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  1. Khanum R, Chung PY, Clarke SC, Chin BY
    Can J Microbiol, 2023 Feb 01;69(2):117-122.
    PMID: 36265186 DOI: 10.1139/cjm-2022-0135
    Lactoferrin is an innate glycoprotein with broad antibacterial and antibiofilm properties. The autonomous antibiofilm activity of lactoferrin against Gram-positive bacteria is postulated to involve the cell wall and biofilm components. Thus, the prevention of biomass formation and eradication of preformed biofilms by lactoferrin was investigated using a methicillin-resistant Staphylococcus epidermidis (MRSE) strain. Additionally, the ability of lactoferrin to modulate the expression of the biofilm-associated protein gene (bap) was studied. The bap gene regulates the production of biofilm-associated proteins responsible for bacterial adhesion and aggregation. In the in vitro biofilm assays, lactoferrin prevented biofilm formation and eradicated established biofilms for up to 24 and 72 h, respectively. Extensive eradication of MRSE biofilm biomass was accompanied by the significant upregulation of bap gene expression. These data suggest the interaction of lactoferrin with the biofilm components and cell wall of MRSE, including the biofilm-associated protein.
    Matched MeSH terms: Lactoferrin/genetics; Lactoferrin/pharmacology
  2. Ali AS, Hasan SS, Kow CS, Merchant HA
    Clin Nutr ESPEN, 2021 10;45:26-32.
    PMID: 34620326 DOI: 10.1016/j.clnesp.2021.08.019
    BACKGROUND: Lactoferrin (Lf) is one of the key immunomodulatory substances found naturally in various body fluids, such as saliva, tears, and breast milk, and forms a vital part of the innate defense against invading pathogens. Various studies have demonstrated antibacterial, antifungal, and antiviral properties of Lf and its protective role against respiratory tract infections (RTIs). The present meta-analysis aims to elucidate the association of Lf administration in reducing the risk of RTIs by systematically reviewing the data from randomized controlled trials (RCTs).

    METHODS: We systematically searched PubMed, Cochrane Library, Medline & CINAHL, Turning Research into Practice (TRIP), ProQuest Theses & Dissertations Databases, and China National Knowledge Infrastructure (CNKI) from inception till March 15, 2021. The primary outcome measure was a reduction in respiratory illness; decrease in frequency, symptoms, and duration. Random-effects model was used to estimate the odds ratio (OR) and 95% confidence interval (CI). We used Cochrane's RoB-2 to appraise the risk of bias of included RCTs.

    RESULTS: A total of nine RCTs were eligible for this review, of which six were included in the meta-analysis. Overall, two studies demonstrated a high risk of bias. The meta-analysis revealed a significantly reduced odds of developing respiratory infections with the use of Lf relative to the control (pooled odds ratio = 0.57; 95% confidence interval 0.44 to 0.74, n = 1,194), with sufficient evidence against the hypothesis of 'no significant difference' at the current sample size.

    CONCLUSIONS: The administration of Lf shows promising efficacy in reducing the risk of RTIs. Current evidence also favours Lf fortification of infant formula. Lf may also have a beneficial role in managing symptoms and recovery of patients suffering from RTIs and may have potential for use as an adjunct in COVID-19, however this warrants further evidence from a large well-designed RCT.

    Matched MeSH terms: Lactoferrin
  3. Rahman R, Fonseka AD, Sua SC, Ahmad M, Rajendran R, Ambu S, et al.
    J Cell Mol Med, 2021 08;25(15):7181-7189.
    PMID: 34236134 DOI: 10.1111/jcmm.16748
    Breast cancer has a diverse aetiology characterized by the heterogeneous expression of hormone receptors and signalling molecules, resulting in varied sensitivity to chemotherapy. The adverse side effects of chemotherapy coupled with the development of drug resistance have prompted the exploration of natural products to combat cancer. Lactoferricin B (LfcinB) is a natural peptide derived from bovine lactoferrin that exhibits anticancer properties. LfcinB was evaluated in vitro for its inhibitory effects on cell lines representing different categories of breast cancer and in vivo for its suppressive effects on tumour xenografts in NOD-SCID mice. The different breast cancer cell lines exhibited varied levels of sensitivity to apoptosis induced by LfcinB in the order of SKBR3>MDA-MB-231>MDA-MB-468>MCF7, while the normal breast epithelial cells MCF-10A were not sensitive to LfcinB. The peptide also inhibited the invasion of the MDA-MB-231 and MDA-MB-468 cell lines. In the mouse xenograft model, intratumoural injections of LfcinB significantly reduced tumour growth rate and tumour size, as depicted by live imaging of the mice using in vivo imaging systems (IVIS). Harvested tumour volume and weight were significantly reduced by LfcinB treatment. LfcinB, therefore, is a promising and safe candidate that can be considered for the treatment of breast cancer.
    Matched MeSH terms: Lactoferrin/pharmacology; Lactoferrin/therapeutic use*
  4. Taguchi K, Chuang VTG, Hashimoto M, Nakayama M, Sakuragi M, Enoki Y, et al.
    Chem Pharm Bull (Tokyo), 2020;68(8):766-772.
    PMID: 32741918 DOI: 10.1248/cpb.c20-00222
    Lactoferrin (Lf) nanoparticles have been developed as a carrier of drugs and gene. Two main methods, desolvation technique and emulsification method, for preparation of protein nanoparticles have been reported so far, but most of the previous reports of Lf nanoparticles preparation are limited to emulsification method. In this study, we investigated the optimal conditions by desolvation technique for the preparation of glutaraldehyde-crosslinked bovine Lf (bLf) nanoparticles within the size range of 100-200 nm, and evaluated their properties as a carrier for oral and intravenous drug delivery. The experimental results of dynamic light scattering and Transmission Electron Microscope suggested that glutaraldehyde-crosslinked bLf nanoparticles with 150 nm in size could be produced by addition of 2-propanol as the desolvating solvent into the bLf solution adjusted to pH 6, followed by crosslinking with glutaraldehyde. These cross-linked bLf nanoparticles were found to be compatible to blood components and resistant against rapid degradation by pepsin. Thus, cross-linked bLf nanoparticles prepared by desolvation technique can be applied as a drug carrier for intravenous administration and oral delivery.
    Matched MeSH terms: Lactoferrin/blood; Lactoferrin/chemistry*
  5. Juzaily Husain
    MyJurnal
    The development of treatment strategies for periodontitis that maximise the
    effectiveness of antibiotics is highly desirable. Azithromycin is proving to be an effective antibiotic
    for treatment of refractory periodontitis which works by binding to the outer membrane of Gramnegative bacteria and subsequently inhibits protein synthesis. Lactoferrin is a membrane-active
    host antimicrobial protein and so the objective of this study was to determine whether the effect
    of azithromycin (AZM) against example periodontopathogens (Porphyromonas gingivalis and
    Tannerella forsythia) could be potentiated by lactoferrin. (Copied from article).
    Matched MeSH terms: Lactoferrin
  6. Leng KM, Vijayarathna S, Jothy SL, Sasidharan S, Kanwar JR
    Future Sci OA, 2018 Feb;4(2):FSO257.
    PMID: 29379633 DOI: 10.4155/fsoa-2017-0085
    Aim: To study the in vitro and in vivo anticandidal activity of nanocapsulated bovine lactoferrin.

    Materials & methods: In vitro and in vivo antimicrobial activities were conducted to study the anticandidal activities of nanocapsules (NCs).

    Results: The NCs showed good anticandidal activities. The disruption of cell wall and cell membrane was noted via microscopy studies. The NCs changed the normal growth profile of Candida albicans. NCs reduced the colony forming unit in kidney and blood samples. Histopathological examination showed better cell structure and coordination compared with untreated mice kidney. NCs also enhanced the natural killing properties of C. albicans by epithelial cells.

    Conclusion: NCs have effective anticandidal properties and have the potential as a therapeutic agent against candidiasis.

    Matched MeSH terms: Lactoferrin
  7. Lalani S, Gew LT, Poh CL
    Peptides, 2021 Feb;136:170443.
    PMID: 33171280 DOI: 10.1016/j.peptides.2020.170443
    The emergence of new and resistant viruses is a serious global burden. Conventional antiviral therapy with small molecules has led to the development of resistant mutants. In the case of hand, foot and mouth disease (HFMD), the absence of a US-FDA approved vaccine calls for urgent need to develop an antiviral that could serve as a safe, potent and robust therapy against the neurovirulent Enterovirus A71 (EV-A71). Natural peptides such as lactoferrin, melittin and synthetic peptides such as SP40, RGDS and LVLQTM have been studied against EV-A71 and have shown promising results as potent antivirals in pre-clinical studies. Peptides are considered safe, efficacious and pose fewer chances of resistance. Poor pharmacokinetic features of peptides can be overcome by the use of chemical modifications to improve in vivo delivery particularly by oral route. The use of nanotechnology can remarkably assist in the oral delivery of peptides and enhance stability in vivo. This can greatly increase patient compliance and make it more attractive as antiviral therapy.
    Matched MeSH terms: Lactoferrin
  8. Mohd Ali, B., Nguan, D.K.C., Bashirah, I., Chan, K.M.
    MyJurnal
    Changes in tear protein concentrations may reflect ocular surface health. This study analyzes changes in tear protein concentrations of young Malays with dry eye (DE) and determines its association with the clinical findings. Methods: Subjects were screened using McMonnies questionnaire (MDEQ) and flourescein tear break up time (TBUT). Total tear protein concentration (TTPC) was determined using Bradford's technique and specific tear protein (sIgA, lysozyme, lactoferrin and human serum albumin (HSA)) concentrations were determined using SDS-PAGE. Parametric and nonparametric tests were used to compare means between groups. Spearman correlation was used to determine the association between variables measured. Results: A total of 42 subjects (21 DE and 21 NDE) were included. Mean MDEQ score for DE was 16.00±1.48 and NDE was 8.47±3.47. Mean TBUT for DE was 3.47±0.47s and NDE was 4.98±0.43s. Mean TTPC for DE and NDE was 9.84±2.40mg/ml and 8.96±1.84mg/ml respectively. Mean sIgA, lysozyme, lactoferrin and HSA for DE was 0.54±0.10mg/ml, 1.68±0.17mg/ml, 1.47±0.25mg/ml, 0.06±0.03mg/ml and for NDE was 0.57±0.09mg/ml, 2.04±0.19mg/ml, 1.75±0.23mg/ml, 0.06±0.03mg/ml accordingly. Significant differences were noted in MDEQ score (p=0.01), TBUT (p=0.01), lactoferrin (p=0.01) and lysozyme (p=0.01) but not in TTPC (p=0.19), HSA (p=0.74) and sIgA (p=0.24) between groups. Significant correlations were noted between TBUT with lactoferrin (r=0.02, p=0.02) and lysozyme (r=0.63, p=0.01) and between MDEQ score with lactoferrin (r=-0.34, p=0.02) and lysozyme (r=-0.64, p=0.01). Conclusions: There are changes in specific tear protein in dry eye patients, which correlate well with clinical results. Tear protein analysis may play an important role in the diagnosis of the dry eye.
    Matched MeSH terms: Lactoferrin
  9. Agarwal A, Durairajanayagam D, Halabi J, Peng J, Vazquez-Levin M
    Reprod Biomed Online, 2014 Jul;29(1):32-58.
    PMID: 24813754 DOI: 10.1016/j.rbmo.2014.02.013
    Oxidative stress has been established as one of the main causes of male infertility and has been implicated in many diseases associated with infertile men. It results from high concentrations of free radicals and suppressed antioxidant potential, which may alter protein expression in seminal plasma and/or spermatozoa. In recent years, proteomic analyses have been performed to characterize the protein profiles of seminal ejaculate from men with different clinical conditions, such as high oxidative stress. The aim of the present review is to summarize current findings on proteomic studies performed in men with high oxidative stress compared with those with physiological concentrations of free radicals, to better understand the aetiology of oxidative stress-induced male infertility. Each of these studies has suggested candidate biomarkers of oxidative stress, among them are DJ-1, PIP, lactotransferrin and peroxiredoxin. Changes in protein concentrations in seminal plasma samples with oxidative stress conditions were related to stress responses and to regulatory pathways, while alterations in sperm proteins were mostly associated to metabolic responses (carbohydrate metabolism) and stress responses. Future studies should include assessment of post-translational modifications in the spermatozoa as well as in seminal plasma proteomes of men diagnosed with idiopathic infertility. Oxidative stress, which occurs due to a state of imbalance between free radicals and antioxidants, has been implicated in most cases of male infertility. Cells that are in a state of oxidative stress are more likely to have altered protein expression. The aim of this review is to better understand the causes of oxidative stress-induced male infertility. To achieve this, we assessed proteomic studies performed on the seminal plasma and spermatozoa of men with high levels of oxidative stress due to various clinical conditions and compared them with men who had physiological concentrations of free radicals. A variety of sperm and seminal plasma proteins were found to be expressed either in abundance (over-expressed) or in a lesser amount (underexpressed), while other proteins were found to be unique either to men with oxidative stress or to men with a balanced ratio of antioxidants/free radicals. Each study included in this review suggested several proteins that could possibly act as biomarkers of oxidative stress-induced male infertility, such as protein DJ-1, PIP, lactotransferrin and peroxiredoxin. Pathway analysis performed in these studies revealed that the changes in seminal plasma proteins in men with oxidative stress could be attributed to stress responses and regulatory pathways, while changes in sperm proteins were linked to stress responses and metabolic responses. Subsequent studies could look into post-translational modifications in the protein profile of men with idiopathic infertility. We hope that the information in this review will contribute to a better understanding of the main causes of idiopathic male infertility.
    Matched MeSH terms: Lactoferrin/metabolism
  10. Hou Z, Imam MU, Ismail M, Azmi NH, Ismail N, Ideris A, et al.
    Biosci Biotechnol Biochem, 2015;79(10):1570-8.
    PMID: 26057702 DOI: 10.1080/09168451.2015.1050989
    There are reports of improved redox outcomes due to consumption of Edible Bird's Nest (EBN). Many of the functional effects of EBN can be linked to its high amounts of antioxidants. Interestingly, dietary components with high antioxidants have shown promise in the prevention of aging and its related diseases like Alzheimer's disease. In this study, the antioxidative potentials of EBN and its constituents, lactoferrin (LF) and ovotransferrin (OVF), were determined and protective effects against hydrogen peroxide (H2O2)- induced toxicity on SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acridine orange and propidium iodide (AO/PI) staining with microscopy were examined. Results showed that EBN and its constituents attenuated H2O2-induced cytotoxicity, and decreased radical oxygen species (ROS) through increased scavenging activity. Furthermore, LF, OVF, and EBN produced transcriptional changes in antioxidant related genes that tended towards neuroprotection as compared to H2O2-treated group. Overall, the results suggest that LF and OVF may produce synergistic or all-or-none antioxidative effects in EBN.
    Matched MeSH terms: Lactoferrin/isolation & purification; Lactoferrin/pharmacology*
  11. Leng KM, Vijayarathna S, Jothy SL, Sasidharan S, Kanwar JR
    Biomed Pharmacother, 2018 Jan;97:26-37.
    PMID: 29080455 DOI: 10.1016/j.biopha.2017.10.121
    Lactoferrin has been known to have antimicrobial properties. This research was conducted to investigate the toxicity of Alginate/EUDRAGIT® S 100-enclosed chitosan-calcium phosphate-loaded Fe-bLf nanocapsules (NCs) by in vitro and in vivo assays. Brine shrimp lethality assay showed that the LC50 value of NCs was more than 1mg/mL which indicated that NCs was not toxic to Brine shrimp. However, the LC50 values for the positive control potassium dichromate at 24h is 64.15μg/mL, which was demostrated the toxic effect against the brine shrimp. MTT cytotoxicity assay also revealed that NCs was not toxic against non-cancerous Vero cell line with IC50 values of 536μg/mL. Genotoxicity studies by comet assay on Vero cells revealed that NCs exerted no significant genotoxic at 100μg/mL without tail or shorter comet tail. Allium cepa root assay carried out at 125, 250, 500 and 1000μg/mL for 24h revealed that the NCs was destitute of significant genotoxic effect under experimental conditions. The results show that there is no significant difference (p>0.05) in mitotic index between the deionized water and NCs treated Allium cepa root tip cells. In conclusion, no toxicity was observed in NCs in this study. Therefore, nontoxic NCs has the good potential to develop as a therapeutic agent.
    Matched MeSH terms: Lactoferrin/administration & dosage; Lactoferrin/toxicity*
  12. Halder A, Jethwa M, Mukherjee P, Ghosh S, Das S, Helal Uddin ABM, et al.
    Artif Cells Nanomed Biotechnol, 2020 Nov 17;48(1):1362-1371.
    PMID: 33284038 DOI: 10.1080/21691401.2020.1850465
    Cancer management presents multifarious problems. Triple negative breast cancer (TNBC) is associated with inaccurate prognosis and limited chemotherapeutic options. Betulinic acid (BA) prevents angiogenesis and causes apoptosis of TNBC cells. NIH recommends BA for rapid access in cancer chemotherapy because of its cell-specific toxicity. BA however faces major challenges in therapeutic practices due to its limited solubility and cellular entree. We report lactoferrin (Lf) attached BA nanoparticles (Lf-BAnp) for rapid delivery in triple negative breast (MDA-MB-231) and laryngeal (HEp-2) cancer cell types. Lf association was confirmed by SDS-PAGE and FT-IR analysis. Average hydrodynamic size of Lf-BAnp was 147.7 ± 6.20 nm with ζ potential of -28.51 ± 3.52 mV. BA entrapment efficiency was 75.38 ± 2.70% and the release mechanism followed non-fickian pattern. Impact of Lf-BAnp on cell cycle and cytotoxicity of triple negative breast cancer and its metastatic site laryngeal cancer cell lines were analyzed. Lf-BAnp demonstrated strong anti-proliferative and cytotoxic effects, along with increased sub-G1 population and reduced number of cells in G1 and G2/M phases of the cell cycle, confirming reduced cell proliferation and significant cell death. Speedy intracellular entry of Lf-BAnp occurred within 30 min. Lf-BAnp design was explored for the first time as safer chemotherapeutic arsenals against complex TNBC conditions.
    Matched MeSH terms: Lactoferrin/chemistry*
  13. Suleman Ismail Abdalla S, Katas H, Chan JY, Ganasan P, Azmi F, Fauzi MB
    Mol Pharm, 2021 05 03;18(5):1956-1969.
    PMID: 33822631 DOI: 10.1021/acs.molpharmaceut.0c01033
    Gelatin hydrogels are attractive for wound applications owing to their well-defined structural, physical, and chemical properties as well as good cell adhesion and biocompatibility. This study aimed to develop gelatin hydrogels incorporated with bio-nanosilver functionalized with lactoferrin (Ag-LTF) as a dual-antimicrobial action dressing, to be used in treating infected wounds. The hydrogels were cross-linked using genipin prior to loading with Ag-LTF and characterized for their physical and swelling properties, rheology, polymer and actives interactions, and in vitro release of the actives. The hydrogel's anti-biofilm and antibacterial performances against S. aureus and P. aeruginosa as well as their cytotoxicity effects were assessed in vitro, including primary wound healing gene expression of human dermal fibroblasts (HDFs). The formulated hydrogels showed adequate release of AgNPs and LTF, with promising antimicrobial effects against both bacterial strains. The Ag-LTF-loaded hydrogel did not significantly interfere with the normal cellular functions as no alteration was detected for cell viability, migration rate, and expression of the target genes, suggesting the nontoxicity of Ag-LTF as well as the hydrogels. In conclusion, Ag-LTF-loaded genipin-cross-linked gelatin hydrogel was successfully synthesized as a new approach for fighting biofilms in infected wounds, which may be applied to accelerate healing of chronic wounds.
    Matched MeSH terms: Lactoferrin/chemistry
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