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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]

The components of milk from beef cows remain to be elucidated. This study examined the differences in the antimicrobial components of milk between dairy and beef cows. Quarter milk was collected from both Japanese Black (beef type) and Holstein (dairy type) cows to compare the concentrations of antimicrobial components. The concentration of lingual antimicrobial peptide (LAP) was higher, whereas that of the other antimicrobial components (lactoferrin, S100A7, and S100A8) was lower in beef cows than in dairy cows. Overall, these results indicate that the differences in antimicrobial components between beef and dairy cows may be associated with the difference in the prevalence of mastitis between them. [ABSTRACT FROM AUTHOR]

Although the role of iron in bacterial infections has been well described for Staphylococcus (S.) aureus, iron acquisition in (bovine-associated) non-aureus staphylococci and mammaliicocci (NASM) remains insufficiently mapped. This study aimed at elucidating differences between four diverse bovine NASM field strains from two species, namely S. chromogenes and S. equorum, in regards to iron uptake (with ferritin and lactoferrin as an iron source) and siderophore production (staphyloferrin A and staphyloferrin B) by investigating the relationship between the genetic basis of iron acquisition through whole genome sequencing (WGS) with their observed phenotypic behavior. The four field strains were isolated in a previous study from composite cow milk (CCM) and bulk tank milk (BTM) in a Flemish dairy herd. Additionally, two well-studied S. chromogenes isolates originating from a persistent intramammary infection and from a teat apex were included for comparative purpose in all assays. Significant differences between species and strains were identified. In our phenotypical iron acquisition assay, while lactoferrin had no effect on growth recovery for all strains in iron deficient media, we found that ferritin served as an effective source for growth recovery in iron-deficient media for S. chromogenes CCM and BTM strains. This finding was further corroborated by analyzing potential ferritin iron acquisition genes using whole-genome sequencing data, which showed that all S. chromogenes strains contained hits for all three proposed ferritin reductive pathway genes. Furthermore, a qualitative assay indicated siderophore production by all strains, except for S. equorum. This lack of siderophore production in S. equorum was supported by a quantitative assay, which revealed significantly lower or negligible siderophore amounts compared to S. aureus and S. chromogenes. The WGS analysis showed that all tested strains, except for S. equorum, possessed complete staphyloferrin A (SA)-synthesis and export operons, which likely explains the phenotypic absence of siderophore production in S. equorum strains. While analyzing the staphyloferrin A and staphyloferrin B operon landscapes for all strains, we noticed some differences in the proteins responsible for iron acquisition between different species. However, within strains of the same species, the siderophore-related proteins remained conserved. Our findings contribute valuable insights into the genetic elements associated with bovine NASM pathogenesis. [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]

Copyright of Acta Stomatologica Naissi is the property of Clinic of Stomatology Nis and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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

Copyright of Cukurova Medical Journal / Çukurova Üniversitesi Tip Fakültesi Dergisi is the property of Cukurova University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Previous research has shown diminished nasal immune function following nasal saline irrigation (NSI), returning to baseline at 6 hours. The aim of this study was to examine the immune nasal proteome before and after 14 days of nasal irrigation. Methods: Seventeen healthy volunteers received either isotonic (IsoSal) or low salt (LowNa) NSI. Nasal secretions were collected before and 30 min after NSI at baseline and again after 14 days. Specimens were analyzed using mass spectrometry to detect proteins of relevance to nasal immune function. Results: One thousand eight hundred and sixty-five proteins were identified with significant changes in 71 proteins, of which 23 were identified as part of the innate immune system. Baseline analysis demonstrated an increase of 9 innate proteins after NSI, most after IsoSal. After 14 days, a greater increase in innate peptides was present, with most now in the LowNa group. When NSI solutions were compared, a significant increase in 4 innate proteins, including a 211% in lysozyme, was detected in the LowNa group. Conclusion: LowNa NSI demonstrates evidence of improving the innate immune secretions, especially lysozyme, in healthy volunteers. [ABSTRACT FROM AUTHOR]

Background. Anemia is a common nutritional problem in children, especially those under five. Lactoferrin (Lf) as a supplement in treating iron deficiency anemia (IDA) has been studied, but its results in children have not been reviewed. This review aims to evaluate the effect of lactoferrin on children with IDA. Methods. PubMed, ProQuest, EBSCO and Ovid databases were searched using a variation of keywords: lactoferrin, anemia, and children. The literature selected must be clinical trial-based in design. The years of the studies published were limited to 2012 and 2022. Results. Eleven studies were included in the final systematic review, consisting of 10 randomized controlled trials (RCTs) and 1 non-randomized trial. Serum ferritin (SF) and hemoglobin (Hb) were found to be increased in groups treated with Lf or a combination of Lf and elemental iron compared to iron only or placebo supplementation. Adverse events such as constipation, vomiting, anorexia, and abdominal pain were found; particularly, a significant decrease in constipation is seen in Lf-treated groups. Conclusions. This study supports Lf as a superior treatment for IDA in children regarding the improvement in hematological and iron indices and fewer adverse effects. [ABSTRACT FROM AUTHOR]

Endometriosis is a disease that is characterized by the ectopic presence of the endometrium or its similar cells. A high prevalence of patients with autoimmune diseases has been reported among patients with endometriosis although the cause of endometriosis remained unknown. Recently, the anti-lactoferrin antibody is reported to be highly detected in autoimmune diseases. This study focused on lactoferrin and anti-lactoferrin antibodies to explore the pathology of endometriosis. Lactoferrin is a substance that regulates inflammation and is produced by neutrophils. Anti-lactoferrin antibody is a type of perinuclear antineutrophil cytoplasmic antibody. The serum lactoferrin and anti-lactoferrin antibody levels were compared among patients with or without endometriosis, revealing significantly higher levels in patients with endometriosis. Additionally, a decreased serum anti-lactoferrin antibody level was observed after surgical endometriosis resection. The receiver operating characteristic curve analysis determined the reference values for the serum lactoferrin and anti-lactoferrin antibody levels. Patients whose serum level exceeded the reference anti-lactoferrin antibody value were significantly higher in more than 40% of cases in the endometriosis group. The rate is comparable to that of autoimmune diseases. This is the first report that anti-lactoferrin antibody is frequently observed in patients with endometriosis, adding a new perspective to the understanding of the pathology of endometriosis although precisely elucidating the mechanism by which lactoferrin and anti-lactoferrin antibody appear in endometriosis in the future is necessary. [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]

Amyloidosis is characterized by systemic or local deposition of amyloid fibrils outside organs and tissues. Amyloidosis is rarely seen on cornea. A 30-year-old woman patient had had trichiasis in both eyes for 8 years. Trichiasis was observed, which touched the cornea. Slit lamp microscopy showed white gelatinous droplet-like eminences and trichiasis in the lower cornea of the right eye. Optical coherence tomography showed that the lesion involved most of the cornea. Hematoxylin and eosin staining showed that most of the stroma stained red, with scattered inflammatory cells. High expression of lactoferrin was detected by mass spectrometry, and the case was diagnosed as secondary corneal lactoferrin amyloidosis in the right eye. [ABSTRACT FROM AUTHOR]

Introduction: People with lactose intolerance are suggested to consume dietary items containing less lactose, such as goat's milk. This study aimed to investigate the effects of goat's milk powder on the health of lactose intolerant middle-aged adults. Methods: A total of 60 subjects were recruited into this randomised controlled trial. They were divided into four groups and received different dietary interventions (goat's milk, goat's milk with curcumin, goat's milk with coffee, lactose-free milk) for five weeks. Health effects were compared between pre- and post-intervention. Anthropometric and biochemical parameters (blood glucose, insulin, lipid profile, C-reactive protein, and lactoferrin) were evaluated. Dietary intake was recorded using a food record. Results: Fifty-one lactose intolerant subjects completed the study. After ingestion of goat's milk, there were significant reductions in body fat (p=0.033) and a significant increase in the percentage of muscle (p=0.021). Waist circumference (WC) decreased in both the goat's milk with curcumin and goat's milk with coffee groups (p<0.05 for all). Unfortunately, high-density lipoprotein cholesterol (HDL-C) dropped after the five-week intervention in the goat's milk group (p=0.002). Lactoferrin level of the goat's milk group was higher than other groups at post-intervention (p<0.001). Besides, the goat's milk with coffee group seemed to consume more carbohydrates after completing the intervention (p=0.034). Conclusion: A five-week intake of goat's milk reduced the risk of abdominal obesity among middle-aged adults. In addition, it resulted in improved lactoferrin levels. [ABSTRACT FROM AUTHOR]

Lactoferrin is a member of the high affinity to glycoprotein family of transferrin for iron and plays a role in natural immunity as well as antibacterial, antifungal, antiviral, antiparasitic, antioxidant, anticancer, antiinflammatory, bone health and immunomodulation. The aim this study was to investigate of the acute effect of lactoferrin on paraoxonase activity, oxidant/antioxidant system and total protein, albumin and globulin. This study was carried out on 6-month Sprague Dawley rats in a total number of 20 subjects. Paraoxonase activity, total antioxidant capacity (TAC), total oxidant capacity (TOC), total protein, albumin and globulin levels were measured through the spectrophotometer. When the lactoferrin group was compared with the control group, it was found that TAC levels were statistically higher (P<0.05), TOC levels were statistically lower (P<0.01) and paraoxonase activity was statistically higher (P<0.05). There was no difference in total protein and globulin levels in the lactoferrin group compared to the control group. As a result, acute lactoferrin administration may play an important role in the regulation of antioxidant balance by increasing paraoxonase activity and decreasing the level of reactive oxygen species. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine (HCQ), an antimalarial drug widely used in treating rheumatoid disorders. Many side effects have been reported with HCQ administration indicating its hazardous effects on various organs. No previous studies reported the effect of long-term administration of oral HCQ on pancreatic tissue. Our study assessed pancreatic tissues functional and histopathological alterations following prolonged oral administration of HCQ. We also investigated the possible ameliorative effects of the lactoferrin (LF) coadministration with HCQ in adult male albino rats. Forty adult male Wister albino rats were divided into: negative control, LF positive control (2 g/kg), HCQ-treated (200 mg/kg), and HCQ+LF treated. Biochemical, histological, immunohistochemical, and morphometric analyses of the pancreatic tissues were conducted. Our findings revealed that prolonged oral administration of HCQ induced significant disruption of the pancreatic acinar architecture, enlarged congested islets of Langerhans, and elevated plasma insulin, amylase, and lipase levels. Interestingly, LF administration ameliorated the deleterious effects of prolonged HCQ administration on pancreatic tissue of adult male albino rats. In conclusion, prolonged oral administration of HCQ induced pancreatic tissue damage in rats, while LF attenuates HCQ-induced pancreatic injury. Our results emphasized the necessity of prescribing HCQ with caution, considering both dosage and treatment duration. [Display omitted] • Long-term oral HCQ administration disrupts pancreatic acinar architecture with enlarged congested islets of Langerhans. • Prolonged oral administration of HCQ induced elevation of plasma insulin, amylase, and lipase levels. • Administration of LF ameliorated the effects of prolonged oral administration of HCQ on the pancreatic tissues of adult male albino rats. • HCQ should be prescribed with caution, considering both dose and treatment duration. [ABSTRACT FROM AUTHOR]

Human lactoferrin (HLF), a pivotal iron-binding glycoprotein belonging to the transferrin family, is the primary immune protein in breast milk. Currently, recombinant HLF expression in microorganisms has attracted widespread attention. Through genome integration and copy number optimization, this study established a Komagataella phaffii cell factory that achieved an HLF titer of 137.6 mg/L. However, HLF accumulated extensively within the cells. Subsequently, several endogenous signal peptides were screened and hybridized with mating factor α, resulting in a 1.56-fold increase in extracellular HLF titers compared to the control. Additionally, protein kinase II overexpression facilitated vesicle trafficking, further increasing extracellular HLF to a titer of 304.6 mg/L in shake flasks and 1.7 g/L in a 3-L bioreactor. Notably, the intracellular/extracellular HLF concentration ratio decreased from 1.69:1 to 1.01:1. Further enhancements were made through ion optimization and an exponential methanol-feeding strategy, resulting in an extracellular HLF titer of 3.1 g/L. To the best of our knowledge, this is the first study to report considerably improved extracellular HLF production through optimization of the transport and secretion pathways and provide insights into the expression of other secretary human proteins in K. phaffii. [Display omitted] [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is one type of inflammatory bowel disease (IBD) and lactoferrin (LF) is a promising protein drug to treat UC. However, targeted LF delivery to optimize bioavailability, targeting and effectiveness remains a challenge. Here, we report an effective strategy to fabricate silk sericin nanospheres systems for the delivery of recombinant human lactoferrin (SS-NS-rhLF). The system is based on the use of optimized transgenic silkworms to generate genetically engineered silk fibers (rhLF-silks). The rhLF silks were used for fabricating SS-NS-rhLF by ethanol precipitation. The SS-NS-rhLF were stable with a spherical morphology with an average diameter of 123 nm. The negatively charged sericins in a pH ≥ 5.5 environment achieved specific targeting of the SS-NS-rhLF to positively charged colonic sites. The SS-NS-rhLF achieved efficient uptake by cells in the inflamed colon of mice when compared to free lactoferrin in solution (SOL-rhLF). Furthermore, oral administration of the SS-NS-rhLF with low dose of rhLF significantly relived symptoms of UC in mice and achieved comparable therapeutic effect to the high dose of SOL-rhLF by supporting the reformation of cell structure and length of colon tissue, reducing the release of inflammatory factors, inhibiting the activation of the NF-κB inflammatory pathway, and maintaining a stable intestinal microbial population in mice. These results showed that the SS-NS-rhLF is a promising system for colitis treatment. Targeting and effective delivery of multiple biological functional protein human lactoferrin (rhLF) is a promising strategy to treat ulcerative colitis in the clinic. Here, rhLF-transgenic silk cocoons were used to fabricate a rhLF-sericin nanosphere delivery system (SS-NS-rhLF). The fabricated SS-NS-rhLF showed identical spherical morphology, stable structure, sustainable rhLF release, efficient cell uptake and negative charge in an environment of pH above 5.5, thus realized the specific targeting to the positively charged colonic sites to treat UC mice through oral administration. The therapeutic effect of SS-NS-rhLF with a low rhLF dose in the UC mice was comparable to the high dose of free rhLF treatment in solution form, suggesting that the SS-NS-rhLF is a promising system for colitis treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

There is a close connection between epigenetic regulation, cancer metabolism, and immunology. The combination of epigenetic therapy and immunotherapy provides a promising avenue for cancer management. As an epigenetic regulator of histone acetylation, panobinostat can induce histone acetylation and inhibit tumor cell proliferation, as well as regulate aerobic glycolysis and reprogram intratumoral immune cells. JQ1 is a BRD4 inhibitor that can suppress PD-L1 expression. Herein, we proposed a chemo-free, epigenetic-based combination therapy of panobinostat/JQ1 for metastatic colorectal cancer. A novel targeted binary-drug liposome was developed based on lactoferrin-mediated binding with the LRP-1 receptor. It was found that the tumor-targeted delivery was further enhanced by in situ formation of albumin corona. The lactoferrin modification and endogenous albumin adsorption contribute a dual-targeting effect on the receptors of both LRP-1 and SPARC that were overexpressed in tumor cells and immune cells (e.g. , tumor-associated macrophages). The targeted liposomal therapy was effective to suppress the crosstalk between tumor metabolism and immune evasion via glycolysis inhibition and immune normalization. Consequently, lactic acid production was reduced and angiogenesis inhibited; TAM switched to an anti-tumor phenotype, and the anti-tumor function of the effector CD8+ T cells was reinforced. The strategy provides a potential method for remodeling the tumor immune microenvironment (TIME). The lactoferrin-modified and albumin-adsorbed liposome for targeting tumor microenvironment was designed for epigenetic-based combination therapy. This tumor-targeting liposome can activate anti-tumor immunity responses, inhibit aerobic glycolysis and angiogenesis, and restrict tumor growth and metastasis via epigenetic regulation. [Display omitted] [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the concentrations of antimicrobial components (immunoglobulin A (IgA), lactoferrin (LF), lingual antimicrobial peptide (LAP), and S100A7) in normal milk and their relation to host factors (Age, somatic cell count (SCC), days in milk, richness, and alpha diversity of the milk microbiota) in dairy cows using multivariate regression tree analyses, and to clarify how the milk microbiota is related to the obtained results. Thirty normal milk samples were collected from a commercial dairy farm in June 2020. The thresholds that predicted the concentration of each antimicrobial component in milk were obtained by regression tree analysis, and the beta-diversity of the milk microbiota composition between groups divided according to each threshold was compared by an analysis of similarities test. The IgA and LF concentrations were mainly predicted by the SCC (177,500 and 70,000 cells/ml, respectively), and the LAP and S100A7 concentrations were predicted by Age (29.667 and 40.3 months, respectively). No relationship was observed between the concentration of IgA, LAP, or S100A7 and the milk microbiota composition between the groups divided by the threshold for prediction, but the milk microbiota composition was significantly different between the groups divided by the threshold for predicting the LF concentration. Our results indicated that the LF concentration in normal milk may be associated with the milk microbiota composition. [ABSTRACT FROM AUTHOR]

Bovine lactoferrin (BLF) reportedly lowers blood pressure and induces vasorelaxation, but its effect on nitric oxide (NO) production has not been established. Accordingly, we aimed to determine whether BLF induces NO production in bovine aortic endothelial cells, and the effects of extracellular free magnesium (Mg) ion concentrations on this NO production. BLF induced NO production time-dependently. NO production was markedly inhibited by the NO synthase inhibitor, NG-nitro-L-arginine methyl ester, in an effect abolished by L-arginine, but not D-arginine. NO production was suppressed at low concentrations, and enhanced at high concentrations, of Mg ions in culture medium. These results suggest that BLF has an important role in hypotensive effects. Mg ions may affect BLF-induced NO production. [ABSTRACT FROM AUTHOR]

Genital bacterial infection is one of the most important causes of infertility, however, bacteria frequently exist in seminal fluid. Sperm express Toll-like receptors (TLRs) on their cell surfaces and bacterial recognition by TLRs induces sperm apoptosis. In this study, we examined the lactoferrin (LF) potentiality on sperm apoptosis induced by bacterial lipopolysaccharide (LPS). The TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay indicated that TUNEL-positive sperm cells were scarce in the group treated with LF and LPS (LF/LPS group) compared to the group treated with LPS only (LPS group). In addition, real-time RT-PCR detected lower mRNA expression levels of apoptosis-associated genes in the LF/LPS group compared to the LPS group. These results indicate that LF treatment of semen might decrease LPS-induced apoptosis of sperm. [ABSTRACT FROM AUTHOR]

Introduction: Exclusive breastfeeding, especially in the first six months, is essential for infants as it provides nutrition and protection against various diseases. Colostrum, which is found in the first breast milk produced, contains various protective factors, such as lactoferrin and lysozyme. Human milk can be stored at room temperature, refrigerated, or kept frozen. Several factors affect the stability of the bioactive content in human milk, such as temperature and storage time. The aim of this study was to measure the stability of lactoferrin and lysozyme levels in human milk during the first six hours (h) at different temperatures and compare it with that of frozen human milk. Methods: Human milk samples were obtained from 11 breastfeeding mothers using certain criteria. The human milk was stored at room temperature and 4°C for 1, 3, and 6 h and classified as never frozen, while frozen human milk was stored at -20°C for 1, 3, and 6 days. Measurement of the lactoferrin and lysozyme levels was performed using enzyme-linked immunosorbent assay. Results: The results showed that storage at room temperature significantly reduced lactoferrin and lysozyme levels. Lactoferrin levels in frozen human milk did not significantly decrease during the first six days. Meanwhile, the lysozyme levels in frozen human milk decreased significantly. Conclusion: The levels of lactoferrin and lysozyme in frozen human milk stored for the first six days were more stable than those stored at room temperature and 4°C in the first 6 h. [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf) is a natural iron-binding protein involved in coordinating specific and non-specific immune responses in humans. It exhibits broad spectrum antimicrobial properties against bacteria, viruses, and fungi. Owing to its high affinity for ferric (Fe+++) ions, Lf is responsible for controlling the oxidative stress in the body, and thus protects cells from oxygen injury. In addition, Lf is a natural immunomodulatory molecule that regulates the activity of the immune system. Lactoferrin present in saliva plays an important role in maintaining oral hygiene. It exhibits protective function on mucosal surfaces, which constitute a barrier between the host and the external environment. Thus, Lf may be considered as the first line of defense protein that is associated with oral mucosal immunity. Many studies indicate that lactoferrin supplementation is safe and beneficial for human health. The aim of this review is to discuss the effects of Lf on oral microflora, highlighting the potential significance of this protein in dental therapy and prevention of oral diseases. • Lactoferrin association with the oral mucosal immunity. • The preventing role of lactoferrin for the caries development. • Lactoferrin activity against pathogens responsible for periodontal diseases. • Lactoferrin role in the prevention of the oral candidiasis. [ABSTRACT FROM AUTHOR]

Currently, the COVID-19 pandemic, caused by the novel SARS-CoV-2 coronavirus, represents the greatest global health threat. Most people infected by the virus present mild to moderate respiratory symptoms and recover with supportive treatments. However, certain susceptible hosts develop an acute respiratory distress syndrome (ARDS), associated with an inflammatory "cytokine storm", leading to lung damage. Despite the current availability of different COVID-19 vaccines, the new emerging SARS-CoV-2 genetic variants represent a major concern worldwide, due to their increased transmissibility and rapid spread. Indeed, it seems that some mutations or combinations of mutations might confer selective advantages to the virus, such as the ability to evade the host immune responses elicited by COVID-19 vaccines. Several therapeutic approaches have been investigated but, to date, a unique and fully effective therapeutic protocol has not yet been achieved. In addition, steroid-based therapies, aimed to reduce inflammation in patients with severe COVID-19 disease, may increase the risk of opportunistic infections, increasing the hospitalization time and mortality rate of these patients. Hence, there is an unmet need to develop more effective therapeutic options. Here, we discuss the potential use of natural immunomodulators such as Thymosin α1 (Tα1), alltrans retinoic acid (ATRA), and lactoferrin (LF), as adjunctive or preventive treatment of severe COVID-19 disease. These agents are considered to be multifunctional molecules because of their ability to enhance antiviral host immunity and restore the immune balance, depending on the host immune status. Furthermore, they are able to exert a broad-spectrum antimicrobial activity by means of direct interactions with cellular or molecular targets of pathogens or indirectly by increasing the host immune response. Thus, due to the aforementioned properties, these agents might have a great potential in a clinical setting, not only to counteract SARS-CoV-2 infection, but also to prevent opportunistic infections in critically ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • Digestion of β-casein-lactoferrin coacervates was examined for the first time. • Formation of complex coacervates increased gastric stability of β-casein and lactoferrin. • Complex coacervates showed altered in vitro digestion, impacting peptide profiles. • The C-terminal of β-casein was protected from digestion in complex coacervates. Lactoferrin is of interest for infant nutrition due to its roles in supporting gastrointestinal development. When supplemented orally, digestive exposure may reduce the availability and biofunctionality of the protein and its derived peptides. The aim of this study was to evaluate the proteolysis of bovine lactoferrin and β-casein coacervates following infant in vitro digestion. Coacervation of β-casein with lactoferrin showed a protective function against peptic proteolysis, increasing the levels of intact β-casein and lactoferrin during gastric digestion, while the uncomplexed β-casein was readily proteolyzed. The coacervate was shown to protect the C-terminal of β-casein against gastric proteolysis. This resulted in altered peptide profiles in the gastric and intestinal phases, requiring additional research to ascertain potential implications for biological activity. This study demonstrates the impact of protein–protein interactions on proteolysis during digestion, which may delay proteolysis and possibly protect the bioactive properties of the proteins. [ABSTRACT FROM AUTHOR]

Co-delivery of antigens and adjuvants in a nanoparticle format could be beneficial for subunit vaccine development. Herein, we develop a nanovaccine comprising la ctoferrin- M n- P EG-di A BZI-2-antigen, termed LaMP-A-antigen. Featuring a metalloprotein core, LaMP securely localizes manganese (Mn) in confined spaces formed by lactoferrin-PEG conjugates. LaMP efficiently coordinates imidazole-containing adjuvants (diABZI-2), yielding LaMP-A, which is subsequently functionalized by numerous his-tagged viral-derived antigenic proteins or peptides by simple admixture. Compared to regular metal chelation, LaMP-A-antigen is more physiologically stable and can be lyophilized and stored at room temperature without change in physical and immunological properties for months. Following screening of ten common metal ions, manganese and cobalt are found to enhance the adjuvant effect of diABZI-2 by activation of stimulator of interferon genes (STING). In particular, Mn2+ achieves a 39-fold adjuvant dose sparing effect. When the SARS-CoV-2 receptor-binding domain (RBD) is used as a model antigen, immunization with LaMP-A-RBD elicits strong mucosal, humoral and cellular immunity. Following a single intranasal administration of LaMP-A-RBD in hamsters, antigen-specific T cells as well as natural killer (NK) cells are induced, along with RBD-specific IgG and secretory IgA (sIgA), leading to rapid neutralization in a reporter pseudovirus challenge. Thus, the LaMP-A system represents a novel vaccine adjuvant system that displays antigens, and exploits metalloimmune responses via the cGAS-STING pathway to improve vaccine immunogenicity. [Display omitted] • A physiologically stable and lyophilisable metalloprotein scaffold used for co delivery of antigens and adjuvants is designed. • Versatile viral antigens can be readily conjugated to the metal-based vaccine nanoplatform for strong mucosal, cellular, and humoral immune responses. • Mn2+, in combination with the newly synthesized adjuvant, termed diABZI-2, can synergistically activate cGAS-STING to fight against viral infections. [ABSTRACT FROM AUTHOR]