Search Results (100)

Introduction: Candidozyma auris (Cz. auris) has emerged globally, and diseases caused by it are associated with a mortality rate of 30–72%. This yeast is often multidrug-resistant and challenging to treat. A synthetic peptide, consisting of 11 amino acids of human lactoferrin (hLF1-11), offers a new therapy that is active against Candida albicans, non-albicans Candida yeasts, as well as Cz. auris. The current study examined the susceptibility of clinically relevant Candida species to hLF(1-11) in vitro and investigated the synergistic interaction of this peptide with fluconazole (FLU) and anidulafungin (ANI). Methods: Susceptibility of the yeasts to hLF(1-11) was tested with a microdilution method to determine minimum inhibitory concentrations (MICs). A total of 59 strains belonging to 16 species of Candida or Candidozyma were tested. The treatment cohort included 20 strains of Cz. auris originating from six different countries. Results: Mean MIC values of all susceptible strains ranged from 16.66 ± 6.46 μg/mL to 45.83 ± 10.21 μg/mL. There were no statistical differences in the susceptibility of hLF(1-11) for Cz. auris across geographic origins. In the combinatory tests, drugs acting together, the fractional inhibitory concentration indexes [FIC] < 1.0, showed a synergistic or additive effect on the efficacy of FLU and ANI when used in combination with hLF(1-11). [FIC] indexes 1–2 were interpreted as intermediate. MIC values in combinatory use were 1–2 titer steps lower than when used alone. Conclusions: hLF(1-11) inhibits the growth of yeasts that belong to the genus Candida, including Cz. auris. The combinatory use may be further investigated to treat infections caused by resistant yeasts. Full article

Cardiovascular disease (CVD) remains a leading cause of mortality worldwide, with dyslipidemia, obesity, diabetes mellitus, and hypertension being major modifiable risk factors. Functional foods with antioxidant and anti-inflammatory properties have gained attention for their potential for reducing CVD risk. Edible bird’s nest (EBN), a functional food rich in bioactive compounds such as sialic acid, lactoferrin, and glycoproteins, has been shown to exhibit antioxidant and anti-inflammatory effects. This review explores the potential of EBN in mitigating CVD risk factors, focusing on its role in improving lipid profiles, managing obesity, and enhancing glucose metabolism. EBN has been shown to improve the lipid profile by regulating the hepatic cholesterol metabolism and gut–liver axis interactions. Additionally, EBN reduces body weight gain and visceral fat accumulation, improves adipokine regulation, and enhances insulin sensitivity, which may collectively support cardiovascular health. Despite promising findings, clinical evidence remains limited. Future research should focus on clinical trials to validate its efficacy, determine optimal dosages, and assess its long-term safety. Additionally, further studies on EBN’s effects on hypertension and its interaction with conventional therapies could enhance its potential role in CVD prevention and management. Full article

Background: Lactoferrin is a major functional protein involved in maintaining human health, which possesses antioxidant, anti-inflammatory, antibacterial, and antiviral properties. Therefore, it can be used to support the treatment of viral and bacterial diseases, as well as in cancer prevention. Lactoferrin-manufacturing processes may compromise its protein structure and function, so it is necessary to establish reliable analytical methods for production efficiency and quality control purposes. This paper reviews the lactoferrin production processes, summarising the methods using various matrices (milk, milk powder, infant formula, whey, bovine lactoferrin lyophilised powder, yoghurt, colostrum, and human milk), the most popular purification methods, and sample preparation. Material and methods: The Medline and Embase databases were searched using the following phrases: ”lactoferrin” and “purification” or “isolation” or “extraction” or “separation”. The search was limited to recent studies from the last five years published in English up until 12 March 2025. Of the 573 articles identified, 17 were reviewed. Results: Lactoferrin purification and determination methods depend on the matrix used. The latest research focuses on improving parameters of lactoferrin determination, shortening time, improving efficiency or limiting costs, and even reducing toxicity by changing the reagents. The method of separating lactoferrin using magnetic beads or nanoparticles has been developed, as well as the determination parameters using high-performance liquid chromatography (HPLC). Conclusions: The current lactoferrin production techniques are characterised by increased efficiency and quality, but they require standardisation of the purification process depending on the matrix. The latest Lf determination methods are highly precise, and most of them produce high-quality Lf. This allows to introduce on the market a higher quality product, which can significantly improve standard approaches. Full article

Three novel endo-β-N-acetylglucosaminidases (AVUL01, BCAC01, and BFIN01) classified as members of the glucoside hydrolase (GH) family 18 were identified from human fecal samples and then cloned and characterized for their ability to hydrolyze two distinct classes of N-glycans. Endo-β-N-acetylglucosaminidases (ENGases) are known for the hydrolysis of chitin and the N,N′-diacetylchitobiose core of N-linked glycans, depending on the glycan architecture. N-glycans have shown bioactivity as substrates in the human gut microbiome for microbes that encode ENGases, thus demonstrating their ecological relevance in the gut. However, distinct types of N-glycan structures, for example, oligomannosidic or complex, have been shown to enrich different microbes within the human gut. Novel advances in food technology have commercialized animal-derived dietary proteins with oligomannosidic instead of traditionally complex N-glycans using precision fermentation. This indicates that there is an unmet need to identify the classes of N-glycans that gut-derived ENGases act upon to determine whether these novel proteins alter gut ecology. AVUL01, BCAC01, and BFIN01 all demonstrated activity on exclusively oligomannosidic N-glycans from RNase B and bovine lactoferrin; however, they failed to show activity on complex or α-1,3-core fucosylated high-mannose N-glycans derived from fetuin and horseradish peroxidase, respectively. These results suggest that α-1,3 core fucosylation and complex N-glycan architecture inhibit the activity of AVUL01, BCAC01, and BFIN01. Furthermore, BFIN01 performed significantly better than BCAC01, resulting in a greater amount of N-glycans, suggesting that certain ENGases may possess enhanced specificity and kinetics as an evolutionary strategy to compete for resources. Full article

Background/Objectives: Lactoferrin, a protein involved in the immune response, plays a significant role in the etiopathogenesis of periodontitis in the general population. This cross-sectional study aims to determine the salivary concentration of lactoferrin in Down syndrome individuals with periodontitis. Methods: A convenience cohort of 76 Down syndrome individuals was established, including 34 with periodontitis, 29 with gingivitis, and 13 with healthy gums. Unstimulated saliva samples were collected and processed to quantify the lactoferrin concentration using the Human Lactoferrin ELISA kit, the total protein concentration (bicinchoninic acid assay [BCA]) using the BCA Protein Assay Kit (Pierce, Rockford, IL, USA), and the lactoferrin/BCA ratio. Additionally, the Lf rs1126478 (140A/G in exon 2, Lys/Arg) genotypes were determined via PCR with restriction fragment length polymorphism (RFLP) analysis using the Earl enzyme. Results: The lactoferrin levels were comparable across patients with periodontitis, gingivitis, and healthy gums (median = 8.20, 6.57, and 7.61 µg/mL, respectively). There were no differences in the BCA levels between the three groups (median = 2.21, 3.17, and 2.08 µg/µL, respectively) nor in the lactoferrin/BCA ratios. The distribution of the Lf 140A/G polymorphism did not show differences concerning periodontal health status. Conclusions: In Down syndrome individuals, salivary lactoferrin and BCA levels are not influenced by the periodontal health condition. Additionally, no significant genetic associations were found with the rs1126478 polymorphism in Down syndrome individuals with and without periodontitis. Lactoferrin production in Down syndrome may not be upregulated in response to periodontal pathogens, which could be indicative of an immune system dysregulation contributing to the early onset and severity of periodontitis in this population. Full article

Ear reconstruction surgeries for congenital deformities and trauma are common, highlighting the need for improved cartilage regeneration. Lactoferrin (LF), a natural and cost-effective protein, is promising due to its anti-inflammatory, antimicrobial, and prochondrogenic properties. This study investigates the effects of LF on the viability, proliferation, and chondrogenesis of rabbit auricular chondrocytes. For in vitro studies, auricular chondrocytes were cultured for three passages, after which 3D pellets were formed. LF significantly increased chondrocyte metabolic activity by 1.5 times at doses of 10 and 500 μg/mL. At passage 3, LF at concentrations of 10 and 100 μg/mL increased cell proliferation rates by 2- and 1.5-fold, respectively. Immunohistochemical staining of the pellets demonstrated that LF at 10 μg/mL increased the amount of sex-determining region Y-Box Transcription Factor 9 (Sox9)+ cells by 30%, while at 100 μg/mL, it doubled the type II collagen deposits. For in vivo studies, a rabbit ear defect model was utilized. On post-operative day 60, the LF-treated group exhibited more mature cartilage regeneration, with a higher density of elastic fibers. By day 90 post-surgery, LF application led to the restoration of normal elastic cartilage throughout the defect. These findings suggest that LF promotes auricular chondrocytes chondrogenesis and could be beneficial for tissue engineering of the elastic cartilage. Full article

Bio-based polymeric stimuli-responsive materials have attracted increasing interest, especially in the pharmacological and nutraceutical fields. These materials mainly consist of macromolecules capable of conformational and chemical changes in response to external signals. One active molecule mostly used in bio-related areas is lactoferrin (Lf), which is attracting attention due to its beneficial effects (antimicrobial, anti-inflammatory, and anti-carcinogenic) on the human body. Since pH or temperature in the human body can promote Lf degradation, encapsulation in a suitable system is required. A valid solution is to encapsulate the Lf in a polysaccharidic matrix such as alginate (ALG) thanks to its biocompatibility and easy gelation with bivalent cations. This work aims to encapsulate iron-depleted Lf in alginate gel microspheres for stability improvement by ionic cross-linking with Ca²⁺ ions. The obtained particles were characterized in terms of structure, thermal stability, and morphology, and their swelling capability was determined. Release studies were carried out on the freeze-dried particles to investigate the effect of neutral pH 7 and acidic pH 5. At last, the optimization of the loaded system was completed by developing a mathematical model able to predict the swelling behavior of the carrier particle and the subsequent Lf kinetic release over time. Full article

Goat milk has gained recognition for its medicinal, cosmetic, and health benefits, particularly its potential to improve human skin conditions. Its therapeutic properties are attributed to bioactive compounds influenced by genes such as lactoferrin (LTF), lysozyme (LYZ), and β-casein (CSN2), known for their antimicrobial, immunomodulatory, and anti-inflammatory effects. Genetic factors are hypothesized to shape goat milk’s composition and its effectiveness in managing dermatological conditions like eczema and psoriasis. Understanding these genetic determinants is critical to optimizing the use of goat milk in skin health applications. This review aims to explore the application of genomic tools to elucidate the medicinal properties of goat milk and its implications for skin care. By identifying the specific genes and molecular mechanisms underpinning its therapeutic effects, genomic studies have provided insights into the bioactive constituents of goat milk, such as peptides, proteins, and lipids, which contribute to its dermatological efficacy. Candidate genes, including growth hormone receptor (GHR), butyrophilin (BTN1A1), and lactoglobulin (LGB), have been identified as critical for enhancing milk quality and functionality. Future research should integrate genomic data with functional studies to further investigate goat milk’s immunomodulatory, antimicrobial, and antioxidant activities. Such insights could advance targeted breeding strategies and innovative formulations for managing inflammatory skin conditions and promoting skin health. Full article

Neurodegenerative diseases are characterized by progressive loss of neurons and persistent inflammation. Neurons are terminally differentiated cells, and lost neurons cannot be replaced since neurogenesis is restricted to only two neurogenic niches in the adult brain, whose neurogenic potential decreases with age. In this regard, the astrocytes reprogramming into neurons may represent a promising strategy for restoring the lost neurons and rebuilding neural circuits. To date, many anti-inflammatory agents have been shown to reduce neuroinflammation; however, their potential to restore neuronal loss was poorly investigated. This study investigates the anti-inflammatory effects of lactoferrin on DI-TNC1 astrocyte cell line and its ability to induce astrocyte reprogramming in a context of sustained inflammation. For this purpose, astrocytes were pre-treated with lactoferrin (4 μg/mL) for 24 h, then with lipopolysaccharide (LPS) (400 ng/mL), and examined 2, 9 and 16 days from treatment. The results demonstrate that lactoferrin attenuates astrocyte reactivity by reducing Toll-like receptor 4 (TLR4), Glial fibrillary acidic protein (GFAP) and IL-6 expression, as well as by upregulating Interleukin-10 (IL-10) cytokine and NRF2 expression. Moreover, lactoferrin promotes the reprogramming of reactive astrocytes into proliferative neuroblasts by inducing the overexpression of the Sex determining region Y/SRY-box 2 (SOX2) reprogramming transcription factor. Overall, this study highlights the potential effects of lactoferrin to attenuate neuroinflammation and improve neurogenesis, suggesting a future strategy for the treatment of neurodegenerative disorders. Full article

Background/Objectives: Lactoferrin (Lf), a multifunctional iron-binding protein, has considerable potential for use as an active ingredient in food supplements due to its numerous positive effects on health. As Lf is prone to degradation, we aimed to develop a formulation that would ensure sufficient stability of Lf in the gastrointestinal tract and during product storage. Methods: A simple, efficient, and well-established technology that has potential for industrial production was used for the double-coating of neutral pellet cores with an Lf layer and a protective enteric coating. Results: The encapsulation efficiency was 85%, which is among the highest compared to other reported Lf formulations. The results of the dissolution tests performed indicated effective protection of Lf from gastric digestion. A comprehensive stability study showed that the stability was similar regardless of the neutral pellet core used, while a significant influence of temperature, moisture, product composition, and packaging on the stability of Lf were observed, and were therefore considered in the development of the final product. The experimentally determined shelf life is extended from 15 to almost 30 months if the product is stored in a refrigerator instead of at room temperature, which ensures the commercial applicability of the product. Conclusion: We successfully transferred a technology commonly used for small molecules to a protein-containing product, effectively protected it from the destructive effects of gastric juice, and achieved an acceptable shelf life. Full article

Lactoferrin (LF) is an iron-binding glycoprotein of the transferrin family and has been suggested to have a variety of biological functions, including anticancer activity. However, the effects of LF and its mechanisms in anticancer therapies, especially in radiotherapy against cancer cells under hypoxic conditions, are not well-determined. In this study, we focused on the molecular mechanisms of LF functions in cells under hypoxic conditions. High-dose LF treatment showed cytotoxic activity in a variety of cells, including both non-cancer and cancer cells. Interestingly, hypoxic treatment increased the sensitivity to LF in some cancer cells but decreased it in non-cancer cells. LF treatment also altered sensitivity to radiation treatment: LF significantly increased the viability of irradiated KD non-cancer cells under hypoxic conditions but decreased that of HSC2 cancer cells. These effects were only observed when LF was treated within 3 h of irradiation, but not before irradiation. Importantly, knockdown of HIF1A counteracted these effects in both cell lines. Measurements of ROS activity showed that LF decreased ROS production in KD cells but increased it in HSC2 cells, resulting in a decrease in γH2AX foci in KD cells but an increase in HSC2 cells. RNA-seq and gene set enrichment analysis showed that LF treatment regulated gene expression related to the cell cycle, apoptosis, inflammation, and the NRF2 antioxidant signaling pathway. Quantitative RT-PCR confirmed the downregulation of the pro-apoptotic gene ASC in KD cells and the NRF2-regulated genes in HSC2 cells by LF treatment. Knockdown experiments confirmed the role of ASC in irradiated KD cells and NRF2 in irradiated HSC2 cells with LF treatment. In conclusion, lactoferrin was shown to affect radiation treatment by regulating apoptosis and NRF2 signaling in a cell type-specific manner under hypoxic conditions, suggesting its potential application as a protector or sensitizer for radiation therapy. Full article

In this study, an aptamer biosensor for detecting lactoferrin (LF) was developed using piezoelectric quartz-induced bond rupture sensing technology. The thiol-modified aptamer I was immobilized on the gold electrode surface of the quartz crystal microbalance (QCM) through an Au-S bond to specifically bind LF. It was then combined with aptamer–magnetic beads to amplify the mass signal. The peak excitation voltage was 8 V at the resonance frequency for the 60 MHz gold-plated quartz crystal. When the molecular bond cracking process occurred, the aptamer–magnetic beads combined on the surface of the piezoelectric quartz were removed, which resulted in an increase in quartz crystal resonance frequency. Therefore, the specific detection of LF can be realized. Under optimized experimental conditions, the linear range for LF was 10–500 ng/mL, the detection limit (3σ) was 8.2 ng/mL, and the sample recoveries for actual milk powder samples ranged from 97.2% to 106.0%. Compared with conventional QCM sensing technology, the signal acquisition process of this sensing method is simple, fast, and easy to operate. Full article

Background/Objectives: Injection of lipopolysaccharides (LPS) in experimental models induces a systemic inflammatory response that is associated with deleterious effects on intestinal morphology and physiology. In this study, we have studied in female mice the effects of dietary supplementation with bovine lactoferrin (bLF) given before intraperitoneal injection of LPS on jejunum and colon. Methods: The first study evaluated the efficiency of different bLF and LPS concentrations to determine the optimal experimental conditions. For the second study mice were fed with 1% bLF before the LPS challenge (3 mg/kg body weight). Plasmatic markers of inflammation, intestinal morphology, permeability, and expression of genes related to epithelial differentiation, epithelial barrier function and intestinal inflammation in both small intestine and colon were evaluated. Results: bLF ingestion before the LPS challenge reduced the TNF-α circulating concentration, compared to control animals. This decrease in plasma TNF-α was correlated with improved intestinal permeability. The morphology of jejunal epithelium, which was affected by LPS challenge, was partly maintained by bLF. Measurement of the expression of genes encoding proteins involved in epithelial differentiation, intestinal inflammation, and epithelial barrier function suggests an overall protective effect of bLF against the adverse effects of LPS in the jejunum. In the colon, the effects of bLF ingestion on the subsequent LPS challenge, although protective, remain different when compared with those observed on jejunum. Conclusions: Taken together, our data indicate that bLF dietary supplementation does have a protective effect on the deleterious intestinal alterations induced by LPS systemic inflammation. Full article

Objectives: The present study identified multiple proteins in early mature milk and explored the correlation between protein compositions in HM and maternal BMI during lactation. Methods: A total of 70 mothers giving birth to single-term infants from four representative cites were enrolled in this research. Milk samples were collected between 9 and 11 a.m. to avoid the influence of circadian rhythms. The concentration of total protein in the milk samples was determined using the Bradford method, and the concentrations of α-lactalbumin, lactoferrin, osteopontin, α_s−1 casein, β-casein, and κ-casein, butyrophilin, periodic acid Schiff 6/7, fatty acid-binding protein, and xanthine oxidoreductase in the milk samples were measured through a previously published method using ultra-performance liquid chromatography coupled with mass spectrometry. A semi-structured questionnaire investigation and body measurements were carried out by trained investigators to collect the information of subjects. Results: In the univariate models, the concentrations of TP (r = 0.306), α-La (r = 0.260), LF (r = 0.371), OPN (r = 0.286), and α_S1-CN (r = 0.324) were all positively and significantly correlated with maternal BMI. In the models’ adjusted covariates, the concentrations of TP (Lg β = 7.4 × 10⁻³), LF (Lg β = 19.2 × 10⁻³), α_S1-CN (Lg β = 8.2 × 10⁻³) and the proportion of LF (β = 0.20%) were positively correlated with continuous maternal BMI changes. TP concentrations in the HM of obese mothers were higher than in the other three groups (Lg β: 66.7 × 10⁻³~140.5 × 10⁻³), α-La concentrations were higher than in the underweight and normal groups (Lg β: 94.4 × 10⁻³~145.7 × 10⁻³), and OPN concentrations were higher than in the overweight groups (Lg β = 103.6 × 10⁻³). The concentrations of LF (Lg β: −298.2 × 10⁻³~−191.0 × 10⁻³), OPN (Lg β: −248.9 × 10⁻³~−145.3 × 10⁻³), and α_S1-CN (Lg β: −160.7 × 10⁻³~−108.3 × 10⁻³) in the HM of underweight mothers were lower than those in the other three groups. β-CN concentrations were lower than normal (Lg β = −125.1 × 10⁻³) and obese groups (Lg β = −165.7 × 10⁻³), κ-CN concentrations were lower than the overweight (Lg β = −132.5 × 10⁻³) and obese groups (Lg β = −147.9 × 10⁻³), and the proportion of LF was lower than that of the overweight (β = −2.80%) and obese groups (β = −2.52%). The proportion of LF in normal mothers was lower than that in the overweight group (β = −1.15%). No statistically significant associations between four MFGM proteins and maternal BMI were determined as the equation models could not be fitted (p for F-test < 0.05). Conclusions: Obese mothers had higher concentrations of multiple protein components than other groups, while underweight mothers had lower concentrations. The association between BMI and protein compositions may be more pronounced for certain protein types. Full article

Lactoferrin (LF) is a multifunctional protein abundant in breast milk that modulates the functions of neural stem cells. Recent studies have demonstrated the efficacy of bovine LF (bLF) in mitigating behavioral changes; however, the molecular mechanisms on the nervous system have not yet been elucidated. The presented study aimed to characterize the molecular mechanisms of bLF on nerve extension in PC12 cells. PC12 cells were treated with 0.01–1000 µg/mL of bLF, and cell viability was determined using the cell counting kit-8 assay after treatment for 24 h. Morphometric evaluation was performed after 24 or 72 h of treatment with 50 ng/mL nerve growth factor (NGF) or 100–500 µg/mL bLF. The molecular mechanisms were investigated using Western blotting and real-time quantitative PCR. Cell viability was significantly decreased after treatment with 600–1000 µg/mL bLF for 24 h compared with the control group. Morphometric evaluation revealed neurite outgrowth after 72 h of NGF treatment, with a significant increase in neurite outgrowth after treatment with 250 µg/mL bLF. The phosphorylated p44/42 expression ratio peaked at 5 min and persisted for up to 10 min. Quantitative real-time PCR revealed a significant decrease in MAP2 expression. Our findings suggested that bLF enhanced PC12 cell neurite outgrowth to a similar extent as NGF. These effects are thought to be mediated via the TrkA receptor and activated by the phosphorylated ERK signaling pathway. Therefore, this study demonstrates that bLF promotes neurite outgrowth via a pathway similar to that of NGF. Full article