Lactoferrin Levels Research Articles

Changes in tear cytokine and lactoferrin levels in postmenopausal women with primary acquired nasolacrimal duct obstruction complicated with obstructed meibomian gland dysfunction

BackgroundEpiphora and secondary ocular surface damage are increasingly impairing the quality of life of people, particularly elderly women. We aimed to investigate the changes in tear cytokine and lactoferrin levels in postmenopausal women with primary acquired nasolacrimal duct obstruction (PANDO) complicated with obstructed meibomian gland dysfunction (OMGD) and preliminary explore the pathological mechanisms of OMGD in patients with PANDO.MethodsThe prospective study involved 43 and 41 postmenopausal women with and without PANDO, respectively. Based on the presence or absence of OMGD, the participants were subdivided. Tear fluid was collected from affected eyes of all participants using Schirmer I test and tested for cytokine concentrations (interleukin (IL)-6, IL-8, IL-1β, interferon-gamma, tumour necrotic factor (TNF)-α, IL-10, epidermal growth factor (EGF)) using the Multiplex Luminex Assay. Tear lactoferrin levels was determined using ELISA.ResultsIn the PANDO with OMGD group, the IL-8, IL-1α, IL-1β, and macrophage inflammatory protein-1α levels were significantly higher than those in the other groups. The IL-6 and TNF-α levels were significantly higher than those in the controls. The lactoferrin level in the PANDO with OMGD group was lower than that in the Non-PANDO with OMGD group. The IL-10 and EGF levels were not significantly different among the groups.ConclusionThe level of pro-inflammatory factors in the tears of patients with PANDO complicated with OMGD was significantly increased, which is likely to cause further damage to ocular surface. Anti-inflammatory therapy may help protect ocular surface in postmenopausal women with PANDO.

Vitamin D supplementation modifies clinical and biological markers of keratoconus progression

Aims/Purpose: evaluation of vitamin D (Vit D) supplementation on clinical progression and systemic biomarkers in adolescent patients affected by keratoconus (KC) and Vit D insufficiency.Methods: forty adolescent patients (age range: 12–19) meeting the criteria of KC diagnosis and Vit D insufficiency ( < 30 ng/mL) were enrolled and followed for 12 months. Vit D supplementation was prescribed for the first 6 months and patients were then followed up for additional 6 months. Clinical parameters, including best spectacle‐corrected visual acuity, maximal keratometry, and corneal thickness were measured at month 0, 2, 4, 6, 9, 12 after enrollment to monitor the KC progression. Moreover, at month 0 and 6 after enrollment we evaluated serum biomarkers, including Vit D levels and metabolism, collagen degradation, and inflammation by ELISA and RT‐PCR.Results: after 6 months of Vit D supplementation, serum Vit D levels were significantly increased and remained clinically stable up to month 12. Two‐thirds of patients responded to treatment and showed KC stabilization 12 months after enrollment. Interestingly, Vit D receptor was upregulated only in stable patients (p < 0.01) at month 6. Serum markers indicated that type I collagen degradation product, procollagen type I carboxyl‐terminal propeptide, and the ratio between matrix metalloproteinase 9 and tissue inhibitor of matrix metalloproteinase 1 were statistically decreased (p < 0.05) only in stable patients. Vit D supplementation was associated with increased expression of CD 14 (p < 0.0001) and decreased levels of lactoferrin (p < 0.0001).Conclusions: these data demonstrated that Vit D treatment stabilized KC progression in the majority of patients. These stable patients showed reduced systemic inflammation and collagen catabolism, thus suggesting that KC could be considered a systemic disease.

Effect Cryptosporidium parvum on Lactoferrin level in children with diarrhea

Cryptosporidium spp. are a group of coccidian parasites of significant pathogenicity to both animals and humans. Cryptosporidiosis is understood to be the underlying factor behind the development of severe and protracted watery diarrhea in individuals diagnosed with acquired immunodeficiency syndrome. This study aimed to diagnosis of infection with the parasite Cryptosporidium parvum in children by microscopic examination of stool samples using the Modified Ziehl-Nelsoon stain and ELISA. As well as detection level of Lactoferrin in samples of patients infected with Cryptosporidium parvum . A total 300 samples children aged 5 months - 5 years, of both sexes, who visited some government hospitals (Tikrit Teaching Hospital, Salah al-Din General Hospital, Baiji General Hospital, Sharqat General Hospital) and some private medical clinics in some areas of Salah al-Din Governorate who suffered from diarrhea and some intestinal symptoms during the period from July 1, 2022 to September 1, 2023. Based on the analysis of 300 stool samples, the present investigation employing MZN revealed an infection rate of 70 (23.33%) positive samples and 230 (76.67%) negative samples. The ELISA technique used in the current study recorded 130 positive samples and a total infection rate of 72.22% with a mean concentration of 2.54±1.13 pg/mL), while the number of negative samples was 50 (27.78%) with a mean concentration of (27.78%) pg/mL out of 90 samples. This study showed increase incidence of infection with cryptosporidium in male than female that were 82(63.08%) and 48(36.92%) respectively, at p-value<0.05. The study observed a significant increase in the average concentration of fecal LF in infected infants (506.125 ± 99.143 pg/mL) compared to the control group (104.183 ± 21.368pg/ml). This study concluded that Modified Ziehl Neelsen stain is the best staining method used in diagnosing infection with the parasite. . Furthermore this study concluded increase level inflammatory immune parameters as lactoferrine in blood serum and stool samples of children infected with the C. parvum parasite

The Association of Serum Lactoferrin Level with Psychological Symptoms, Cognition, and Executive Function in Schizophrenia Patients

Objective: Lactoferrin, a glycoprotein, has known neuroprotective effects, yet its role in the pathophysiology of neuropsychiatric disorders, particularly schizophrenia, remains unclear. This study aims to assess changes in lactoferrin levels during different phases of schizophrenia and explore its relationship with cognitive symptoms and performance. Method: This before/after interventional study involved 30 patients diagnosed with schizophrenia. Participants were evaluated at two time points: upon hospital admission and after the resolution of acute symptoms. The Positive and Negative Syndrome Scale (PANSS) was utilized to measure symptom severity, while the Brief Assessment of Cognition in Schizophrenia (BACS) assessed the neurocognitive function. Serum lactoferrin levels were quantified using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Results: Serum lactoferrin levels significantly decreased from 130.63 ± 52.49 ng/mL at admission to 85.42 ± 29.03 ng/mL at discharge (P < 0.001). No significant correlation was found between lactoferrin levels and PANSS scores (r = 0.011, P = 0.975). However, an inverse correlation was observed between changes in lactoferrin levels and the executive function subscale of the BACS (r = -0.360, P = 0.050). Cognitive assessments indicated significant improvements in verbal memory (P = 0.033), working memory (P = 0.002), and executive function (P = 0.039) post-treatment. Conclusion: The study demonstrates a significant reduction in serum lactoferrin levels during the acute phase of schizophrenia, suggesting its potential role in modulating cognitive functions, particularly the executive function, rather than influencing positive or negative symptoms.

Serum thioredoxin and lactoferrin in rheumatoid arthritis and their association with rheumatoid factor

Background: Thioredoxin (Trx) and lactoferrin (Lf) are multifunctional proteins part of the body anti-oxidant defence and counteract the oxidative tissue damage. The purpose of our study is to investigate Trx and Lf levels in serum of rheumatoid arthritis (RA) patients and establish the association of these proteins with the rheumatoid factor (RF) and other disease markers. Methods: The study included 114 patients with RA and 42 healthy subjects. Serum concentrations of Trx, Lf, RF, anti-cyclic citrullinated peptide (anti-CCP) antibodies, CRP, and IL-6 were determined using commercially available ELISA kits. Results: Serum thioredoxin levels in RA were significantly higher compared to the control group, 36.4 (29.6-40.2), ng/mL versus 19.0 (16.3-26.8), ng/mL, p < 0.0001. Serum lactoferrin levels were elevated in RA compared to the control group but the difference was not statistically significant, 579.6 (312.8-947.5), ng/mL versus 519.0 (262.5-928.0), ng/mL. We found significant negative correlations of Trx and Lf with rheumatoid factor in RA (r= -0.254, p=0.05 and r= -0.238, p=0.014, respectively). The correlations of thioredoxin and lactoferrin with other disease markers such as anti-CCP antibodies, DAS28, ESR, CRP, and IL-6 were not statistically significant. A strong positive correlation between Trx and Lf was observed in the study group of RA patients (r=0.519, p<0.0001), but not in the control group. Conclusions: Thioredoxin and lactoferrin were associated with rheumatoid factor, but not with anti-CCP antibodies and systemic disease activity, therefore the two proteins may serve as new biomarkers for assessment of pathological changes and monitoring of disease severity and progression in RA.

Denture microbiome shift and changes of salivary inflammatory markers following insertion of 3D printed removable partial PMMA denture: a pilot study

BackgroundThe aim of this study was to investigate the microbiome shift of denture biofilm formation, the incidence of Candida and changes of salivary inflammatory markers following insertion of 3-dimensional printed PMMA denture.MethodsThis was a pilot study of 6 patients provided with 3D printed (test group) or conventionally heat-cured (control group) removable partial acrylic dentures followed up for 6 weeks. 3 denture swabs were collected at week 1, 3 and 6; and saliva samples were collected at baseline, week 1, 3 and 6 following denture insertion. Microbial DNA was isolated, and the 16S rRNA gene was amplified and sequenced to assess the denture microbiota. The presence of Candida was determined using PCR assay. The levels of salivary biomarkers lactoferrin (LTF) and histatin (HTN) were determined using ELISA.ResultsDenture microbiome of both groups exhibited similar microbial compositions at weeks 1, 3 and 6. However, the percentage of Streptococcus in the test group was significantly lower at week 1 (p < 0.05). Greater bacterial diversity was detected in the test group (p < 0.05; pairwise Wilcoxon) after 6 weeks. The presence of Candida was only detected in one sample of the 3D printed denture (test group) after 6 weeks. The level of LTF biomarkers increased in both groups after 6 weeks, however, the level of HTN increased only in the control group.ConclusionsDenture microbiome of both groups demonstrated similar microbial compositions. After 6 weeks, 3D printed denture demonstrated higher diversity with delayed microbiome shift compared to conventional heat cure dentures. 3D printed denture may be a viable alternative to conventional denture and it has a potential to delay microbial dysbiosis.Clinical RelevanceAmong wearers, 3D printed denture can potentially reduce the risk of denture stomatitis. A greater diversity may delay or slow the transition of denture microbiome to dysbiosis.

Astrocytic lactoferrin deficiency augments MPTP-induced dopaminergic neuron loss by disturbing glutamate/calcium and ER-mitochondria signaling

Increased levels of lactoferrin (Lf) are present in the aged brain and in the lesions of various neurodegenerative diseases, including Parkinson's disease (PD), and may contribute to the cascade of events involved in neurodevelopment and neuroprotection. However, whether Lf originates from astrocytes and functions within either the normal or pathological brain are unknown. Here, we employed mice with specific knockout of the astrocyte lactoferrin gene (named Lf-cKO) to explore its specific roles in the pathological process of PD. We observed a decrease in tyrosine hydroxylase-positive cells, mitochondrial dysfunction of residual dopaminergic neurons, and motor deficits in Lf-cKO mice, which were significantly aggravated after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. To further explore how astrocytic lactoferrin deficiency exacerbated PD-like manifestation in MPTP-treated mice, the critical molecules involved in endoplasmic reticulum (ER)-mitochondria contacts and signaling pathways were investigated. In vitro and in vivo models, we found an aberrant level of effects implicated in glutamate and calcium homeostasis, mitochondrial morphology and functions, mitochondrial dynamics, and mitochondria-associated ER membranes, accompanied by signs of oxidative stress and ER stress, which increase the fragility of dopaminergic neurons. These findings confirm the existence of astrocytic Lf and its influence on the fate of dopaminergic neurons by regulating glutamate/calcium metabolism and ER-mitochondria signaling. Our findings may be a promising target for the treatment of PD.

Detection of Lactoferrin and Iron in Seminal Plasma and Their Possible Relation to Semen Parameters and Infertility in Varicocele: A Cross-sectional Study.

Male infertility emerges as an important cause during the evaluation of infertile couples. Varicocele is a well-known cause of male infertility. The role of seminal lactoferrin, an iron-binding glycoprotein, in male fertility is unclear and needs further investigation. Recently, it has been linked to some sperm abnormalities and subfertility. This study aims to detect seminal lactoferrin levels in infertile men with varicocele and their relation to semen parameters and fertility status. We investigated a possible link between seminal lactoferrin and iron. A cross-sectional study was conducted through the outpatient clinic. Seventy-five individuals were included in 3 groups (33 infertile men with varicocele, 25 infertile men without varicocele and 17 fertile participants without varicocele). Conventional semen analysis was conducted, and seminal plasma was obtained in all groups to detect lactoferrin and iron levels. Statistical analysis was performed by SPSS version 24. In infertile men with varicocele, seminal lactoferrin (155.92 ± 8.4 ng/ml, P = 0.296) and iron levels (260.71 ± 38.3 μg/dl, P = 0.409) were not significantly different from other groups. There was a positive correlation between seminal lactoferrin, iron levels and sperm concentrations and counts. Seminal iron and lactoferrin were significant independent predictors of sperm concentration. A negative correlation was reported between seminal lactoferrin levels and age. Lactoferrin in seminal plasma was not correlated with seminal iron. Infertile men with varicocele have seminal lactoferrin levels comparable to other infertile men and possibly fertile individuals. Iron concentrations are not linked to lactoferrin levels in seminal plasma.

Study for the Significance of Ascetic Fluid Lactoferrin in Diagnosis of Spontaneous Bacterial Peritonitis in Decompensated Liver Cirrhosis

Abstract Background Cirrhosis represents the inal common histological pathway for a wide variety of chronic liver diseases. Occurrence of ascites is the most common presentation of liver cirrhosis. Spontaneous bacterial peritonitis (SBP) is observed in 15–26% of patients hospitalized with ascites. SBP is deined as the infection of AF in the absence of a contiguous source of infection and/or an intra-abdominal inlammatory focus. An AF-polymorphonuclear (PMN) leukocyte count more than or equal to 250/mm irrespective of the AF culture result is universally accepted nowadays as the best surrogate marker for diagnosing SBP. Frequently, the results of the manual or automated PMN count do not reach the hands of the responsible medical personnel in a timely manner. Aim of the Work to use AF lactoferrin for the diagnosis of SBP and to identify a clinically useful marker that can be used for future development of an important clinical, economic, and time saving rapid bedside test for the diagnosis of SBP in cirrhotic ascites. Patients and Methods This study was conducted on 60 patients with decompensated chronic liver disease and ascites with and without spontaneous bacterial peritonitis admitted to Gastroenterology and Hepatology department inpatient and outpatient clinics at Ain Shams University Hospitals and labs, from April 2023 to September 2023. Results Females were affected more than males by SBP, SBP has higher incidence in elderly compared to control group No significant difference between studied groups regards to risk factors and Child class (p &amp;gt; 0.05). HCV infection was the main etiology of liver cirrhosis in both groups while HBV infection was much less common with no significant difference between studied groups (p &amp;gt; 0.05). Patients in SBP group showed positive reaction to CRP compared to control group with significant difference between them (p &amp;lt; 0.05). No statistical significant differences between studied groups regards to abdominal ultrasonographic indings (p &amp;gt; 0.05). Liver enzymes (ALT and AST) were higher in SBP patients compared to non SBP patients with signiicant difference between them (P &amp;lt; 0.05). SBP patients have higher TLC and lower MCV and platelets count compared to non SBP patients with signiicant difference between them (P &amp;lt; 0.05). No statistical signiicant difference between studied groups regards to INR, Hb and MCH values (p &amp;gt; 0.05). Conclusion Outcomes of our study provide evidence of the clinical usefulness of AF lactoferrin levels in patients with cirrhosis to differentiate those with and without SBP. It is important to note that the correlation of lactoferrin levels and inlammatory markers in blood samples and AF could be inluenced by lysis of PMN cells during transport to the laboratory, which could lead to a false negative result. Moreover, manual measurement of the AF and PMN count is operator dependent, which makes quality control difficult. Commercially available kits for the measurement ascetic luid lactoferrin could be used in a future development of qualitative bedside assay.

Lactoferrin in Pediatric Chronic Kidney Disease and Its Relationship with Cardiovascular Risk.

Pediatric CKD is associated with a high risk of cardiovascular disease (CVD). Early detection of subclinical CVD in childhood CKD can be achieved through various cardiovascular (CV) assessments, including carotid intima-media thickness (cIMT), ambulatory blood pressure monitoring (ABPM), and arterial stiffness indices. Lactoferrin (LF), a key functional glycoprotein found in breast milk, has been linked to several diseases and has potential as a biomarker. In our study of 102 children with CKD stages G1-G4, we explored the relationship between LF and CV risk markers. We found that LF concentration was not related to the severity or underlying causes of childhood CKD, but was positively correlated with overweight/obesity. Lower LF levels were correlated with increased cIMT and elevated arterial stiffness indices. Notably, abnormalities in ABPM profiles were observed in up to 60% of the children with CKD, with low LF levels linked to nighttime hypertension, nocturnal non-dipping, and ABPM abnormalities. In conclusion, LF shows promise as a biomarker for detecting subclinical CVD in children with CKD. Its potential utility in early detection could be instrumental in guiding timely interventions and improving long-term CV outcomes, although further research is needed to clarify the underlying mechanisms.

Human transferrin and lactoferrin cooperatively support Neisseria meningitidis colonization in the murine nasopharynx.

Neisseria meningitidis is a human-restricted bacteria that is a normal nasopharyngeal resident, yet it can also disseminate, causing invasive meningococcal disease. Meningococci are highly adapted to life in humans, with human-specific virulence factors contributing to bacterial adhesion, nutrient acquisition and immune evasion. While these factors have been explored in isolation, their relative contribution during infection has not been considered due to their absence in small animal models and their expression by different human cell types not readily combined in either in vitro or ex vivo systems. Herein, we show that transgenic expression of the iron-binding glycoproteins human transferrin and lactoferrin can each facilitate N. meningitidis replication in mouse serum but that transferrin was required to support infection-induced sepsis. While these host proteins are insufficient to allow nasopharyngeal colonization alone, mice co-expressing these and human CEACAM1 support robust colonization. In this case, meningococcal colonization elicits an acute elevation in both transferrin and lactoferrin levels within the upper respiratory mucosa, with transferrin levels remaining elevated while lactoferrin returns to basal levels after establishment of infection. Competitive infection of triple transgenic animals with transferrin- and lactoferrin- binding protein mutants selects for bacteria expressing the transferrin receptor, implicating the critical contribution of transferrin-based iron acquisition to support colonization. These transgenic animals have thus allowed us to disentangle the relative contribution of three virulence factors during colonization and invasive disease, and provides a novel in vivo model that can support extended meningococcal colonization, opening a new avenue to explore the meningococcal lifestyle within its primary niche.

The Effect of the Season on the Time Dependent Changes in Colostrum Lactoferrin Level in Murciano-Granadina Goats in Intensive System Farming.

The aim of this research was to evaluate the effects of postpartum day and parity season on the lactoferrin (LF), immunoglobulin G (IgG), and chemical composition of Murciano-Granadina goat colostrum during the first 96 h after kidding, and the use of the Brix refractometer to estimate IgG content. A herd of 3500 intensively managed Murciano-Granadina dairy goats (45-50 kg body weight) was used. Colostrum samples were collected from days 1 to 4 postpartum in the winter, spring, summer, and autumn. The colostrum composition was assessed using an automated infrared method; the LF and IgG concentrations were measured using an ELISA, and for the Brix percentage, we used a digital refractometer. Colostrum taken on the first postpartum day showed the highest concentrations of LF, IgG, proteins and non-fat solids (NFSs). As the postpartum days progressed, a rapid decrease in the LF, IgG, protein, and NFS contents and the Brix value was observed. In contrast, the lactose content increased steadily until the fourth postpartum day (p < 0.001). The season influenced milk yield, LF, IgG, protein, fat, and somatic cell content (p < 0.05). LF contents were significantly higher in the spring season, IgG contents were higher in autumn colostrum, and fat components were higher in the winter season. The colostrum Brix value showed a positive correlation with the ELISA colostrum LF (r = 0.716, p < 0.001) and IgG (r = 0.894, p < 0.001) determination; a 20 mg IgG/mL colostrum concentration corresponded to 18 °Brix. Our results corroborate the importance of feeding colostrum to newborns on the first day after birth, not only because of its high level of IgG but also because of its greater presence of the other bioactive protein compounds such as lactoferrin.

Impact of Hypoxia on Neutrophil Degranulation and Inflammatory Response in Alpha-1 Antitrypsin Deficiency Patients.

Alpha-1 antitrypsin deficiency (AATD) is an inflammatory disorder where neutrophils play a key role. Excessive neutrophil activation leads to local hypoxia and tissue damage. Most research on neutrophil function has been conducted under atmospheric conditions (21% O2), which may not represent physiological or pathological conditions. This study aimed to determine the effects of hypoxia on neutrophil degranulation and cytokine production in AATD patients. Neutrophils isolated from 54 AATD patients (31 MZ; 8 SZ; 15 ZZ) and 7 controls (MM) were exposed to hypoxia (1% O2) for 4 h. Neutrophil degranulation was assessed by measuring elastase (NE), myeloperoxidase (MPO), lactoferrin, and matrix metalloproteinase-9 (MMP-9) levels using immunoassay-based methods. Pro-inflammatory (IL-8, IL-1 beta, IL-6, and TNF-alpha) and anti-inflammatory (IL-4 and IL-10) cytokine levels were assessed by a Luminex-based method. Our results indicate a significantly increased release of NE (p = 0.015), MPO (p = 0.042), lactoferrin (p = 0.015), and MMP-9 (p = 0.001) compared to controls. Pro-inflammatory cytokines show a significant rise in IL-8 (p = 0.019), a trend towards increased IL-1 beta (p = 0.3196), no change in IL-6 (p = 0.7329), and reduced TNF-alpha (p = 0.006). Anti-inflammatory cytokines show increased IL-4 (p = 0.057) and decreased IL-10 (p = 0.05703). Increased neutrophil degranulation and inflammatory phenotype are observed in AATD neutrophils under physiological hypoxia.

Increased Intestinal Inflammation and Permeability in Glaucoma.

Evidence suggests that dysbiosis of the gut microbiota plays a pivotal role in the development of glaucoma. This dysbiosis is commonly associated with chronic intestinal inflammation and increased intestinal permeability. However, the understanding of intestinal inflammation and permeability in glaucoma remains insufficient. This study aims to investigate the potential relationship between fecal inflammation and permeability markers and glaucoma. We recruited 114 glaucoma patients and 75healthy controls. Levels of fecal lactoferrin (Lf) and alpha-1 antitrypsin (AAT) were quantified using enzyme linked immunosorbent assay (ELISA) to compare both biomarkers between groups and across different severity grades of glaucoma. Logistic regression analysis was used to assess the association between these fecal biomarkers and glaucoma. The severity of glaucoma was assessed based on the mean deviation (MD) in the visual field. In this study, we observed elevated levels of fecal Lf and AAT in glaucoma patients. The proportion of glaucoma patients with abnormal fecal Lf levels (≥ 7.25µg/g) was significantly higher than that of the controls (p = 0.012). A positive correlation was noted between fecal Lf and AAT (rho = 0.20, p = 0.006). After adjusting for age and sex, multivariable logistic regression analysis indicated that both fecal Lf (OR = 1.11, 95% CI: 1.01-1.21, p = 0.026) and AAT (OR = 1.01, 95% CI: 1.01-1.02, p < 0.001) positively correlated with glaucoma. These biomarkers might reflect glaucoma severity, with significant differences in fecal Lf levels observed between moderate and severe stages, but not in the early stage. Furthermore, increasing levels of fecal AAT correlated with greater severity of glaucomatous injury and a larger vertical cup-to-disc ratio (VCDR) (p < 0.05). This study suggests an increase in intestinal inflammation and permeability in glaucoma, further indicating the importance of the 'gut-retina axis' in the pathogenesis of the disease and potentially offering new therapeutic avenues.

Acute salivary antimicrobial peptide secretion response to different exercise intensities and durations.

Antimicrobial peptides, key players of innate mucosal immunity in the oral cavity, exert antibacterial and bacteriolytic effects. This study aimed to clarify the effects of acute exercise at different intensities and durations on salivary antimicrobial peptide levels. In a randomized crossover trial, 14 young healthy untrained men performed intensity trials [cycling at 35%, 55%, and 75% of maximal oxygen uptake (V̇o2max) for 30 min] and duration trials (cycling at 55% V̇o2max for 30, 60, and 90 min). Saliva samples were collected at baseline and 0 and 60 min after exercise. In intensity trials, the change in salivary lactoferrin levels from baseline to 0 min after 30 min exercise was greater at 75% V̇o2max exercise intensity compared with that at 35% V̇o2max. Furthermore, the change in salivary human β-defensin-2 (HBD-2) levels was greater at 75% V̇o2max compared with that at 35% and 55% V̇o2max. Salivary lysozyme levels increased after exercise, independent of exercise intensity. However, salivary LL-37 levels did not change after exercise at any intensity. In addition, in duration trials, the change in salivary levels of LL-37 and HBD-2 from baseline to 0 min after exercise at 55% V̇o2max was greater after 60 and 90 min of exercise compared with that after 30 min of exercise. However, salivary lactoferrin and lysozyme levels increased after exercise, independent of exercise duration. Our findings suggest that secretory responses to acute exercise with exercise intensity and duration differ among salivary antimicrobial peptides.NEW & NOTEWORTHY We investigated the effects of acute exercise at different intensities and durations on the immune response to salivary antimicrobial peptides in young healthy men. Levels of four salivary antimicrobial peptides increased after exercise dependently or independently of exercise intensity and duration, whereas some salivary antimicrobial peptides did not change after exercise. These findings suggest that the secretory responses to acute exercise with different intensities and durations differ among salivary antimicrobial peptides.

Fluorescence-based reagent and spectrum-based optical reader for lactoferrin detection in tears: differentiating Sjögren’s syndrome from non-Sjögren’s dry eye syndrome

Identification of an early biomarker and effective testing device to differentiate dry eye disease secondary to autoimmune disease (Sjögren’s syndrome dry eye disease) from non-Sjögren’s dry eye disease are prerequisites for appropriate treatment. We aimed to demonstrate the capacity of a new photo-detection device to evaluate tear lactoferrin levels as a tool for differentiating systemic conditions associated with dry eye disease. Patients with non-Sjögren’s and Sjögren’s syndrome dry eye disease (n = 54 and n = 52, respectively) and controls (n = 11) were enrolled. All participants completed the Ocular Surface Disease Index questionnaire. Tear collection was performed with Schirmer test, and tear break-up time was examined using a slit lamp. Tear lactoferrin was evaluated using our newly developed photo-detection device. The average lactoferrin concentration was significantly lower in samples from patients with non-Sjögren’s dry eye disease (0.337 ± 0.227 mg/mL, n = 54) and Sjögren’s syndrome dry eye disease (0.087 ± 0.010 mg/mL, n = 52) than in control samples (1.272 ± 0.54 mg/mL, n = 11) (p < 0.0001). Further, lactoferrin levels were lower in patients with Sjögren’s syndrome dry eye disease than in those with non-Sjögren’s dry eye disease (p < 0.001). Our cost-effective, antibody-free, highly sensitive photo-detection device for evaluating tear lactoferrin levels can assist ophthalmologists in differentiating different types of dry eye diseases.

The BLV-miRNAs pathway of BLV inhibits the expression of Lactoferrin, Lactoperoxidase, Alpha-lactalbumin and Beta-lactoglobulin proteins

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.

Clinical performance of fecal calprotectin, lactoferrin, and hemoglobin for evaluating the disease activity of IBD and detecting colorectal tumors.

Recently, noninvasive fecal markers have been used as indicators of intestinal inflammation in patients with inflammatory bowel disease (IBD). We conducted a clinical validation study to measure fecal calprotectin (Cp), lactoferrin (Lf), and hemoglobin (Hb) levels using an all-in-one kit in patients with IBD and colorectal tumors and aimed to clarify the utility of these fecal markers. In this study, 104 patients were analyzed, including 25 patients with ulcerative colitis (UC), 20 with Crohn's disease (CD), 48 with colorectal tumors, and 13 healthy controls (HC). Of the 48 patients with colorectal tumors, 14 had invasive cancer. We validated the utility of fecal Cp, Lf, and Hb levels by simultaneously measuring fecal markers in patients with IBD and colorectal tumors. Fecal Cp and Lf had almost equivalent abilities in detecting clinical remission in patients with UC; however, fecal Cp was slightly superior to Lf. Regarding colorectal tumors, fecal Cp and Lf levels tended to be higher in patients with adenomas and colorectal cancer than in HCs. Although fecal Hb alone had the best sensitivity and specificity for detecting colorectal cancer, it had relatively low sensitivity for detecting advanced neoplasms and colorectal cancer. Fecal Cp and Lf can be used as almost equivalent biomarkers to assess the clinical activity in patients with UC. Fecal Hb is the most useful marker for screening colorectal cancer; however, adding fecal Cp and Lf may compensate for the low sensitivity of detecting for advanced colorectal tumors based on Hb alone.

Application of pressure homogenization on whole human milk pasteurized by high hydrostatic pressure: Effect on protein aggregates in milk fat globule membrane and skim milk phases

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.

LTF as a Potential Prognostic and Immunological Biomarker in Glioblastoma.

The lactoferrin (LTF) gene behaves like a tumor suppressor gene in diverse tumors, such as renal cancer, nasopharyngeal carcinoma and gastric cancer. However, the prognostic value of LTF expression in patients with glioblastoma remains unclear. In this study, the expression levels of LTF in patients with GBM were investigated in TCGA, GEPIA, CGGA and GEO database, and a survival analysis of LTF based on TCGA and CGGA was performed. Furthermore, the present study demonstrated the LTF gene co-expression, PPI network, KEGG/GO enrichment and immune cell infiltration analysis on TCGA and TIMER2.0 database. We found that LTF expression was significantly upregulated in GBM samples compared with normal samples and other glioma samples, and Kaplan-Meier analysis demonstrated that the overexpression of LTF were significantly associated with worse overall survival (OS) and 5-year OS in GBM patients (P < 0.05). KEGG/GO enrichment analysis demonstrated that functions of LTF concentrated in immune and inflammatory response and peptidase regulation (P < 0.05). Immune cell infiltration analysis presented that high LTF expression exhibited dysregulated immune infiltration (i.e., CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells and cancer associated fibroblast). LTF was upregulated in tumors and correlated with worse OS in GBM patients, and LTF might function as an oncogene via inducing dysregulated immune infiltration in GBM.