated proteins or enzymes involved in the synthesis of ergosterol and sphingolipids, we found that perturbations in the composition of these membrane domains increase resistance to bLf-induced yeast cell death. Also, when Pma1p-lipid rafts association is compromised in the Pma1–10 mutant and in the absence of the Pma1p-binding protein Ast1p, the bLf killing activity is impaired. Altogether, results showed that the perturbation of lipid rafts and the inhibition of both Pma1p and V-ATPase activities mediate the antifungal activity of bLf. Since it is suggested that the combination of conventional antifungals with lipid rafts-disrupting compounds is a powerful antifungal approach, our data will help to pave the way for the use of bLf alone or in combination for the treatment/eradication of clinically and agronomically relevant yeast pathogens/fungi. • A novel mechanism underlying lactoferrin antifungal activity was discovered. • Lactoferrin perturbs ergosterol-rich lipid rafts in yeast. • Pma1p-lipid rafts association is critical for lactoferrin-induced cell death. • Lactoferrin inhibits yeast V-ATPase activity. • The novel lipid rafts disrupting activity can be explored for antifungal therapy. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a devastating gastrointestinal tumor with limited Chemotherapeutic options. Treatment is restricted by its poor vascularity and dense surrounding stroma. Quinacrine is a repositioned drug with an anticancer activity but suffers a limited ability to reach tumor cells. This could be enhanced using nanotechnology by the preparation of quinacrine-loaded Undaria pinnatifida fucoidan nanoparticles. The system exploited fucoidan as both a delivery system of natural origin and active targeting ligand. Lactoferrin was added as a second active targeting ligand. Single and dual-targeted particles prepared through nanoprecipitation and ionic interaction respectively were appraised. Both particles showed a size lower than 200 nm, entrapment efficiency of 80% and a pH-dependent release of the drug in the acidic environment of the tumor. The anticancer activity of quinacrine was enhanced by 5.7 folds in dual targeted particles compared to drug solution with a higher ability to inhibit migration and invasion of cancer. In vivo, these particles showed a 68% reduction in tumor volume compared to only 20% for drug solution. In addition, they showed a higher animals' survival rate with no hepatotoxicity. Hence, these particles could be an effective option for the eradication of pancreatic cancer cells. Unlabelled Image • U. pinnatifida fucoidan particles were prepared as single and dual targeted systems. • Both nanoparticles were loaded with quinacrine to enhance activity. • Activity of single and dual active nanoparticles was compared in vitro and in vivo. • Dual targeted nanoparticles showed the highest anticancer activity. • Elaborated nanosystem could also decrease cancer cells' migration and invasion. [ABSTRACT FROM AUTHOR]

A successful drug delivery to a specific site relies on two essential factors including; efficient entrapment of the drug within the carrier and successful delivery of drug- loaded nanocarrier to the target site without opsonisation or drug release in the circulation before reaching the organ of interest. Lactoferrin (LF) is a glycoprotein belonging to the transferrin (TF) family which can bind to TF receptors (TFRs) and LF membrane internalization receptors (LFRs) highly expressed on the cell surface of both highly proliferating cancer cells and blood brain barrier (BBB), which in turn can facilitate its accessibility to the cell nucleus. This merit could be exploited to develop actively targeted drug delivery systems that can easily cross the BBB or internalize into tumor cells. In this review, the most recent advances of utilizing LF as an active targeting ligand for different types of nanocarriers including: inorganic nanoparticles, dendrimers, synthetic biodegradable polymers , lipid nanocarriers, natural polymers, and nanoemulstions will be highlighted. Collectively, LF seems to be a promising targeting ligand in the field of nanomedicine. Unlabelled Image [ABSTRACT FROM AUTHOR]

Lactoferrin is a glycoprotein with a molecular weight of 80 kDa, which produced in many mammalian excretions. LF is involved in various physiological processes and known to possess prominent biocidal activities, serving as an effective agent against a wide range of pathogens. This effective biocidal activity of LF in association with immune system response has made this protein an attractive therapeutic candidate. Interaction of proteins with nanoparticles (NPs) gives rise to the formation of a dynamic NP-protein complex and can induce conformational changes in the adsorbed proteins which may lead to the change in their function. With the recent advances in nanotechnology, NPs may provide the protection and stabilization of LF from hydrolysis by some proteases and increase their uptake by targeted cells. These nanoformulations of LF can be used as diagnosis, disease targeting and drug delivery tools. Owing to its multiple functionalities, LF is a promising active ingredient to be loaded or adsorbed to NPs for preparing a stable, controlled surface NPs. Thus, LF NPs can potentially empower the resulting nanocomplex with attracting functionalities and might be useful in many applications, e.g., to modify the optical or rheological properties of products, or to encapsulate and deliver bioactive ingredients. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) is a naturally glycoprotein with iron-binding properties and diverse biological applications including; antiviral, anti-inflammatory, antioxidant, anti-cancer and immune stimulating effects. In addition, LF was found to be an ideal nanocarrier for some hydrophobic therapeutics because of its active targeting potential due to overexpression of its receptor on the surface of many cells. Moreover, it was proven to be a good candidate for fabrication of nanocarriers to specifically deliver drugs in case of brain tumors owing to the capability of LF to cross the blood brain barrier (BBB). Consequently, it seems to be a promising molecule with multiple applications in the field of cancer therapy and nanomedicine. Unlabelled Image [ABSTRACT FROM AUTHOR]

Electrostatic interactions between actin filaments and myosin molecules, which are ubiquitous proteins in eukaryotes, are crucial for their enzymatic activity and motility. Nonspecific electrostatic interactions between proteins are unavoidable in cells; therefore, it is worth exploring how ambient proteins, such as polyelectrolytes, affect actin-myosin functions. To understand the effect of counterionic proteins on actin-myosin, we examined ATPase activity and sliding velocity via actin-myosin interactions in the presence of the basic model protein hen egg lysozyme. In an in vitro motility assay with ATP, the sliding velocity of actin filaments on heavy meromyosin (HMM) decreased with increasing lysozyme concentrations. Actin filaments were completely stalled at a lysozyme concentration above 0.08 mg/mL. Lysozyme decreased the ATP hydrolysis rate of the actin-HMM complex but not that HMM alone. Co-sedimentation assays revealed that lysozyme enhanced the binding of HMM to actin filaments in the presence of ATP. Additionally, lysozyme could bind to actin and myosin filaments. The inhibitory effect of poly- l -lysine, histone mixture, and lactoferrin on the motility of actin-myosin was higher than that of lysozyme. Thus, nonspecific electrostatic interactions of basic proteins are involved in the bundling of actin filaments and modulation of essential functions of the actomyosin complex. • Lysozyme suppresses the ATPase activity and the motility of actin-myosin system. • Lysozyme can bind to both actin and myosin filaments. • Basic proteins, lactoferrin and histone, also suppress the motility. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is neurological disorder characterized by dementia which causes severe problems with behavior, thinking and memory. Systemic administration of therapeutics to the central nervous system (CNS) is usually associated with very low efficiency due to presence of blood brain barrier (BBB), which only allows permeation of few types of molecules from the circulation to the CNS. As an alternative, naturally amphiphilic micelles can be utilized to enhance targeted drug delivery to the brain. In this sense, lactoferrin (LF) was covalently attached to conjugated linoleic acid (CLA) via carbodiimide coupling reaction to form a new micellar nanoplatform with particle size of about 53 nm. Afterwards, fabricated micelles were further loaded once again with CLA to enhance its delivery to the CNS. In vitro drug release study revealed that CLA exhibited sustained release at pH 6.8, associated with good hemocompatibility without any remarkable in vivo toxicity in terms of liver and kidney functions. Moreover, in vivo studies showed that the fabricated micelles manifested enhanced in vivo biodistrbution in brain tissue due to the active targeting potential of LF. Additionally, drug-loaded LF-CLA micelles exhibited enhanced cognitive capabilities, reduced brain oxidative stress, inflammation, apoptosis and acetylcholine esterase activity, besides a decline in the deposition of amyloid β peptide1–42 in aluminum chloride Alzheimer's-induced animal model. CLA-based micelles could be a promising CNS actively targeted delivery system with a sophisticated potential to reduce AD symptoms. Unlabelled Image • Conjugation between lactoferrin (LF) and conjugated linoleic acid (CLS) was conducted via carbodiimide coupling reaction. • LF-CLA micelles showed enhanced active targeting potential to brain tissue. • LF-CLA micelles reduced oxidative stress in brain tissue. • LF-CLA micelles reduced inflammation and apoptosis in brain tissue. [ABSTRACT FROM AUTHOR]

The influence of physicochemical properties of carrier oils on nanoemulsion stability and the bioaccessibility of lycopene were studied. Lycopene-loaded nanoemulsions were prepared by using sesame oil, linseed oil or walnut oil as the oil phase and lactoferrin as the emulsifier. The stability was investigated by particle size, zeta potential, pH sensitivity, thermal stability and lycopene retention. Results showed that the stability was positively correlated with oil density but negatively related to oil viscosity and unsaturation degree; the lycopene nanoemulsion prepared by sesame oil exhibited greater stability and a slower degradation rate of lycopene compared to the other nanoemulsions. In addition, the lycopene retention in sesame oil-nanoemulsions was significantly higher during the first three weeks of storage. The bioaccessibility of lycopene, as measured by a simulated gastrointestinal model, was greatly improved in the nanoemulsion system. The lycopene bioaccessibility was around 25% in sesame oil- and linseed oil-nanoemulsions, and 18% in walnut oil-nanoemulsions, showing a similar trend with their stability. This information may facilitate the design of more efficacious lycopene-fortified delivery systems. • The stability and bioavailability of the prepared nanoemulsions were studied by using three different vegetable oils. • Provides a reference for the preparation of a stable and efficient nanoemulsion system. • Enables lycopene to enhance its stability and bioaccessibility through a stable and efficient nanoemulsion delivery system. [ABSTRACT FROM AUTHOR]

7,8-dihydroxyflavone (7,8-DHF), a tyrosine kinase B (TrkB) receptor agonist, can mimick physiological actions of brain-derived neurotrophic factor (BDNF) to attenuate neurogenic disease. However, its use as a functional food, is limited by its low-water solubility, chemical instability, and poor bioavailability. The purpose of this work is to fabricate stable 7,8-DHF loaded zein/lactoferrin (LF) composite nanoparticles (zein/LF-DHF) to overcome these challenges. Results showed that mean particle size of zein/LF nanoparticles was about 74 nm with low polydispersity index (<0.200) and turbidity (<0.300) values. Zein/LF nanoparticles had good stability against pH (3.0–9.0), ionic strengths (0–500 mM NaCl at neutral pH) and long-term storage. Zein/LF nanoparticles showed spherical structures formed by hydrogen bonding and hydrophobic interactions, however, LF changed surface morphology of zein nanoparticles as observed by scanning electron microscope. X-ray diffraction indicated 7,8-DHF was presented in an amorphous state inside zein/LF nanoparticles. Most importantly, zein/LF-DHF had good redispersibility, and increased the encapsulation efficiency, chemical stability, water solubility and bioaccessibility of 7,8-DHF. Collectively, zein/LF nanoparticles are promising delivery systems for 7,8-DHF in functional foods. Unlabelled Image • Lactoferrin (LF) acted as a powerful stabilizer to fabricate zein nanoparticles. • 7,8-Dihydroxyflavone (7,8-DHF) was firstly encapsulated in zein/LF nanoparticles. • Zein/LF-DHF had good redispersibility in water. • Zein/LF-DHF increased encapsulation efficiency and chemical stability of 7,8-DHF. • Zein/LF-DHF enhanced water solubility and bioaccessibility of 7,8-DHF. [ABSTRACT FROM AUTHOR]

Fucoidan is a marine polymer extracted from diverse types of brown algae. This polysaccharide showed great potential towards treatment of different types of cancer. In this study, the activity of fucoidan extracted from Undaria Pinnatifida was investigated against pancreatic cancer (one of the most life-threatening cancers). Then, in an attempt to enhance the polymer's activity against cancer cells, conversion the polymer solution to nanoparticles was suggested to enhance its delivery through pancreatic cancer surrounding stroma. Novel fucoidan based nanoparticles were elaborated by polyelectrolyte interaction with the positively charged, active targeting ligand lactoferrin. The formulation was optimized through the interplay between different factors. Effect of fucoidan solution along with its blank nanoparticles was tested on the viability of pancreatic cancer cells and its migration and invasion abilities. Results confirmed the cytotoxic ability of fucoidan against pancreatic cancer. IC 50 value decreased by 2.3 folds when the polymer was converted to nanoparticles. The prepared nanosystems showed an enhanced ability to prevent pancreatic cancer cells' migration and invasion. Results suggested the potential of using these nanoparticles as bioactive dual-targeted system either blank or loaded with different anticancer agents for treatment for pancreatic cancer. Unlabelled Image • Activity of undaria pinnatifida fucoidan was inspected against PANC-1 cells. • Novel fucoidan/lactoferrin nanoparticles were prepared by ionic interaction. • Blank dual targeted bioactive nanoparticles showed enhanced anticancer activity. • Fucoidan and its nanoparticles could inhibit migration and invasion of cancer cells. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HPTC) currently ranks as the third leading cause of cancer-related mortality, necessitating an advanced formulation strategy. Recently, lactoferrin (Lf) has been utilized as a specific targeting ligand in HPTC due to its high specificity towards the asialoglycoprotein receptor expressed in cancer cells. Therefore, we present the fabrication of an Lf-decorated carboxymethyl dextran-encased chitosan-coated europium metal-organic framework-based nanobioconjugate (Lf-CMD-CS-CUR@Eu-MOF) for targeted curcumin (CUR) delivery. Briefly, CUR was loaded into Eu-MOF, followed by coating cationic 'CS' on the CUR@Eu-MOF surface. Simultaneously, Lf-decorated CMD was prepared via an esterification reaction. Subsequently, Lf-CMD-CS-CUR@Eu-MOF was synthesized using the Maillard reaction. Various spectral characterizations, drug entrapment, drug content, in vitro drug release, biocompatibility and cell cytotoxicity studies were performed. It exhibited an entrapment efficiency of 88.87 ± 2.1 %, a drug content of 3.45 ± 0.98 %, and a drug loading rate of 34.85 ± 0.6 mg/g. Furthermore, the Lf-CMD-CS-CUR@Eu-MOF exhibits excellent biocompatibility with normal cells. The in vitro dissolution study confirmed a release of 78.12 % of 'CUR' in pH 5.8 phosphate buffer (over 120 h), attributed to the controlled release rate by the 'CS' coating on the surface of CUR@Eu-MOF. The BEL-7402 cell line showed concentration-dependent toxicity of nanobioconjugate to cancerous cells. Therefore, when 'Lf' is surface-decorated onto an appropriate polymeric material, it gains the capability to function as a carrier for transporting 'CUR' to the precise target site within HPTC. In conclusion, Lf-CMD incorporated CS-coated Eu-MOF can provide a promising approach for targeted drug delivery in HPTC management. [Display omitted] • Lactoferrin-decorated carboxymethyl dextran (Lf-CMD) shell for targeted drug delivery in hepatocellular carcinoma. • Chitosan-coated curcumin-loaded europium metal-organic framework (CS-CUR@Eu-MOF) offered the extended 'CUR' release. • The Lf-CMD-CS-CUR@Eu-MOF nanobioconjugate furnishes the controlled release in an acidic environment (pH 5.8) • Targeted delivery of 'CUR' through Lf functionalization showed improved anticancer activity against BEL-7402. • In the future, the Lf-CMD incorporated CS-CUR@Eu-MOF can be used for the successful management of HPTC. [ABSTRACT FROM AUTHOR]

Increasing demand for high-quality fresh fruits and vegetables has led to the development of innovative active packaging materials that exhibit controlled release of antimicrobial/antioxidant agents. In this study, composite biopolymer films consisting of methylcellulose (MC) and chitosan nanofibers (ChNF) were fabricated, which contained lactoferrin (LAC)-loaded silver-metal organic framework (Ag-MOF) nanoparticles. The results indicated that the nanoparticles were uniformly distributed throughout the biopolymer films, which led to improvements in tensile strength (56.1 ± 3.2 MPa), thermal stability, water solubility, swelling index, water vapor barrier properties (from 2.2 ± 2.1 to 1.9 ± 1.9 × 10−11 g. m/m2. s. Pa), and UV-shielding effects. The Ag-MOF-LAC2% films also exhibited strong and long-lasting antibacterial activity against E. coli (19.8 ± 5.2 mm) and S. aureus (20.1 ± 3.2 mm), which was attributed to the slow release of antimicrobial LAC from the films. The composite films were shown to maintain the fresh appearance of apples for at least seven days, which was attributed to their antimicrobial and antioxidant activities. Consequently, these composite films have the potential in the assembly of innovative active packaging materials for protecting fresh fruits and vegetables. However, further work is required to ensure their safety and economic viability. [Display omitted] [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is one of the leading causes of opportunistic infections such as chronic wound infection that could lead to multiple organ failure and death. Gallium (Ga3+) ions are known to inhibit P. aeruginosa growth and biofilm formation but require carrier for localized controlled delivery. Lactoferrin (LTf), a two-lobed protein, can deliver Ga3+ at sites of infection. This study aimed to develop a Ga-LTf complex for the treatment of wound infection. The characterisation of the Ga-LTf complex was conducted using differential scanning calorimetry (DSC), Infra-Red (FTIR) and Inductive Coupled Plasma Optical Emission Spectrometry (ICP-OES). The antibacterial activity was assessed by agar disc diffusion, liquid broth and biofilm inhibition assays using the colony forming units (CFUs). The healing capacity and biocompatibility were evaluated using a P.aeruginosa infected wound in a rat model. DSC analyses showed thermal transition consistent with apo-lactoferrin; FTIR confirmed the complexation of gallium to lactoferrin. ICP-OES confirmed the controlled local delivery of Ga3+. Ga-LTf showed a 0.57 log 10 CFUs reduction at 24 h compared with untreated control in planktonic liquid broth assay. Ga-LTf showed the highest antibiofilm activity with a 2.24 log 10 CFUs reduction at 24 h. Furthermore, Ga-LTf complex is biocompatible without any adverse effect on brain, kidney, liver and spleen of rats tested in this study. Ga-LTf can be potentially promising novel therapeutic agent to treat pathogenic bacterial infections. [ABSTRACT FROM AUTHOR]

α-Amylase activity differs between individuals and is influenced by dietary behavior and salivary constituents, but limited information is available on the relationship between α-amylase activity and saliva components. This study investigated the impact of salivary proteins on α-amylase activity, their various correlations, the effect of mucin (MUC5B and MUC7) and lactoferrin on the enzymatic kinetics of α-amylase, and the mechanisms of these interactions using the quartz crystal microbalance with dissipation (QCM-D) technique and molecular docking. The results showed that α-amylase activity was significantly correlated with the concentrations of MUC5B (R2 = 0.42, p < 0.05), MUC7 (R2 = 0.35, p < 0.05), and lactoferrin (R2 = 0.35, p < 0.05). An in vitro study demonstrated that α-amylase activity could be significantly increased by mucins and lactoferrin by decreasing the Michaelis constant (K m) of α-amylase. Moreover, the results from the QCM-D and molecule docking suggested that mucin and lactoferrin could interact with α-amylase to form stable α-amylase-mucin and α-amylase-lactoferrin complexes through hydrophobic interactions, electrostatic interactions, Van der Waals forces, and hydrogen bonds. In conclusion, these findings indicated that the salivary α-amylase activity depended not only on the α-amylase content, but also could be enhanced by the interactions of mucin/lactoferrin with α-amylase. [Display omitted] • Mucin and lactoferrin could significantly increase α-amylase activity. • Mucin and lactoferrin decreased the K m of α-amylase. • In saliva, mucin and lactoferrin could interact with α-amylase as stable complexes. • Hydrogen bond was the dominate force for the complexes formation. [ABSTRACT FROM AUTHOR]

The increased mortality rates associated with colorectal cancer highlight the pressing need for improving treatment approaches. While capsaicin (CAP) has shown promising anticancer activity, its efficacy is hampered due to low solubility, rapid metabolism, suboptimal bioavailability, and a short half-life. Therefore, this study aimed to prepare a lactoferrin-functionalized carboxymethyl dextran-coated egg albumin nanoconjugate (LF-CMD@CAP-EGA-NCs) for the targeted CAP delivery to enhance its potential for colorectal cancer therapy. Briefly, LF-CMD was synthesized through an esterification reaction involving LF as a receptor and CMD as a shell. Concurrently, CAP was incorporated into an EGA carrier using gelation and hydrophobic interactions. The subsequent production of LF-CMD@CAP-EGA-NCs was achieved through the Maillard reaction. Spectral characterizations confirmed the successful synthesis of smooth and spherical-shaped LF-CMD@CAP-EGA-NCs using LF-CMD and EGA-CAP nanoparticles, with high entrapment efficiency and satisfactory drug content. Furthermore, LF-CMD@CAP-EGA-NCs demonstrated a sustained release of CAP (76.52 ± 1.01 % in 24 h, R2 = 0.9966) in pH 5.8 buffer with anomalous transport (n = 0.68) owing to the shell of the CMD and EGA matrix. The nanoconjugate exhibited enhanced cytotoxicity in HCT116 and LoVo cell lines, which is attributed to the overexpression of LF receptors in colorectal HCT116 cells. Additionally, LF-CMD@CAP-EGA-NCs demonstrated excellent biocompatibility, as observed in the FHC-CRL-1831 cell line. In conclusion, LF-CMD@CAP-EGA-NCs can be considered as a promising approach for targeted delivery of CAP and other anticancer agents in colorectal cancer treatment. [Display omitted] • Designed lactoferrin (LF) decorated nanosystem for targeted delivery of capsaicin (CAP) in colorectal cancer cells. • Developed LF functionalized carboxymethyl dextran-coated CAP-loaded egg albumin nanoconjugates. • The LF decoration on LF-CMD@CAP-EGA-NCs provided sustained delivery of CAP. • LF-CMD-CAP-EGA-NCs exhibited significantly higher anticancer activity against colorectal cancer cell lines. • LF-decorated CMD-EGA-NCs presents a promising alternative for CAP delivery. [ABSTRACT FROM AUTHOR]

Lactoferrin is a highly glycosylated protein, which have important biological functions in the growth and development of neonates. However, the glycoforms and glycosylation sites differed between species. The aim of the study was to identify the glycosylation profile (including glycosites, glycan structures, and glycoforms) of purified lactoferrin from human and animal (cow, goat, sheep) milk by using site-specific glycoproteomics technique. In total, a number of 89 N-glycans were identified in human and animal milk lactoferrin. We identified three N-glycosites with 23 different compositions of N-glycans in cow lactoferrin (CLF), four distinctive N-glycosites with 34 dissimilar N-glycan compositions in goat lactoferrin (GLF), five N-glycosites with 57 different N-glycan compositions in sheep lactoferrin (SLF), while five unique N-glycosites with 50 different N-glycan compositions were ascertained in human lactoferrin (HLF). HLF had the most complex glycan, while animal lactoferrin had the most high-mannose glycoforms. The results of this study further our understanding of lactoferrin differences between human and animal milk, which can provide a perspective on the analysis of differences in functional characteristics. [ABSTRACT FROM AUTHOR]

In order to meet the market demand and avoid the increase of operation amount and cleaning cost in the process of ultrafiltration, it is particularly important to find more practical and efficient methods to control and improve membrane fouling. In this study, the ions in the ultrafiltration process were regulated to affect membrane surface proteins composition (lactoferrin, α-lactalbumin, β-lactoglobulin A and β-lactoglobulin B) and delay membrane fouling. It was found that Na+ (21 mmol/L), Zn2+ (0.25 mmol/L) and K+ (44 mmol/L) was added at 4 min, 8 min and 12 min, respectively during ultrafiltration process. The continuous regulation slowed down the decline rate of membrane flux and reduced the content of α-lactalbumin, β-lactoglobulin A and β-lactoglobulin B on the membrane surface analyzed by HPLC. This could reduce the irreversible membrane fouling of proteins cake resistance. Furthermore, the ions concentration was also investigated after filtration. The concentration of K+ was increased significantly and other ions concentration was not significantly changed after continuous regulation such Na+, Mg2+, Zn2+ and Ca2+ compared to control. Therefore, dynamic ionic regulation of whey protein ultrafiltration process is a simple and effective method, which provides technical theoretical basis for optimizing and improving membrane technology. A method to control membrane fouling was proposed, which regulated the ion environment around the protein at specific time during ultrafiltration process. The components of the membrane surface proteins (lactoferrin, α-lactalbumin, β-lactoglobulin A and β-lactoglobulin B) were analyzed by HPLC. [Display omitted] • The proteins composition on ultrafiltration membrane surface was analyzed by HPLC. • The ionic around whey protein was regulated to reduce membrane fouling. • The ionic regulation time also affects the membrane fouling process. [ABSTRACT FROM AUTHOR]

Conventional cancer mono-therapeutic approaches including radiotherapy, surgery, and chemotherapy don't always achieve satisfactory outcomes and are frequently associated with significant limitations. Although chemotherapy is a vital intervention, its effectiveness is frequently inadequate and is associated with metastasis, multidrug resistance, off-target effect, and normal cells toxicity. Phototherapies are employed in cancer therapy, encompassing photo-dynamic and photo-thermal therapies which under favorable NIR laser light irradiation initiate the included photosensitizers and photo-thermal agents to generate ROS or thermal heat respectively for cancer cells destruction. Photo-therapy is considered noninvasive, posing no resistance, but it still suffers from several pitfalls like low penetration depth and excessive heat generation affecting neighboring tissues. Improved selectivity and tumor-homing capacity could be attained through surface modulation of nanoparticles with targeting ligands that bind to receptors, which are exclusively overexpressed on cancerous cells. Developing novel modified targeted nanoparticulate platforms integrating different therapeutic modalities like photo-therapy and chemotherapy is a topic of active research. This review aimed to highlight recent advances in proteins, nucleic acids, and biological cell membranes functionalized nanocarriers for smart combinatorial chemotherapy/photo-therapy. Nanocarriers decorated with precise targeting ligands, like aptamers, antibody, and lactoferrin, to achieve active tumor-targeting or camouflaging using various biological cell membrane coating are designed to achieve homologous tumor-targeting. [Display omitted] [ABSTRACT FROM AUTHOR]

Several studies indicate that the disruption of the intestinal epithelial barrier can lead to inflammatory bowel disease (IBD). Recent evidence has increasingly demonstrated that lactoferrin (LF) and osteopontin (OPN) can alleviate intestinal barrier injury. However, the potential synergistic effects of these two proteins and the mechanisms underlying their effects remain unclear. To address this question, we developed a lipopolysaccharide-induced intestinal barrier injury model in C57BL/6 N mice. Our findings demonstrated that the combination of LF and OPN at a 1:5 ratio exerts the strongest protective effect on the intestinal barrier, and it is more effective than LF or OPN alone. This protection is evidenced by the decrease in serum diamine oxidase (DAO) activity (1.66-fold decrease) and D-lactic content (1.51-fold decrease) and the reduced rate of FITC-labeled glucan transport across the jejunum (3.18-fold decrease). Moreover, the protein combination significantly promoted villi length (1.66-fold increase) and crypt depth (1.57-fold increase), improved tight junction protein structure and expression, and boosted the number of absorptive cells (4.34-fold increase) in the intestinal epithelium. Furthermore, the combination promoted crypt cell proliferation and differentiation via Notch signaling. In summary, our findings provide scientific evidence supporting the use of dietary intervention strategies for preventing IBD. [ABSTRACT FROM AUTHOR]

The paper describes the development of a novel DNA oligonucleotide-based affinity bioreceptor that binds to lactoferrin, a glycoprotein-type immunomodulator. The research was performed using surface plasmon resonance method to investigate affinity of various types of oligonucleotides to the target protein. The 72 base pair-long 5′[(TAGAGGATCAAA)AAA] 4 TAGAGGATCAAA3' sequence with the highest affinity to lactoferrin was selected for further investigations. Kinetic analysis of the interaction between selected DNA and lactoferrin provided rate and equilibrium constants: k a = (2.49 ± 0.03)∙104 M−1∙s−1, k d = (1.89 ± 0.02)∙10−3 s−1, K A = (0.13 ± 0.05)∙108 M−1, and K D = (7.61 ± 0.18)∙10−8 M. Thermodynamic study conducted to determine the ΔH 0 , ΔS 0 , and ΔG 0 for van't Hoff characteristic in the temperature range of 291.15–305.15 K, revealed the complex formation as endothermic and entropically driven. The chosen DNA sequence's selectivity towards lactoferrin was confirmed with interferents' response constituting <3 % of the response to lactoferrin. SPR analysis justified utility of the designed DNA oligonucleotide for Lf determination, with LOD of 4.42∙10−9 M. Finally, the interaction between lactoferrin and DNA was confirmed by electrochemical impedance spectroscopy, providing the basis for further quantitative assay of lactoferrin using the developed DNA-based bioreceptor. The interactions were performed under immobilized DNA ligand conditions, thus reflecting the sensor's surface, which facilitates their transfer to other label-free biosensor technologies. [ABSTRACT FROM AUTHOR]

The present study investigated on the emulsifying properties of natural low-methoxyl pectin (LMP) extracted from Green Jelly Leaf (GJLP) in stabilising lactoferrin stabilised oil-in-water emulsions. The emulsion stability of GJLP was compared to commercial pectins with different degree of esterification (DE) i. e. high-methoxyl pectin (HMP) and LMP. The influence of pH, pectin types and concentration on the stability and physical properties of emulsions were evaluated by determining zeta potential value, particle size, microstructure, rheological properties and creaming stability. Different types of pectin exhibited different mechanisms in providing the emulsion stability and the pectin effective charge was strongly dependent on its DE and pH of the continuous phase. The mechanism of actions of pectin and lactoferrin in the system were pH dependent for low molecular weight pectin, however not for high molecular pectin such as GJLP. The results showed that the complexes formed by pectin and lactoferrin at the interface were not sufficient to maintain the emulsion stability. This study also showed the important of unabsorbed pectin molecules in continuous phase in providing the physical stability of emulsion. These molecules formed a thick multilayers surround oil droplets. In addition, the incorporation of 0.2% w/w of GJLP could produce a stable emulsion, suggesting the potential use of GJLP to improve the stability of lactoferrin stabilised oil-in-water emulsions. • Pectin-lactoferrin complexes were able to enhance the stability of the emulsion. • Pectin with high molecular weight has a better emulsifying properties than low molecular weight pectin. • Incorporation of green jelly leaf pectin has developed a stabilised emulsion with small droplet sizes. • The stabilisation mechanism of green jelly leaf pectin is pH independent. [ABSTRACT FROM AUTHOR]

Life manifestation is mainly based on biopolymer-ligand molecular recognition; therefore, the elucidation of energy and speed associated with protein-ligand binding is strategic in understanding and modulating biological systems. In this study, the interactions between methylene blue (MB) or azure A (AZA) dyes and bovine lactoferrin (BLF) were investigated by surface plasmon resonance, fluorescence spectroscopy, and isothermal titration microcalorimetry. Despite the molecular similarities between the dyes, the BLF-AZA binding thermodynamic parameters (ΔG AZA o = −30.50 and ΔH AZA o = 10.8 (kJ·mol−1)) were higher in magnitude than those of the BLF-MB systems (ΔG MB o = −27.3 and ΔH MB o = 5.72 (kJ·mol−1)). To increase the systems' entropy (TΔS AZA o = 41.3 and TΔS MB o = 33.0 (kJ·mol−1)), the hydrophobic interactions must outweigh the electrostatic repulsion, thereby promoting BLF-dye binding. The activation complex formation (E ac , a MB = 33, E ac , a AZA = 32, ∆H a, MB ‡ = 31, ∆H a, AZA ‡ = 30, ∆G a, MB ‡ = 51.84, ∆G a, AZA ‡ = 50.7, T∆S a, MB ‡ = −21, T∆S a, AZA ‡ = −21 (kJ·mol−1)), owing to free BLF and MB (or AZA) associations, was not affected by the dye chemical structure, while for the thermodynamically stable BLF-dye complex dissociation, the same energetic parameters (E ac , d MB = 16, E ac , d AZA = 6.4, ∆H d, MB ‡ = 14, ∆H d, AZA ‡ = 3.9, ∆G d, MB ‡ = 81.4, ∆G d, AZA ‡ = 74.93, T∆S d, MB ‡ = −68, T∆S d, AZA ‡ = −71.0 (kJ·mol−1)) were considerably affected by the number of methyl groups. Our results may be very useful to determine binding processes controlled by kinetic parameters, as well as to optimize the application of these photosensitive dyes in biological systems. Unlabelled Image • Lactoferrin interacts with methylene blue or azure A dyes. • Kinetic and thermodynamic binding parameters are dye chemical structure dependent. • Entropic factors were the driving forces for apo-BLF/phenothiazine dye interaction. • Holo-BLF/phenothiazine dye interaction was enthalpy driven. • Dye (-CH 3) groups number decrease make BLF/phenothiazine dye interaction stronger. [ABSTRACT FROM AUTHOR]