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The development of new drug therapies for Alzheimer's disease (AD) is an important research topic today, but the pathogenesis of AD has not been thoroughly studied, and there are still several shortcomings in existing drug therapies. Therefore, this study aimed to explore the molecular mechanism of lactoferrin (LF) in the treatments of AD and ulcerative colitis (UC) that is susceptible to AD, starting from the principle of one drug, two diseases, and the same treatment. This study used pathological staining and specific indicator staining to preliminarily evaluate the interventions of LF on UC injury and AD progression. We also used 16s RNA full-length sequencing to investigate the effect of LF on the abundance of intestinal microbiota in AD mice. Intestinal tissue and brain tissue metabolomics analysis were then used to screen specific metabolic pathways and preliminarily verify the metabolic mechanism of LF in alleviating the 2 diseases by regulating certain specific metabolites. Moreover, LF significantly changed the types and abundance of gut microbiota in AD mice complicated by UC. To conclude, this study proved the clinical phenomenon of AD susceptibility to UC, and verified the therapeutic effect of LF on 2 diseases. More importantly, we revealed the possible molecular mechanism of LF: Not only does it enrich the cognitive level of LF in alleviating AD by regulating the gut microbiota through the brain gut axis from the perspective of the theory of food nutrition promoting human health, but it also provides a practical basis for the subsequent research and development of LF and drug validation from the perspective of drug food homology. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

• The present study focuses on the use of natural substances like vitamin C, folic acid, and lactoferrin to stimulate the phenylpropanoid pathway in germinating fenugreek sprouts. • Among the different genotypes studied, germinated fenugreek sprouts of the IM6 genotype pre-treated with 500 µM vitamin C (T1) demonstrated the highest increase in total phenolic content and antioxidant activity on the 4th day of germination. • The T1-treated IM3 fenugreek sprouts also exhibited the most significant anti-hyperglycemic activity. They were able to inhibit the activities of key enzymes involved in carbohydrate digestion, including α-amylase, α-glucosidase, and invertase under in vitro conditions. • The treatments did not significantly affect the levels of diosgenin and trigonelline in germinating sprouts. These compounds are known for their health benefits and remained relatively stable during germination. • Notably, the quercetin content in T1-treated germinating sprouts continued to increase, even beyond the fourth day of germination. Quercetin is a type of flavonoid with antioxidant properties. • The study established a positive correlation between the increase in total phenol content, especially quercetin, and the antioxidant potential as well as anti-diabetic activity observed in the 4th day germinated sprouts. • These findings suggest that using T1-treated fenugreek sprouts may be a promising dietary approach for managing diabetes-related hyperglycemia and oxidative stress. The present study investigated the use of natural elicitors (vitamin C, folic acid, and lactoferrin) to stimulate the phenylpropanoid pathway in germinating fenugreek sprouts, with the aim of increasing their total phenolic phytochemical compounds responsible for imparting antioxidant and anti-hyperglycemic properties. Observations revealed that germinating fenugreek sprouts of the IM3 genotype, pre-treated with 500 µM vitamin C (T1) on the 4th day, exhibited maximal elicitation of total phenolic content (3680 mg/100 g DW) and antioxidant activity (2607.5 µM/100 g DW) compared to other genotypes. Moreover, T1-treated IM3 fenugreek sprouts demonstrated the highest anti-hyperglycemic activity by inhibiting α-amylase (48.96%), α-glucosidase (92.60%), and invertase (45.65%) enzyme activities under in vitro conditions. Interestingly, the selected treatments did not affect the diosgenin and trigonelline content of germinating sprouts, which decreased in a time-dependent manner during germination. However, the quercetin content (0.01365%) of T1-treated germinating sprouts continued to increase appreciably, even after the 4th day of germination. A direct positive correlation was established between the increase in total phenols, especially quercetin, and the antioxidant potential as well as the anti-hyperglycemic activity in germinated fenugreek sprouts on the 4th day. Thus, T1-treated sprouts hold promise for managing diabetes-related hyperglycemia and oxidative stress, emphasizing the efficacy of vitamin C in enhancing their bioactive properties. This research pioneers the use of natural elicitors to enhance the health benefits of fenugreek sprouts, notably by identifying an optimal treatment and elucidating quercetin dynamics during germination. Such findings are pivotal for advancing our understanding of sprouting processes and provide valuable insights into the development of therapeutic functional foods. However, further research is necessary to validate their efficacy before considering them as futuristic functional foods. [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]

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]

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]

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 use of prostheses in the oral cavity creates favorable conditions for Candida colonization, which may subsequently lead to Candida -associated denture stomatitis (CADS). Due to its many contributing factors and frequent relapses, CADS is difficult to manage. Given the rise in drug resistance among fungal species, it is critical to develop new therapeutic approaches, reduce the required dosage of medications, and minimize the toxicity and side effects of therapy. Salivary lactoferrin, a multifunctional glycoprotein, is thought to be the first line of defense against microbial invasion of mucosal surfaces. Current research emphasizes the capability of lactoferrin and its derivatives to eliminate a broad spectrum of Candida species. It may be an appealing option for use in monotherapy or in combination with common medications for oral stomatitis treatment. This review provides an overview of the current understanding of lactoferrin's anti-fungal effects in oral candidiasis. [Display omitted] [ABSTRACT FROM AUTHOR]

Ferroptosis has emerged as a promising therapeutic approach for glioma. However, its efficacy is often compromised by the activated GPX4-reduced glutathione (GSH) system and the poor brain delivery efficiency of ferroptosis inducers. Therefore, suppression of the GPX4-GSH axis to induce the accumulation of lipid peroxides becomes an essential strategy to augment ferroptosis. In this study, we present a metalloimmunological strategy to target the GPX4-GSH axis by inhibiting the cystine/glutamate antiporter system (system Xc−) and glutathione synthesis. To achieve this, we developed a complex of diethyldithiocarbamate (DDC) chelated with copper and ferrous ions (DDC/Cu-Fe) to trigger T-cell immune responses in the tumor microenvironment, as well as to inhibit tumor-associated macrophages, thereby alleviating immunosuppression. To enhance brain delivery, the DDC/Cu-Fe complex was encapsulated into a hybrid albumin and lactoferrin nanoparticle (Alb/LF NP), targeting the nutrient transporters (e.g., LRP-1 and SPARC) overexpressed in the blood-brain barrier (BBB) and glioma cells. The Alb/LF NP effectively promoted the brain accumulation of DDC/Cu-Fe, synergistically induced ferroptosis in glioma cells and activated anticancer immunity, thereby prolonging the survival of glioma-bearing mice. The nanoformulation of DDC/Cu-Fe provides a promising strategy that combines ferroptosis and metalloimmunology for glioma treatment. Albumin and lactoferrin hybrid nanoparticles (Alb/LF NP) loaded with DDC/Cu-Fe are developed for glioma therapy by activating anti-tumor immunity and inducing ferroptosis. The Alb/LF NP can efficiently target the glioma, remodel the immune microenvironment, and suppress the GSH/GPX4 system to augment ferroptosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Calf diarrhea, a common disease mainly induced by Escherichia coli infection, is one of the main reasons for nonpredator losses. Hence, an effective nonantibacterial approach to prevent calf diarrhea has become an emerging requirement. This study evaluated the microalgae Schizochytrium sp. (SZ) and lactoferrin (LF) as a nutrient intervention approach against E. coli O101:K99-induced preweaning calve diarrhea. Fifty 1-d-old male Holstein calves were randomly divided into 5 groups (n = 10): (1) control, (2) blank (no supplement or challenge), (3) 1 g/d LF, (4) 20 g/d SZ, or (5) 1 g/d LF plus 20 g/d SZ (LFSZ). The experimental period lasted 14 d. On the morning of d 7, calves were challenged with 1 × 1011 cfu of E. coli O101:K99, and rectum feces were collected on 3, 12, 24, and 168 h postchallenge for the control, LF, SZ, and LFSZ groups. The rectal feces of the blank group were collected on d 14. Data were analyzed using the mixed procedure of SAS (version 9.4; SAS Institute Inc.). The E. coli K99 challenge decreased the average daily gain (ADG) and increased feed-to-gain ratio (F:G) and diarrhea frequency (control vs. blank). Compared with the control group, the LFSZ group had a higher ADG and lower F:G, and the LFSZ and SZ groups had lower diarrhea frequency compared with the control group. In addition, the LFSZ and SZ groups have no differences in diarrhea frequency compared with the blank group. Compared with the control group, the blank group had lower serum nitric oxide (NO), endothelin-1, d -lactic acid (D-LA), and lipopolysaccharide (LPS) concentrations, as well as serum IgG, IL-1β, IL-6, IL-10, and TNF-α levels on d 7 and 14. On d 7, compared with the control group, all treatment groups had lower serum NO level, the SZ group had a lower serum D-LA concentration, and the LF and LFSZ groups had lower serum LPS concentration. On d 14, compared with the control group, the fecal microbiota of the blank group had lower Shannon, Simpson, Chao1, and ACE indexes, the LFSZ group had lower Shannon and Simpson indexes, the SZ and LFSZ groups had a higher Chao1 index, and all treatment groups had a higher ACE index. In fecal microbiota, Bifidobacterium and Actinobacteria were negatively associated with IL-10 and d -lactate, while Akkermansia was negatively associated with endothelin-1 and positively correlated with LPS, fecal scores, and d -lactate levels. Our results indicated that LF and SZ supplements could alleviate E. coli O101:K99-induced calf diarrhea individually or in combination. Supplementing 1 g/d LF and 20 g/d SZ could be a potential nutrient intervention approach to prevent bacterial diarrhea in calves. [Display omitted] [ABSTRACT FROM AUTHOR]

Vascular endothelial dysfunction (ED) is one of the mechanisms underlying obesity-related hypertension. Perivascular adipose tissue (PVAT) surrounds blood vessels and influences the vascular endothelium function. Previous studies have demonstrated the antihypertensive effects of lactoferrin (LF) and its hydrolysates through various mechanisms. However, the effect of LF on ED and PVAT has not yet been investigated. In this study, we examined the influence of LF on ED and PVAT using high-fat diet mice as well as MAEC cells and 3T3-L1 adipocytes. Finally, LF supplementation decreases the systolic blood pressure (SBP), serum adhesion molecule (ICAM-1 and VCAM-1), and aorta ROS levels, and improves endothelium-dependent relaxation function in high-fat diet mice. Moreover, LF supplementation down-regulates the Tak1/IL-18/eNOS pathway between PVAT and aorta and enhances the NO generation in high-fat diet mice. In addition, we observe that LF decreases the expression levels of IL-18 and p-Tak1 in 3T3-L1 adipocytes, but fails to influence the eNOS and p-eNOS expression levels in MAEC cells. Finally, the significant associations between LF and IL-18 and SBP and hypertension risk are also observed in obesity children only. These findings provide evidence that the Tak1/IL-18/eNOS pathway between the aorta and PVAT is important in obesity-related ED, and LF may improve ED or even hypertension by down-regulating this pathway. [Display omitted] • LF improves the generation of NO and endothelium-dependent vasodilation in high-fat feed mice. • LF down-regulates the Tak1/IL-18/eNOS pathway between PVAT and aorta. • LF fails to increase the expression of p-eNOS and NO generation in MAEC cells. • LF inhibits the expression levels of p-Tak1 and IL-18 in 3T3-L1 adipocytes. • Serum LF level negatively associates with hypertension risk in obese children only. [ABSTRACT FROM AUTHOR]

Currently, there is growing interest in the potential use of lactoferrin (LTF), a member of the transferrin family, for the improvement of tissue healing. In this sense, a literature search was conducted to integrate data published on the effect of LTF on jawbone repair. PubMed/MEDLINE, Scopus, Embase, Web of Science, LILACS, and Cochrane databases were retrieved according to the PRISMA 2020 statement. Articles in English, Spanish, and Portuguese were recovered, with no year restriction. In vitro, in vivo, and clinical studies were selected. A total of 742 articles were retrieved, 11 of which met the inclusion criteria (5 in vitro and 5 in vivo studies, and one clinical trial). The included data demonstrated wide variations in study design and LTF therapy protocols. Cell proliferation and viability were the primary outcomes evaluated in the in vitro studies, all of which reported a potential effect of LTF on the repair process. Of three in vivo studies, one reported a reduction in the overall healing rate, whereas the other two showed that LTF inhibited bone resorption and increased bone formation. The clinical trial's findings showed that LTF is a potential promoter of wound repair in patients with medication-related osteonecrosis of the jaws. Overall, data from the studies support a potential effect of LTF therapy on the process of jawbone repair. [ABSTRACT FROM AUTHOR]

The multifaceted effects of lactoferrin (LF) on the digestive and immune systems make it an attractive therapeutic option in inflammatory bowel diseases. In this study, we aimed to explore the anti-inflammatory effects of LF in colitis, particularly in relation to cellular senescence. We hypothesize that LF has the potential to modulate the senescence process. The effects of LF on senescence were tested in vitro using HCT116 and SW480 cell lines, and in vivo, the dextran sulfate sodium–induced mouse model of colitis. LF (500 mg/kg) alleviated symptoms of colitis in mice with a significant decrease in colon damage (P <.0001 vs. control) and microscopic (P <.05 vs. control) scores. Cellular senescence markers p16 and p21 were significantly upregulated in the mouse colon during inflammation (both P <.01 vs. control), and LF at 500 mg/kg decreased these markers (both P <.05 vs. dextran sulfate sodium–treated mice). In vitro, LF significantly affected the expression of p16 and p21 (P <.05– P <.0001 vs. control), senescence associated secretory phenotype (P <.01– P <.0001 vs. control), and telomere-specific proteins: telomeric repeat binding factor 1 and 2 (P <.05– P <.0001 vs. control) in a concentration-dependent manner. LF modulates the expression of cellular senescence markers and shows hallmarks of senolytic and pro-senescent activity, depending on dose. Further studies are needed to fully understand the anti-inflammatory effect of LF in the context of senescence and safe utilization in patients with inflammatory bowel diseases. Administration of lactoferrin (LF) in dextran sulfate sodium (DSS)-colitis mice effectively mitigates the effects of colitis-induced intestinal inflammation by reducing senescence markers (p16, p21) and suppressing the upregulation of telomere-binding proteins (TRF1, TRF2), thereby demonstrating its potential as a promising therapeutic intervention. Created with BioRender. [Display omitted] [ABSTRACT FROM AUTHOR]

The majority of bioactive substances in the human diet come from polyphenols. Here, we use spectroscopy, molecular docking, molecular dynamics simulations, and in vitro digestion to look at the relationship between caffeine (CAF) and bovine lactoferrin (BLF). The correlation analysis of the CAF-BLF fluorescence quenching process revealed that the reaction was spontaneous and that the CAF-BLF fluorescence quenching process may have been static. The predominant intrinsic binding forces were hydrogen bonds and van der Waals forces, which were also supported by molecular docking and molecular dynamics simulations. Through Fourier infrared and circular dichroism spectroscopy experiments, it was found that CAF changed the secondary structure of BLF and might bind to the hydrophobic amino acids of BLF. Compared with BLF, CAF-BLF showed inhibitory effects on digestion in simulated in vitro digestion. It will be helpful to better understand the interaction between CAF and BLF and provide the basis for the development of innovative dairy products. [ABSTRACT FROM AUTHOR]

The current study was conducted to examine the effect of l -carnitine (LC) supplementation on telomere length and mitochondrial DNA copy number (mtDNAcn) per cell in mid-lactation cows challenged by lipopolysaccharide (LPS) in blood and liver. The mRNA abundance of 31 genes related to inflammation, oxidative stress, and the corresponding stress response mechanisms, the mitochondrial quality control and the protein import system, as well as the phosphatidylinositol 3-kinase/protein kinase B pathway, were assessed using microfluidics integrated fluidic circuit chips (96.96 dynamic arrays). In addition to comparing the responses in cows with or without LC, our objectives were to characterize the oxidative and inflammatory status by assessing the circulating concentration of lactoferrin (Lf), haptoglobin (Hp), fibrinogen, derivates of reactive oxygen metabolites (dROM), and arylesterase activity (AEA), and to extend the measurement of Lf and Hp to milk. Pluriparous Holstein cows were assigned to either a control group (CON, n = 26) or an LC-supplemented group (CAR; 25 g LC/cow per day; d 42 ante partum to d 126 postpartum (PP), n = 27). On d 111 PP, each cow was injected intravenously with LPS (Escherichia coli O111:B4, 0.5 µg/kg). The mRNA abundance was examined in liver biopsies of d −11 and +1 relative to LPS administration. Plasma and milk samples were frequently collected before and after the challenge. After LPS administration, circulating plasma fibrinogen and serum dROM concentrations increased, whereas AEA decreased. Moreover, serum P4 initially increased by 3 h after LPS administration and declined thereafter irrespective of grouping. The Lf concentrations increased in both groups after LPS administration, with the CAR group showing greater concentrations in serum and milk than the CON group. After LPS administration, telomere length in blood increased, whereas mtDNAcn per cell decreased; however, both remained unaffected in liver. For mitochondrial protein import genes, the hepatic mRNA abundance of the translocase of the mitochondrial inner membrane (TIM)- 17B was increased in CAR cows. Moreover, TIM23 increased in both groups after LPS administration. Regarding the mRNA abundance of genes related to stress response mechanisms, 7 out of 14 genes showed group × time interactions, indicating a (local) protective effect due to the dietary LC supplementation against oxidative stress in mid-lactating dairy cows. For mtDNAcn and telomere length, the effects of the LPS-induced inflammation were more pronounced than the dietary supplementation of LC. Dietary LC supplementation affected the response to LPS primarily by altering mitochondrial dynamics. Regarding mRNA abundance of genes related to the mitochondrial protein import system, the inner mitochondrial membrane translocase (TIM complex) seemed to be more sensitive to dietary LC than the outer mitochondrial membrane translocase (TOM complex). [ABSTRACT FROM AUTHOR]

The survival of living organisms depends on iron, one of the most abundant metals in the Earth's crust. Nevertheless, this micronutrient is poorly available in our aerobic atmosphere as well as inside the mammalian host. This problem is circumvented by the expression of high affinity iron uptake machineries, including the production of siderophores, in pathogenic fungi. Here we demonstrated that F. pedrosoi , the causative agent of the neglected tropical disease chromoblastomycosis, presents gene clusters for siderophore production. In addition, ten putative siderophore transporters were identified. Those genes are upregulated under iron starvation, a condition that induces the secretion of hydroxamates, as revealed by chrome azurol S assays. RP-HPLC and mass spectrometry analysis allowed the identification of ferricrocin as an intra- and extracellular siderophore. F. pedrosoi can grow in different iron sources, including the bacterial ferrioxamine B and the host proteins ferritin, hemoglobin and holotransferrin. Of note, addition of hemoglobin, lactoferrin and holotransferrin to the growth medium of macrophages infected with F. pedrosoi enhanced significantly fungal survival. The ability to produce siderophores in iron limited conditions added to the versatility to utilize different sources of iron are strategies that certainly may contribute to fungal survival inside the host. [ABSTRACT FROM AUTHOR]

Lactoferrin is an iron-binding glycoprotein of the transferrin family that is found in most bodily fluids of mammals and has a variety of biological and beneficial functions, with great importance in health enhancement as a supplement for humans and other animals. More than 300 t of lactoferrin were produced in 2021, and this number is expected to grow yearly by 10% to 12%, to over 580 t in 2030. With new and important functions of lactoferrin being revealed and studied, focus on its industrial production and application is increasing accordingly. However, lactoferrin is mainly sourced from cheese whey or skim milk by cation-exchange column chromatography, which is a costly and low-quality method. A potential solution for lactoferrin global supply chain construction is proposed in this article as a complement to traditional routes of purification from whey or skim milk. The large-scale production of lactoferrin, mainly by recombinant yeast, mammal, and grain systems, as well as the market niche and product design, are discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] The most dangerous type of high-grade astrocytoma is glioblastoma multiforme. The objective of the work was to engineer lactoferrin conjugated temozolomide and resveratrol co-loaded NLC for the treatment of glioblastoma using intranasal delivery for brain targeting. Synergistic activity of temozolomide and resveratrol was determined using combination index method and 1:1 ratio was selected. QbD approach was used to formulate and optimize NLC, with minimum particle size, maximum transmittance and entrapment efficiency using Central Composite Rotable Design (CCRD) method. The optimized LTR-NLC had desired average particle size (209.3 nm), narrow PDI along, high percentage transmittance (>95%) and better entrapment efficiency (95.26% of TEM and 87.59% of RES). From ex-vivo permeation studies it was found that the permeation at 24 h was 77.43 %, and 88.55 % from LTR-NLC and 25.76 % and 31.10% from suspension for resveratrol and temozolomide respectively. In comparison to drug suspension, NLC had nearly 3-fold increase in drug penetration. IC50 value was also significantly better in the groups treated with LTR-NLC. Hence it can be concluded that LTR-NLC may be an effective formulation for the treatment of glioblastoma, according to the findings of this investigation. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis is a major health issue that might lead to hepatic cirrhosis and cancer. One of its main causes is cholestasis, which has been stimulated by bile duct ligation (BDL) to block the bile flow from the liver. As for the treatment, lactoferrin (LF), the iron-binding glycoprotein, has been evaluated in various studies for the treatment of infections, inflammation, and cancer. The current study aims to investigate the curative effects of LF on BDL-induced hepatic fibrosis in rats. Rats were randomly allocated into 4 groups: (1) Control sham, (2) BDL: that have been subjected to a surgery of BDL, (3) BDL + LF: 14 days later after surgery; they have been subjected to LF treatment (300 mg/kg/day, po) for two weeks, and (4) LF group has been administered (300 mg/kg/day, po) for two weeks. BDL elevated inflammatory markers (tumor necrosis factor-alpha and interleukin -1beta (IL-1β) by 635% and 250% (P ≤ 0.05), respectively, as sham group), beside it decreased the anti-inflammatory cytokine, interleukin- 10 (IL-10) by 47.7% (P ≤ 0.05) as sham group, causing inflammation, and fibrosis of the liver by the up-regulation of transforming growth factor-beta 1 (TGF-β1)/Smad2/α-smooth muscle actin (SMA) signaling pathway. LF treatment ameliorated these effects through its anti-inflammatory action (it significantly decreased tumor necrosis factor-alpha and IL-1β by 166% and 159% (P ≤ 0.05), respectively, as sham group, while increased IL-10 by 86.8% (P ≤ 0.05), as sham group) and anti-fibrotic effect by the down-regulation of TGF-β1/Smad2/α-SMA signaling pathway. These results were confirmed by histopathological examination. lactoferrin shows promising results for the treatment of hepatic fibrosis via attenuating the TGF-β1/Smad2/α-SMA pathway and through its properties. [Display omitted] • Liver fibrosis is a major health problem that may progress to cirrhosis and cancer. • Cholestatic liver injury is one of the most important factors for liver fibrosis. • Lactoferrin showed a role in the treatment of bile duct ligation-induced liver fibrosis. • The anti-inflammatory action of lactoferrin might share a part in the treatment. • The treatment by lactoferrin may be via attenuating transforming growth factor-beta1/Smad2/α-SMA signaling pathway. [ABSTRACT FROM AUTHOR]

The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is a first line agent used in the clinic for glioblastoma and it has been useful in increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, such as a short plasma half-life (2 h), is subjected to P-gp efflux, and has limited extravasation from blood to brain (∼20%). It has been postulated that reducing its efflux and increasing glioblastoma tissue exposure to TMZ could prove useful in treating glioblastoma and preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have been loaded with TMZ, surface PEGlyated to reduce efflux and decorated with the cascade targeting protein lactoferrin for efficient uptake across the BBB and into glioblastoma. Our results demonstrate that USLP improves permeability of BBB in vitro as evidenced using a transwell model which mimics endothelial tight junctions with permeation being enhanced using PEGylated particles. Data from TMZ loaded USLP in vitro transwell BBB model also suggests that the USLP formulations can significantly reduce the efflux ratio of TMZ. In vitro apoptosis studies on glioblastoma cell lines U87 and GL261 were conducted which showed an improvement in TMZ induced glioblastoma apoptosis with USLP formulations compared to pure TMZ. Finally, a proof-of-concept preclinical mouse study demonstrated that when given intravenously at 50 mg/kg, USLP particles showed accumulation in the brain within a few hours without any obvious pathophysiological changes in vital organs as assessed via histology. Overall, the data suggests our innovative delivery system is efficient in extravasation from blood and permeating the BBB and has potential to improve efficacy of TMZ in glioblastoma therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a central nervous system disease with poor prognosis. Curative treatments for GBM involve chemotherapy, radiotherapy, and surgical pathways. Recently, antiangiogenic therapy through medications has been tried to slow tumor growth, but the drugs can induce side effects. To overcome these limitations, we developed a new orally absorbable form of heparin that can attenuate angiogenic activity by binding to growth factors around the tumor tissue. We conjugated lactoferrin (Lf) to heparin because Lf can be orally absorbed, and it interacts with the lactoferrin receptor (Lf-R) expressed on the intestine, blood-brain barrier (BBB), and glioma tumor masses. We successfully conjugated Lf and heparin by amide bond formation, as evidenced by advanced physicochemical properties such as pharmacokinetics and stability in acidic condition. This new material inhibited angiogenesis in vitro without toxicity. In addition, Lf-heparin administered orally to GBM orthotopic mice was absorbed in the small intestine and delivered specifically to the brain tumor by receptor transcytosis (Lf-R). Lf-heparin further attenuated angiogenesis progression in GBM orthotopic mice. Based on these results, Lf-heparin shows potential as a new oral medication for treatment of glioblastoma. [Display omitted] [ABSTRACT FROM AUTHOR]

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]

The use of gentamicin (GNT) is associated with acute kidney injury (AKI). Ferroptosis is a newly recognized iron-dependent, non-apoptotic cell death that can lead to AKI. Lactoferrin (LF), an iron-binding glycoprotein, was previously reported to be renoprotective. Nonetheless, LF's impact on GNT-induced AKI and ferroptosis has not yet been investigated. Accordingly, we assessed the dose-dependent effect of LF on GNT-induced AKI and its influence on ferroptosis. Thirty-six male rats were allocated as control, LF, GNT (100 mg/kg/day, i.p.), and groups given LF (100, 200, and 300 mg/kg, p.o.) for 14 days prior concurrently with GNT (Day 8–14). The high dose of LF (300 mg/kg) showed better histopathological picture, higher creatinine clearance, reduced serum and urine levels of kidney injury markers when compared to the GNT group and the lower two doses. These nephroprotective effects of LF can be attributed to the observed reduction in renal ferrous iron, 4-HNE, and MDA, miR-378a-3p and ALOX15 expression, TFR1, NCOA4, and ACSL4 protein expression and the increased LINC00618 expression, GSH levels, GPX4, SLC7A11, and FSP1 protein expression. In conclusion, LF high dose was the most renoprotective against GNT-induced AKI, in which suppression of ferroptosis pathways was a likely contributor to its protective mechanism. [Display omitted] • Ferroptosis is involved in gentamicin (GNT)-induced acute kidney injury (AKI). • Lactoferrin (LF) treatment mitigated GNT-induced AKI in a dose-dependent manner. • LF can be renoprotective via inhibition of ACSL4/TFR1/NCOA4 ferroptosis pathways. • LF via enhancement of SLC7A11, GPX, and FSP1 can inhibit ferroptosis. • LF lessened the expression of miR-378a-3p and LINC00618 involved in ferroptosis. [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf) is a multifunctional protein in the transferrin family. It is involved in many physiological functions, including the regulation of iron absorption and immune response. It also has antibacterial, antiviral, anti-inflammatory, anticancer and antioxidant capabilities under pathophysiological conditions. The mammalian lactoferrin receptor (LfR) plays a key role in mediating multiple functions of Lf. Studies have shown that Lf/LfR is abnormally expressed in the brain of Parkinson's disease, and the excessive accumulation of iron in the brain caused by the overexpression of Lf and LfR is considered to be one of the initial causes of the degeneration of dopaminergic neurons in Parkinson's disease. On the other hand, a number of recent studies have reported that Lf/LfR has a significant neuroprotective effect on Parkinson's disease. In other words, it seems paradoxical that Lf/LfR has both neurodegenerative and neuroprotective effects in Parkinson's disease. This article focuses on recent advances in the possible mechanisms of the neurodegenerative and neuroprotective effects of Lf/LfR in Parkinson's disease and discusses why Lf/LfR has a seemingly contradictory role in the development of Parkinson's disease. Based on the evidence obtained so far, we believed that Lf/LfR has a neuroprotective effect on Parkinson's disease, while as to whether the overexpressed Lf/LfR is the cause of the development of Parkinson's disease, the current evidence is insufficient and further investigation needed. • Why Lf/LfR has a seemingly contradictory role in PD is unclear. • The available evidence supports that Lf/LfR has a neuroprotective effect in PD. • There is currently insufficient evidence on whether overexpressed Lf/LfR is a primary cause of PD. • There is a need to understand the role of Lf/LfR in PD, especially from human studies and clinical Settings. [ABSTRACT FROM AUTHOR]

In this study, carrageenan (CG), xanthan gum (XG) and locust bean gum (LBG), which can be used in infant formulas in China national standards, were selected to prepare LF-polysaccharide complexes to improve the stability of lactoferrin. The results showed that LF interacted more strongly with polysaccharides and did not affect the LF structure to a large extent when the pH and protein/polysaccharide mass ratio were 7 and 10:1 for LF-CG, 8 and 5:1 for LF-XG, 7 and 15:1 for LF-LBG. The zeta potential and fluorescence intensity of the LF-polysaccharide complexes displayed a decreasing trend with the increase in pH. When pH < 6, LF-CG and LF-XG exhibited precipitation and increased UV absorbance. Complexation between LF and CG/XG mainly attributed to electrostatic interactions, while LF and LBG form complexes based on hydrogen bonding or hydrophobic interactions. This study could provide a reference for the practical application of LF in infant formula. [Display omitted] • Complexation of LF and polysaccharide was used to enhance the stability of LF • Complexes were stable at pH 7–8 and W /W of 5:1 (LF-XG), 10:1 (LF-CG), 15:1 (LF-LBG) • Microfluidization promoted the formation of stable LF-polysaccharide complexes • Complexation between LF and CG/XG mainly attributed to electrostatic interactions • LF and LBG form complexes based on hydrogen bonding or hydrophobic interactions [ABSTRACT FROM AUTHOR]

This study aimed to develop complex coacervates utilizing lactoferrin (LF) and chia seed mucilage (CSM) for promoting intestinal delivery of quercetin (Q) and fortification of set yogurt. Three cross-linkers, including calcium chloride (CC), transglutaminase (TG), and polyphenolic complex (HP), were used to further reinforce the coacervate network. Cross-linked coacervates had higher values of coacervate yield, encapsulation efficiency, and loading capacity. They efficiently preserved Q under gastric condition (⁓87%–99%), with CSM-TG-Q-LF being most effective for intestinal delivery of Q. Moreover, digested pellets of the cross-linked coacervates displayed better antioxidant activity than the uncross-linked coacervates with CSM-TG-Q-LF pellets showing maximum bioactivity. The Q-loaded coacervates demonstrated superior assembly in the yogurt matrix compared to the unencapsulated Q. Moreover, the coacervate systems, especially CSM-TG-Q-LF significantly improved the textural properties of yogurt and the stability of Q in it. Therefore, CSM-TG-LF is a promising carrier to promote intestinal delivery and food application of hydrophobic molecules. [Display omitted] • Complex coacervates were formed using lactoferrin (LF) and chia seed mucilage (CSM) • Crosslinkers improved the coacervation process and encapsulation efficiency • Coacervation enhanced the solubility & gastrointestinal stability of quercetin (Q) • CSM-TG-Q-LF was superior in intestinal delivery of Q with enhanced bioactivity • Complex coacervates, especially CSM-TG-Q-LF, improved the texture of set yogurt [ABSTRACT FROM AUTHOR]

This study explored the impact of homogenization (at pressures of 16, 30, and 45 MPa) on both raw and high hydrostatic pressure (HHP)-treated human milk (HM). It focused on protein compositions and binding forces of soluble and insoluble fractions for both milk fat globule membrane (MFGM) and skim milk. Mild homogenization of HHP-treated milk increased lactoferrin (LF) levels in the insoluble fractions of both MFGM and skim milk, due to insoluble aggregation through hydrophobic interactions. Intense homogenization of HHP-treated milk decreased the LF level in the MFGM fractions due to the LF desorption from the MFGM, which increased LF level in the insoluble skim milk fraction. Homogenized-HHP treated milk showed noticeably higher casein (CN) level at the MFGM compared to homogenized-raw milk, attributed to HHP effect on CN micelles. Overall, the combined use of HHP and shear-homogenization should be avoided as it increased the biological proteins in insoluble fractions. • Homogenization of raw milk enhanced insoluble lactoferrin at fat globule membrane. • Pre-pressurization enhanced casein at fat globule membrane in post-homogenized milk. • Mild homogenization of pressurized milk insolubilized lactoferrin at the fat surface. • Mild homogenization of pressurized milk enhanced insoluble lactoferrin in skim milk. • Intense homogenization of pressurized milk desorbed lactoferrin from the fat surface. [ABSTRACT FROM AUTHOR]

Studies have suggested that milk may enhance or neutralize the bioavailability of coffee polyphenols, possibly due to reversible and irreversible interactions between coffee polyphenols and milk proteins. The effects of non-covalent and covalent binding of lactoferrin (BLF) to caffeic acid (CAA) on protein structure and function were investigated. SDS-PAGE analysis confirmed the covalent interaction between BLF and CAA. Multispectral experiments characterized the BLF-CAA complexes and conjugates, revealing alterations in the tertiary structure of the proteins in the BLF-CAA conjugates. Molecular docking and kinetics results demonstrated that hydrogen bonding, electrostatic interaction, and hydrophobic forces were the primary internal forces between CAA and BLF. When combined with CAA, the covalent conjugates exhibited superior functional properties including solubility, oxidation resistance, thermal stability, emulsification and foamability, bioaccessibility, and antimicrobial properties. This study offers a theoretical foundation and technical benchmark for the preparation of protein-based delivery vectors with synergistic effects. • Non-covalent and covalent conjugation of lactoferrin with caffeic acid were compared. • Conjugates were synthesized using laccase-catalyzed oxidation, free radical grafting, and base treatment. • The binding force of lactoferrin to caffeic acid was predicted using molecular docking and MD. • The covalent conjugates exhibited superior functional properties. [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]

Lactoferrin (LF) with various biological functions demonstrates great application potential. However, its application was restricted by its poor gelation and instability. The aim of this work was to explore the effect of microbial transglutaminase (MTGase) and Tremella fuciformis polysaccharide (TP) on the functional properties of LF. The formation of a self-supporting LF gel could be induced by MTGase through generating covalent crosslinks between the LF protein molecules. Meanwhile, TP was introduced into the gel system to improve the strength of LF-TP composite gels by enhancing non-covalent interactions such as hydrogen bond and electrostatic interactions during gel formation. Additionally, the LF-TP composite gel exhibited outstanding functional characteristics such as gastrointestinal digestive stability and antioxidant property. This work clarified the mechanism on MTGase and TP-mediated modification of lactoferrin, offered a novel strategy to increase the functional characteristics of LF, and enlarged the application range of LF and TP. [Display omitted] • LF could form gels by MTGase induction. • TP had a significant effect on the gel properties of MTGase-induced LF gel. • Covalent and hydrogen bonds interactions played major roles in LF-TP composite gel. • LF-TP composite gel demonstrated excellent mechanical and antioxidant properties. • LF-TP composite gel showed effective protection against Cur by in vitro digestion. [ABSTRACT FROM AUTHOR]

Colostrum refers to the initial milk that mammals generate following childbirth, and it possesses rich nutritional value. Due to its bioactive components (such as lactoferrin, lactoperoxidase, and immunoglobulins), colostrum actively contributes to various positive immune functions and specific cellular processes within the consumer's body. In clinical applications, research has shown that the immunoglobulins found in colostrum support the immune system, playing key roles in cell growth and development. Growth factors also contribute to various processes, including wound healing and metabolic functions. Lactoferrin and lactoperoxidase support the body's immunity, while another bioactive component, functional oligosaccharides, selectively promote growth in the microbiome. Additionally, nucleotide monophosphates play crucial roles in numerous vital physiological functions, including the synthesis of proteins, lipids, and carbohydrates. The supplementation of colostrum has shown promising results in combating various diseases caused by different pathogens, such as gastrointestinal infections, diarrhea, gut-barrier diseases, and inflammatory bowel disease. Based on reports of these clinical applications, the effects of colostrum against various diseases have been observed. Further research may reveal different therapeutic effects of colostrum on different diseases. By exploring the clinical applications of colostrum supplementation and the mechanisms of action of its bioactive components against specific diseases, this review highlights the potential of colostrum as a therapeutic agent and provides insights into its multifaceted effects. [ABSTRACT FROM AUTHOR]

Sodium alginate hydrogel beads and sodium alginate/gellan gum composite hydrogel beads crosslinked by calcium chloride were prepared with different alginate concentrations (3–20 mg·mL−1). Additionally, a simple method for growing CaCO 3 in situ on the hydrogel to create novel inorganic-organic hybrid hydrogel beads was presented. FT-IR analysis revealed the involvement of hydrogen bonding and electrostatic interactions in bead formation. Swelling behavior in acidic conditions showed a maximum of 13 g/g for composite hydrogels and CaCO 3 -incorporated hybrid hydrogels. Lactoferrin encapsulation efficiency within these hydrogels ranged from 44.9 to 56.6%. In vitro release experiments demonstrated that these hydrogel beads withstand harsh gastric environments with <16% cumulative release of lactoferrin, achieving controlled release in intestinal surroundings. While composite sodium alginate/gellan gum beads exhibited slower gastrointestinal lactoferrin digestion, facile synthesis and pH responsiveness of CaCO 3 -incorporated hybrid hydrogel also provide new possibilities for future studies to construct a novel inorganic-organic synergetic system for intestinal-specific oral delivery. • Developing polysaccharide hydrogel beads crosslinked by calcium chloride. • A facile synthesis strategy for the growth of CaCO 3 in situ on the hydrogel. • Expanding the application of CaCO 3 particles as carriers in oral delivery. • Providing new possibilities for lactoferrin oral delivery. [ABSTRACT FROM AUTHOR]

Background Deoxynivalenol (DON) is a major mycotoxin present in staple foods (particularly in cereal products) that induces intestinal inflammation and disrupts intestinal integrity. Lactoferrin (LF) is a multifunctional protein that contributes to maintaining intestinal homeostasis and improving host health. However, the protective effects of LF on DON-induced intestinal dysfunction remain unclear. Objectives This study aimed to investigate the effects of LF on DON-induced intestinal dysfunction in mice, and its underlying protective mechanism. Methods Male BALB/c mice (5 wk old) with similar body weights were divided into 4 groups (n  = 6/group) and treated as follows for 5 wk: Veh [peroral vehicle daily, commercial (C) diet]; LF (peroral 10 mg LF/d, C diet); DON (Veh, C diet containing 12 mg DON/kg); and LF + DON (peroral 10 mg LF/d, DON diet). Intestinal morphology, tight junction proteins, cytokines, and microbial community were determined. Data were analyzed by 2-factor ANOVA or Kruskal–Wallis test. Results The DON group exhibited lower final body weight (−12%), jejunal villus height (VH; −41%), and jejunal occludin expression (−36%), and higher plasma IL-1β concentration (+85%) and jejunal Il1b mRNA expression (+98%) compared with the Veh group (P  < 0.05). In contrast, final body weight (+19%), jejunal VH (+49%), jejunal occludin (+53%), and intelectin 1 protein expression (+159%) were greater in LF + DON compared with DON (P  < 0.05). Additionally, jejunal Il1b mRNA expression (−31%) and phosphorylation of p38 and extracellular signal regulated kinase 1/2 (−40% and − 38%) were lower in LF + DON compared with DON (P  < 0.05). Furthermore, the relative abundance of Clostridium XIVa (+181%) and colonic butyrate concentration (+53%) were greater in LF + DON compared with DON (P  < 0.05). Conclusions Our study highlights a promising antimycotoxin approach using LF to alleviate DON-induced intestinal dysfunction by modulating the mitogen-activated protein kinase pathway and gut microbial community in mice. [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]

A substantial disease burden in vertebrates is due to Gram-negative bacteria that exclusively inhabit the upper respiratory or genitourinary tracts of their hosts and rely on directly acquiring iron from the host iron-binding glycoproteins through surface receptor proteins. The receptors enable these bacteria to proliferate independently from their neighbors on the mucosal surface and during invasive infection of the host. The diversity in these receptors evolved over millions of years of evolution, which thus bodes well for long-lasting vaccine coverage. Experiments in food production animals provide proof of concept for the use of engineered antigens derived from the receptor proteins to prevent colonization and invasive infection in the natural host, strongly supporting development of these vaccines for use in humans. The presence of transferrin (Tf) receptors in Gram-negative bacteria that reside in the upper respiratory tract of mammals and birds indicate that they have existed for over 320 million years. Tf/lactoferrin receptors are essential for survival of Gram-negative bacterial pathogens (pathobionts) on the mucosal surface and during invasive infection and thus are ideal targets for vaccines. Structure-based antigen engineering can improve the immune response induced by Tf receptor proteins. Proof of concept experiments in pigs demonstrate that antigens targeting Tf receptors can prevent infection and colonization. [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf) is an iron-binding glycoprotein with potentially beneficial biological functions. However, the interaction between Lf and type 2 diabetes mellitus (T2DM) remains unclear. We hypothesized that Lf would improve hepatic insulin resistance and pancreatic dysfunction in diabetic mice. Male C57BL/6J mice were fed a high-fat diet for 15 weeks and injected with streptozotocin (STZ) for 5 consecutive days to establish a T2DM model. One week after STZ injection, mice with ≥11.1 mmol/L fasting blood glucose concentration were considered T2DM mice. These mice received 0.5% or 2% Lf solution for another 12 weeks. Biochemical parameters were measured, and histopathological examination of the pancreas and liver was performed. Hepatic protein expression related to the insulin signalling pathway was also assessed. Diabetic mice showed insulin resistance and abnormal glucolipid metabolism. Lf decreased serum concentrations of glycated serum protein, fasting insulin, cholesterol, and triglyceride and increased liver insulin sensitivity. Hematoxylin-eosin staining showed that Lf reversed the abnormal pancreatic islets of diabetic mice. Lf improved pancreatic dysfunction by reducing oxidative stress and inflammation responses. Furthermore, Lf upregulated the protein expression of insulin receptor, insulin receptor substrate-1, glucose transporter 4, phosphor phosphatidylinositol 3-kinase/phosphatidylinositol 3-kinase (PI3K), and phosphor protein kinase B/protein kinase B (AKT) in the liver. This study indicated that Lf supplementation improved hepatic insulin resistance and pancreatic dysfunction, possibly by regulating the PI3K/AKT signaling pathway in T2DM mice. Mice were fed with a high-fat diet for 15 weeks and injected with streptozotocin for 5 consecutive days to establish a type 2 diabetes mellitus model. Diabetic mice received 0.5% or 2% Lf solution for another 12 weeks. Lf treatment decreased glycated serum protein, insulin, and lipids. Lf also improved pancreatic dysfunctions by reducing oxidative stress and inflammation responses in serum and pancreas. Lf increased liver insulin sensitivity and upregulated the protein expression related to the insulin signal pathway and PI3K/AKT signaling pathway in the liver. Thus, Lf improved hepatic insulin resistance and pancreatic dysfunctions in diabetic mice. [Display omitted] [ABSTRACT FROM AUTHOR]

Infant intestinal development is immature and, thus, is vulnerable to bacterial and viral infections, which damage intestinal development and even induce acute enteritis. Numerous studies have investigated that lactoferrin (LF) has protective effects on the intestine and may play a role in preventing intestinal inflammation in infants. Lactoferrin is divided into 2 types, namely apo-LF and holo-LF, depending on the degree of iron saturation, which may affect its bioactivities. However, the role of LF iron saturation in protecting infant intestinal inflammation has not been clearly clarified. Therefore, in this study, young mice models with intestinal damage induced by lipopolysaccharides (LPS) in vivo and primary intestinal epithelial cells in vitro were constructed to enteritis injury in infants for investigation. The apo-LF and holo-LF were subsequently applied to the mouse models to investigate and compare their levels of protection in the intestinal inflammatory injury, as well as to identify which LF was most active. Moreover, the specific mechanism of the LF with optimal iron saturation was further investigated through Western blot assay. Results demonstrated that disease activity index, shortened length of colon tissue, and histopathological score were significantly decreased in the apo-LF group compared with those of the LPS group and the holo-LF group. In the apo-LF group, the concentration of LPS in the intestinal tract and the number of gram-negative bacteria colonies decreased significantly and the expression levels of proinflammatory factors in the colon tissue were downregulated, in comparison with those in the LPS group. The findings of this study thus verify that apo-LF can significantly alleviate enteritis injury caused by LPS, through regulating the PPAR-γ/PFKFB3/NF-κB inflammatory pathway. [ABSTRACT FROM AUTHOR]

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]

Parkinson's disease (PD) is a debilitating neurodegenerative condition characterized by the loss of dopaminergic neurons within the substantia nigra. The specific molecular mechanisms through which PD-associated neuronal loss occurs remain unclear, and there is no available effective treatment against PD-related neurodegeneration. Resveratrol (RSV) has exhibited promising neuroprotective effects via antioxidant and anti-inflammatory activity. However, its poor bioavailability in the brain represents a challenge for its application in PD treatment. In this study, we synthesized RSV-loaded PLGA nanoparticles (RSV-PLGA-NPs) conjugated with lactoferrin (Lf) to enhance RSV diffusion into the brain and assessed whether this formulation improved the neuroprotective effects of RSV in experimental PD models. The Lf-conjugated RSV-PLGA-NPs (Lf-RSV-PLGA-NPs) exhibited enhanced internalization into SH-SY5Y and human brain microvascular endothelial cells as compared to RSV-PLGA-NPs and free RSV. Further, Lf-RSV-PLGA-NPs were more effective than RSV-PLGA-NPs and free RSV in attenuating the MPP+-induced generation of reactive oxygen species, reduction of mitochondrial membrane potential, and cell death. Importantly, Lf conjugation specifically increased the accumulation of RSV-PLGA-NPs in the brain as determined via bioluminescent imaging analyses. Our formulation substantially enhanced the neuroprotective effects of RSV in the MPTP-induced PD model. Hence, Lf-RSV-PLGA-NPs represent a promising tool for improving RSV bioavailability and neuroprotection within the brain. [Display omitted] • Resveratrol (RSV) has potent antioxidant and anti-inflammatory activities. • Lf-RSV-PLGA-NPs enhanced the brain permeability and brain distribution of RSV. • Lf-RSV-PLGA-NPs restored the dopamine and DOPAC levels in the striatum. • Lf-RSV-PLGA-NPs attenuated the activation of microglia and astrocytes. • Lf-RSV-PLGA-NPs reduced the level of proinflammatory cytokines in the PD mice model. [ABSTRACT FROM AUTHOR]

Human breast milk contains a rich array of bioactive substances, such as immunoglobulins, lactoferrin antimicrobial peptides, and glycerol monolaurate, which play a crucial role in providing immune protection to infants. Infant formula manufacturers strive to match mother's milk's nutritional makeup, including immune-boosting ingredients. Lactoferrin and glycerol monolaurate (GML) are important antibacterial compounds in human milk. The study aimed to investigate the effect of bovine lactoferrin (bLf) and GML in preventing the growth of inoculated bacteria into infant formula. The study examined both individual and combined use of these components. The bacteria that were tested included: 1) Gram-negative bacteria: Cronobacter sakazakii strains 12868 and 29004, Pseudomonas aeruginosa , Salmonella enterica Typhimurium, and 2) Gram-positive bacteria: Methicillin-resistant Staphylococcus aureus (MRSA), and Listeria monocytogenes. The result of the agar diffusion assays showed that bLf, at a concentration of 16 mg/disc, exhibited strong inhibition (≥20 mm) of all the selected bacterial strains. On the other hand, GML at a concentration of 8 mg/disc showed strong inhibition of all strains; however, Gram-positive bacteria were more susceptible, so a concentration of 5 mg/disc was enough to achieve strong inhibition of these strains. The minimal bactericidal concentrations (MBC) analysis aimed to achieve a >3-log reduction in the growth of various bacterial strains. The results showed that S. enterica Typhimurium and L. monocytogenes were more susceptible to bLf than the other strains (MBC: 7 and 4.8 mg/ml, respectively, vs. 14.9–18.4 mg/ml for the other strains). In contrast, MRSA and L. monocytogenes were more susceptible to GML (MBC: 6 and 10 mg/ml, respectively, vs. 16–18 mg/ml for Gram-negative strains). The results of reconstituted powdered infant formulas (RPIF), with the addition of bLf, GML, or both at pathogen-specific MBC, showed significant log reductions in the growth of experimentally inoculated bacteria compared to the control at different time intervals. All bacterial strains exposed to bLf and GML exhibited >3-log reduction within 72 h, with Gram-positive strains showing >7-log reduction. GML and bLf combined had a stronger anti-bacterial activity than individual components, indicating the potential of combining GML and bLf as natural agents against specific pathogenic bacteria. Future studies are needed to understand the potential use of these compounds in different food matrices and clinical settings. • Antimicrobial effect was studied for lactoferrin and glycerol monolaurate. • Inactivation was observed on Gram-positive and Gram-negative pathogenic bacteria. • Mitigation against foodborne pathogens in infant formula. [ABSTRACT FROM AUTHOR]

Among the numerous biofunctional properties of lactoferrin, its ability to bind iron ions can be considered a core function. The saturation level with ferric iron affects the stability and functionality of the protein. To reliably quantify the iron saturation, an assay based on the color reagent Ferrozine was developed and validated concerning the lower detection (0.023 μg mL−1) and quantification limits (0.069 μg mL−1), as well as precision, recovery and accuracy values. The established assay was used to monitor iron uptake, comparing two commercially available bovine lactoferrin powders. Significant differences between the samples were observed. One sample exhibited nearly ideal binding behavior with a high affinity for ferric iron (saturation > 98 %), while the comparison sample did not exceed saturation values >80 %. This finding underscores the importance of assessing the iron status and binding capacity for the quality evaluation of lactoferrin products. • Quantitative determination of bound iron in lactoferrin by colorimetric ferrozine assay. • Validation of the assay concerning limits, precision, accuracy and recovery. • Lactoferrin from different manufacturers showed significant deviations in the total iron binding capacity. [ABSTRACT FROM AUTHOR]

Variations in cheese quality are explained by many factors. Among them, some influence the microbiota of cheeses such as native milk antimicrobial proteins. This project aimed to determine the concentration and activity of lactoferrin (LF), lactoperoxidase (LP) and lysozyme (LZ) during cheesemaking. Each antimicrobial protein was analyzed by two methods. An enzyme-linked immunosorbent assay (ELISA) technique was utilized to analyze each antimicrobial protein. In addition, LP was measured by spectrometry and LZ by fluorescence. Despite the lack of correlation between the results obtained by ELISA and the other methods, the measurement of LF, LP and LZ in raw milk and thermized milk showed no significant differences. The ELISA methods were selected to determine the retention of LF, LP and LZ in fresh cheese made from thermized milk. A total of 12 independent assays of cheddar cheese made commercially by a Canadian Dairy processor and at a pilot plant were evaluated. The concentration and activity of the three antimicrobial proteins were higher in cheese than in milk by an average factor of 3.5. These results allow a better understanding of the transition of the antimicrobial proteins present in milk when making cheese and to potentially, be able to control their concentration. • Lysozyme, lactoperoxidase and lactoferrin level were evaluated in milk and cheese. • ELISA methods was suitable to evaluate the antimicrobial protein levels. • All antimicrobial proteins were stable to thermization heat process. • All antimicrobial proteins were retained in Cheddar cheese. [ABSTRACT FROM AUTHOR]

The study explores the inhibitory potential of bioactive peptides from lactoferrin (LF), a versatile milk glycoprotein derived from bovine and human milk, against angiotensin-converting enzyme (ACE) and dipeptidyl peptidase-IV (DPP-IV). Firstly, in silico digested LF sequences were screened for potential ACE and DPP-IV inhibitory activity using AHTpin and StackDPPIV, respectively. Molecular docking showed that bovine LF peptides, "EPYF" (−10.1 kcal mol−1) and "WQWR" (−9.3 kcal mol−1), had significantly lower binding energies with ACE and DPP-IV, respectively. In addition, in vitro analysis of bovine LF hydrolysates displayed an IC50 value of 0.48 ± 0.01 (ACE) and 0.93 ± 0.02 mg mL−1 (DPP-IV). Liquid chromatography-mass spectrometry (LC-MS/MS) analysis identified ACE and DPP-IV inhibitory peptides, "EPYF" and "WQWR", which were present within the parent peptide sequences of the bovine LF hydrolysates. Considering the potential bioactivities of bovine LF peptides and their functional similarities with human LF, bovine LF could be exploited as a promising alternative to human LF. • First report confirming lactoferrin (LF) from bovine milk is a suitable alternative to human milk LF. • In silico pepsin-trypsin digestion (PTD) using BIOPEP generated 129 and 117 peptides for bovine and human LF, respectively. • Interactions between the LF peptides and ACE and DPP-IV enzyme are predominantly characterised by carbon hydrogen bonds. • LC-MS/MS confirmed the presence of "EPYF" and "WQWR" within the parent peptide sequences of the bovine LF hydrolysates. [ABSTRACT FROM AUTHOR]

High-pressure processing (HPP) of donor human milk (DM) minimally impacts the concentration and bioactivity of some important bioactive proteins including lactoferrin, and bile salt-stimulated lipase (BSSL) compared to Holder pasteurization (HoP), yet the impact of HPP and subsequent digestion on the full array of proteins detectable by proteomics remains unclear. We investigated how HPP impacts undigested proteins in DM post-processing and across digestion by proteomic analysis. Each pool of milk (n = 3) remained raw, or was treated by HPP (500 MPa, 10 min) or HoP (62.5 °C, 30 min), and underwent dynamic in vitro digestion simulating the preterm infant. In the meal, major proteins were minimally changed post-processing. HPP-treated milk proteins better resisted proximal digestion (except for immunoglobulins, jejunum 180 min) and the extent of undigested proteins after gastric digestion of major proteins in HPP-treated milk was more similar to raw (e.g., BSSL, lactoferrin, macrophage-receptor-1, CD14, complement-c3/c4, xanthine dehydrogenase) than HoP. • Study assessing how human milk pasteurization impacts protein digestion in vitro. • Pasteurization minimally changes proteins (count, abundance) pre-digestion. • Increased proteolysis in Holder vs. high-pressure milk during gastric phase. • Simulated digestion of raw and high-pressure milk yields similar profiles. • Key proteins in high-pressure milk better resist proximal digestion vs. Holder. [ABSTRACT FROM AUTHOR]

Fortification of human milk (HM) is often necessary to meet the nutritional requirements of preterm infants. The present experiment aimed to establish whether the supplementation of HM with either an experimental donkey milk-derived fortifier containing whole donkey milk proteins, or with a commercial bovine milk-derived fortifier containing hydrolyzed bovine whey proteins, affects peptide release differently during digestion. The experiment was conducted using an in vitro dynamic system designed to simulate the preterm infant's digestion followed by digesta analysis by means of LC-MS-MS. The different fortifiers did not appear to influence the cumulative intensity of HM peptides. Fortification had a differential impact on the release of either donkey or bovine bioactive peptides. Donkey milk peptides showed antioxidant/ACE inhibitory activities, while bovine peptides showed opioid, dipeptil- and propyl endo - peptidase inhibitory and antimicrobial activity. A slight delay in peptide release from human lactoferrin and α-lactalbumin was observed when HM was supplemented with donkey milk-derived fortifier. • Donkey milk and bovine milk fortifiers have a similar effect on human milk peptides • Peptides from donkey and human caseins represent the majority of digestion products • A delayed peptide release for some proteins is observed with donkey milk fortifier • Donkey milk fortification provides ACE inhibitory/antioxidant bioactive peptides [ABSTRACT FROM AUTHOR]

In this study, non-covalent binding mechanism of lactoferrin (LaF)-theaflavin (TF) complex and its functional properties were investigated. Multi-spectroscopic analyses showed that the secondary structure of LaF was altered with increasing TF concentration. The non-covalent binding of TF to LaF resulted in a reduction in the content of the α -helix and β -sheet, as well as a decrease in the fluorescence intensity of LaF. DSC result showed that non-covalent binding of TF improved thermal stability of LaF. Molecular dynamics simulations confirmed that the stable binding of LaF-TF was driven by hydrogen bonding and hydrophobic interactions. Additionally, non-covalent binding of TF increased the antioxidant capacity and emulsifying properties of LaF. Dynamic interfacial tension indicated that the strong interaction between LaF and TF reduced the interfacial tension, but improved the rheological properties of LaF. The functional characteristics of the non-covalent complex was effectively enhanced, paving the way for its potential use in the food industry. [Display omitted] • Interaction mechanism between lactoferrin (LaF) and theaflavin (TF) was elucidated. • Non-covalent binding of TF altered the secondary structure and functional properties of LaF. • Binding between LaF and TF was driven by hydrogen bonding and hydrophobic interaction. • Addition of TF improved the thermal stability, antioxidant capacity and emulsifying properties of LaF. • Non-covalent binding of TF to LaF reduces their interfacial tension and viscosity. [ABSTRACT FROM AUTHOR]

This study explored the relationship between the interfacial behavior of lactoferrin-(−)-epigallocatechin-3-gallate covalent complex (LF-EGCG) and the stability of high internal phase Pickering emulsions (HIPPEs). The formation of covalent bond between lactoferrin and polyphenol was verified by the increase in molecular weight. In LF-EGCG group, the surface hydrophobicity, interfacial pressure, and adsorption rate were decreased, while the molecular flexibility, interfacial film viscoelasticity, and interfacial protein content were increased. Meanwhile, LF-EGCG HIPPE possessed reduced droplet size, increased ζ-potential and stability. Rheology showed the viscoelasticity, structural recovery and gel strength of LF-EGCG HIPPE were improved, giving HIPPE inks better 3D printing integrity and clarity. Moreover, the free fatty acids (FFA) release of LF-EGCG HIPPE (62.6%) was higher than that of the oil group (50.1%). Therefore, covalent treatment effectively improved the interfacial properties of protein particles and the stability of HIPPEs. The macroscopic properties of HIPPEs were positively regulated by the interfacial properties of protein particles. The result suggested that the stability of emulsions can be improved by regulating the interfacial properties of particles. • Covalent treatment improved the interfacial properties of lactoferrin. • High internal phase Pickering emulsions (HIPPEs) combined with the covalent complex (LF-EGCG) increased stability. • HIPPEs stabilized with LF-EGCG had better rheological and 3D printing properties. • Lactoferrin-based particles stabilized HIPPEs across a wide pH range (pH 3.0–9.0). [ABSTRACT FROM AUTHOR]

Bovine leukemia virus (BLV) is a widespread virus that decreases milk production and quality in dairy cows. As crucial components of BLV, BLV-encoded microRNAs (BLV-miRNAs) affect BLV replication and may impact the synthesis of Lactoferrin (LTF), Lactoperoxidase (LPO), Alpha-lactalbumin (alpha-LA), and Beta-lactoglobulin (beta-LG). In this study, we investigated the targeting relationship between BLV-miRNAs and LTF, LPO, alpha-LA, and beta-LG in cow's milk. Additionally, we investigated the possible mechanisms by which BLV reduces milk quality. The results showed that cow's milk had significantly lower levels of LTF, LPO, and alpha-LA proteins in BLV-positive cows than in BLV-negative cows. BLV-△miRNAs (miRNA-deleted BLV) enhanced the reduction of LPO, alpha-LA, and beta-LG protein levels caused by BLV infection. Multiple BLV-miRNAs have binding sites with LTF and LPO mRNA; however, only BLV-miR-B1–5 P has a targeting relationship with LPO mRNA. The results revealed that BLV-miR-B1–5 P inhibits LPO protein expression by targeting LPO mRNA. However, BLV does not directly regulate the expression of LTF, alpha-LA, or beta-LG proteins through BLV-miRNAs. [Display omitted] • BLV inhibits the expression of LTF, LPO, alpha-LA and beta-LG proteins in cow's milk. • BLV-miR-B1–5 P inhibits LPO protein expression by targeting LPO mRNA. • BLV does not directly regulate the expression of LTF, alpha-LA, or beta-LG proteins through BLV-miRNAs. [ABSTRACT FROM AUTHOR]