Gestational Diabetes Mellitus and Colostral Appetite-Regulating Adipokines.

Gestational diabetes mellitus (GDM) is a complex metabolic disorder that has short- and long-term effects on maternal and offspring health. This study aimed to assess the impact of maternal hyperglycemia severity, classified as GDM-G1 (diet treatment) and GDM-G2 (insulin treatment) on colostral appetite-regulating molecules. Colostrum samples were collected from hyperglycemic (N = 30) and normoglycemic (N = 21) mothers, and the concentrations of milk hormones were determined by immunoenzymatic assay. A difference was found for milk ghrelin, but not for molecules such as adiponectin, leptin, resistin, or IGF-I levels, in relation to maternal hyperglycemia. The colostral ghrelin in the GDM-G1 cohort (0.21 ng/mL) was significantly lower than for GDM-G2 (0.38 ng/mL) and non-GDM groups (0.36 ng/mL). However, colostral resistin was higher, but not significantly, for GDM-G1 (13.33 ng/mL) and GDM-G2 (12.81 ng/mL) cohorts than for normoglycemic mothers (7.89 ng/mL). The lack of difference in relation to hyperglycemia for milk leptin, adiponectin, leptin-adiponectin ratio, resistin, and IGF-I levels might be the outcome of effective treatment of GDM during pregnancy. The shift between ghrelin and other appetite-regulating hormones might translate into altered ability to regulate energy balance, affecting offspring's metabolic homeostasis.

The Difference of Milk-Derived Extracellular Vesicles from Cow Colostrum and Mature Milk on miRNAs Expression and Protecting Intestinal Epithelial Cells against Lipopolysaccharide Damage.

Intestinal epithelial cells (IECs) play crucial roles in forming an essential barrier, providing host defense against pathogens and regulating nutrients absorption. Milk-derived extracellular vesicles (EVs) within its miRNAs are capable of modulating the recipient cell function. However, the differences between colostrum and mature milk EVs and their biological function in attenuating intestinal epithelial cell injury remain poorly understood. Thus, we carried out the present study to characterize the difference between colostrum and mature milk-derived miRNA of EVs and the effect of colostrum and mature milk EVs on the proliferation, apoptosis, proinflammatory cytokines and intestinal epithelial barrier related genes in IEC-6 induced by LPS. Differential expression of 329 miRNAs was identified between colostrum and mature milk EVs, with 185 miRNAs being downregulated and 144 upregulated. In addition, colostrum contains a greater number and protein concentration of EVs than mature milk. Furthermore, compared to control, EVs derived from colostrum significantly inhibited the expression of apoptosis- (Bax, p53, and caspase-3) and proinflammatory-related genes (TNFα, IL6, and IL1ß). EVs derived from mature milk did not affect expression of apoptosis-related genes (Bax, p53, bcl2, and caspase-3). The EVs derived from mature milk significantly inhibited the expression of proinflammatory-related genes (TNFα and IL6). Western blot analysis also indicated that colostrum and mature milk EVs significantly decreased the apoptosis of IEC-6 cells. The EdU assay results showed that colostrum and mature milk EVs significantly increased the proliferation of IEC-6 cells. The expression of intestinal barrier-related genes (TJP1, CLDN1, OCLN, CDX2, MUC2, and IGF1R) was significantly promoted in IEC-6 cells after colostrum and mature milk EVs addition. Importantly, colostrum and mature milk EVs significantly relieved the LPS-induced inhibition of proliferation and intestinal barrier-related genes expression and attenuated apoptosis and proinflammatory responses induced by LPS in IEC-6 cells. Flow cytometry and Western blot analysis also indicated that colostrum and mature milk EVs significantly affect the apoptosis of IEC-6 cells induced by LPS. The results also indicated that EVs derived from colostrum had better effects on inhibiting the apoptosis- and proinflammatory cytokines-related genes expression. However, the EVs derived from mature milk exhibited beneficial effects on intestinal epithelial barrier protection. The present study will provide a better understanding of the role of EVs derived from colostrum and milk in dairy cows with different responses in the regulation of intestinal cells function, and also presents new evidence for the change of EVs cargos during various stages of lactation.

Effects of Dietary Colostrum Basic Protein on Bone Growth and Calcium Absorption in Mice.

Colostrum basic protein (CBP) is a trace protein extracted from bovine colostrum. Previous studies have shown that CBP can promote bone cell differentiation and increase bone density. However, the mechanism by which CBP promotes bone activity remains unclear. This study investigated the mechanism of the effect of CBP on bone growth in mice following dietary supplementation of CBP at doses that included 0.015%, 0.15%, 1.5%, and 5%. Compared with mice fed a normal diet, feeding 5% CBP significantly enhanced bone rigidity and improved the microstructure of bone trabeculae. Five-percent CBP intake triggered significant positive regulation of calcium metabolism in the direction of bone calcium accumulation. The expression levels of paracellular calcium transport proteins CLDN2 and CLDN12 were upregulated nearly 1.5-fold by 5% CBP. We conclude that CBP promotes calcium absorption in mice by upregulating the expression of the calcium-transporting paracellular proteins CLND2 and CLND12, thereby increasing bone density and promoting bone growth. Overall, CBP contributes to bone growth by affecting calcium metabolism.

Buffalo colostrum peptide mitigates Parkinson's disease pathophysiology through Cullin-3 inhibition.

Colostrum/Milk is a chief repertoire of antioxidant peptides. Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a viable target for Parkinson's Disease (PD), as this pathway deduced to be impaired in PD. Cullin-3 is one of the crucial E3 ligase responsible for its regulation. The present study screened peptide libraries of buffalo colostrum & milk peptides for Cullin-3 inhibition, thus ensuing activation of Nrf2 to alleviate the molecular etiopathology in PD using the C. elegans as a model. The structure was modelled, binding sites analyzed and peptide-interactions analyzed by docking. Among the 55 sequences (≤1 kDa), the peptide SFVSEVPEL having the highest dock score (-16.919) was synthesized and evaluated for its effects on oxidative stress markers, antioxidant enzymes, neurochemical marker and Nrf2/Skn-1 levels. The lead peptide alleviated the oxidative pathophysiology and behavioural deficits associated with PD in C. elegans.

Initial diet shapes resistance-gene composition and fecal microbiome dynamics in young ruminants during nursing.

This study was conducted to examine how colostrum pasteurization affects resistance genes and microbial communities in calf feces. Forty female Holstein calves were randomly assigned to either the control (CON) group, which received unheated colostrum, or the pasteurized colostrum (PAT) group. The calves body weight was measured weekly before morning feeding. Calf starter intake were measured and recorded daily before morning feeding. Samples of colostrum were collected before feeding. Blood was collected on d 1 and 70 before morning feeding. Ten calves were randomly selected from each group (n = 20 calves total) for fecal sampling on d 3, 28, 56 and 70 for subsequent DNA extraction and metagenomic sequencing. Total bacterial counts in the colostrum were markedly higher in the CON group than in the PAT group. Pasteurized colostrum administration substantially reduced the ARO diversity and diminishes the abundance of Enterobacteriaceae, thereby decreasing their contribution to resistance genes. Pasteurization also reduced glucoside hydrolase-66 activity in 3-day-old calves which led to an increase in the activity of aminoglycoside antibiotics, resulting in 52.63 % of PAT-enriched bacteria acquiring aminoglycoside resistance genes. However, from the perspective of overall microbial community, the proportion of aminoglycoside, beta-lactam and tetracycline resistance genes carried by microbial community in PAT group was lower than CON group (P < 0.05). Fecal samples from the PAT group contained greater abundances of Subdoligranulum (P < 0.05) and Lachnospiraceae_NK4A136_group (P < 0.05) on days 28 and 70 compared to CON. Network analysis and abundance variations of the different bacteria obtained by linear discriminant analysis effect size analysis showed that pasteurized colostrum feeding reduced the interactions among related bacteria and maintained stability of the hind-gut microbiome. In conclusion, these findings underscore the intricate interactions between early diet, calf resistance-gene transmission and microbial dynamics, which should be carefully considered in calf-rearing practices.

Phosphoproteomics Revealed Differentially Expressed Sites and Function of the Bovine Milk Fat Globule Membrane in Colostrum and Mature Milk.

One type of large and intricate post-translational modification of milk proteins that has significant biological implications is phosphorylation. The characterization of phosphoproteins found in the bovine milk fat globule membrane (MFGM) is still mostly unknown. Here, label-free phosphoproteomics was used to identify 94 phosphorylation sites from 54 MFGM phosphoproteins in bovine colostrum (BC) and 136 phosphorylation sites from 91 MFGM phosphoproteins in bovine mature milk (BM). αs1-Casein and ß-casein were the most phosphorylated proteins in bovine colostrum. In bovine mature milk, perilipin-2 was the protein with the greatest number of phosphorylation sites. The results show that bovine colostrum MFGM phosphoproteins were mainly involved in immune function, whereas bovine mature MFGM phosphoproteins were mainly involved in metabolic function. Plasminogen and osteopontin were the most strongly interacting proteins in colostrum, whereas perilipin-2 was the most strongly interacting protein in bovine mature milk. This work demonstrates the unique alterations in the phosphorylation manner of the bovine MFGM protein during lactation and further expands our knowledge of the site characteristics of bovine MFGM phosphoproteins. This result confirms the value of MFGM as a reference ingredient for infant formula during different stages.

Enrichment of medium-quality colostrum by adding colostrum replacer, combined or not with transition milk in the feeding of dairy calves.

Fifty Holstein calves were allocated in randomized blocks and distributed in a 2 × 2 factorial arrangement; (A) two sources of Ig: (1) Control: bovine colostrum (25% Brix); (2) Enriched colostrum: mid-quality bovine colostrum (20% Brix) enriched with colostrum replacer to 25% Brix; and (B) two transition feeding diets: (1) Whole milk (WM): supply of 4 L/day of whole milk for 3 days after the colostrum feeding; and (2) Formulated transition milk (FTM): supply 4 L/day of whole milk enriched with 70 g/L of colostrum replacer for 3 days after the colostrum feeding. Blood samples were collected at 0, 24, 48, and 72 h of age to determine total serum protein (TSP), glucose, non-esterified fatty acids (NEFA), erythrocyte and leukocyte concentrations. IgG was measured at 48 h. During the preweaning period, calves received 6 L/day of whole milk. Blood samples were collected weekly to determine TSP, glucose, and lactate. The colostrum protocols were equally efficient for transfer of passive immunity with IgG concentration at 48 h ≥ 49.6 g/L. Colostrum or transition feeding program did not influence the erythrocyte and leukocyte concentrations. The TSP concentration measured until 72 h was higher for calves fed maternal colostrum. Calves fed milk in the transition period had higher glucose concentrations. Calves receiving bovine colostrum and FTM had higher glucose concentrations in the preweaning period, while the enriched colostrum decreased plasma lactate concentrations. In summary, enrichment of mid-quality colostrum is an alternative in situations of a shortage of high-quality colostrum; however, feeding 4 L/day of FTM only for 3 days after colostrum feeding does not show additional benefits.

Impacts of preweaning colostrum feeding practices and health measures on dairy cow production, while accounting for genetic potential.

Calf management and health are essential for setting up the foundation of a productive cow. The objectives of this study were to estimate the impact of preweaning practices on milk production parameters while accounting for an animal's genetic potential in New Brunswick, Canada. A retrospective cohort study was performed on 220 heifer calves from eight herds born in 2014-2015. Preweaning practices and health data were recorded by producers and reviewed by the herd veterinarian for each calf. The herd veterinarian also visited the farms to collect serum samples from calves and frozen colostrum samples. The production outcomes assessed were milk, protein and fat yields, standardized to 305 d for the first lactation (L1) and a combined group of lactations two and three (L2 + 3). The genomic potential was determined as genomic parent averages (GPA) for the associated production parameters. Analysis was performed with multivariable linear (L1) and linear mixed (L2 + 3) regression models. In L1, for every 1.0 kg increase in weaning weight, milk, protein, and fat yield increased by 25.5, 0.82, and 1.01 kg, respectively (P < 0.006). Colostrum feeding time (CFT) positively impacted L1 milk and protein production, with feeding between 1-2 h of life producing the greatest estimates of 626 kg of milk and 18.2 kg of protein yield (P < 0.007), compared to earlier or later CFT. Fat yield production was decreased by 80.5 kg (P < 0.006) in L1 when evaluating animals that developed a preweaning disease and were not treated with antibiotics compared to healthy untreated animals. Impacts on L2 + 3 were similar across all production outcomes, with a positive interaction effect of CFT and weaning weight. Compared to CFT < 1 h, the later CFT groups of 1-2 h and > 2 h produced greater yield outcomes of 68.2 to 72.6 kg for milk (P < 0.006), 2.06 to 2.15 kg for protein (P < 0.005), and 1.8 to 1.9 kg for fat (P < 0.045) for every 1 kg increase of weaning weight, respectively. The fit of all models was significantly improved with the inclusion of GPA. These results indicate that colostrum management and preweaning health measures impacted production parameters as adults. The inclusion of GPA significantly improved the accuracy of the models, indicating that this can be an important parameter to include in future studies.

The impact of calf management and health events have been predominately investigated during the preweaning period. However, calfhood events could also impact the animal's health and productivity as an adult. Results from this study indicate that colostrum feeding time and weaning weight were associated with production outcomes (milk, protein, and fat yields) across the first three lactations, and disease and antibiotic treatment can be detrimental to fat yield in the first lactation. By including genetic potential in the assessment of preweaning colostrum practices and health measures on production outcomes, we can more precisely identify areas to optimize calf management.

Biochemical properties of sheep colostrum and its potential benefits for lamb survival: a review.

Colostrum is the initial secretion of the mammary glands following parturition, which offers main food, protection, and biological active substances for the new born. The most threatening episode of neonate's life is the initial two weeks after birth. This period is associated with high neonatal mortality and morbidity. These worthwhile losses lead to a poor prolificacy rate, low profitability, and ultimately poor performance in animal production. Hence, both diseases and mortality cause valuable losses in terms of production and economic losses. The survival of neonate is correlated with their immune status and passive immune transfer (PIT). Colostrum provides the primary source of nutrition and immunity (PIT) that protects neonates against infections. It must be given as soon as possible after birth since its immunoglobulins are absorbed within the first 16-27 hours after birth, ideally within 2-4 hours. As a result, immunoglobulin (PIT) is the most important component of distressing infectious immunity, and a passable concentration of immunoglobulin in the blood of newborn lambs is linked to their health and survival rate. In this review, we summarized the importance of colostrum in early life and its association with neonatal lamb's survival, profitability and productivity of sheep farming.

The effects of feeding sows at onset of farrowing supplemental energy (blend of carbohydrates and glycerol) on farrowing kinetics and piglet vitality.

Delivering piglets is one of the most energy-demanding activities sows undergo in their lifetime. Sows can have myometrial contractions from 2 to 12 h before the first piglet is expelled as well as a nest-building behavior. Thus, when the first piglet is delivered, the female has already used part of her energy supply. When the sow gets exhausted due to lack of energy, the farrowing process can be interrupted, causing damage to the viability and vitality of the piglets. In the present study, we evaluated the effects of feeding sows an energy supplement at the onset of farrowing on farrowing kinetics and piglet vitality. The energy supplement consisted of a blend of carbohydrates and glycerol which provides 439 kJ of metabolizable energy per kg of metabolic weight. A total of 180 sows were used. At the onset of farrowing, sows were assigned to one of the following treatments: sows that were not supplied energy at the onset of farrowing, serving as controls (CON, n = 85); sows fed the energy supplement at the onset of farrowing (ESP, n = 95). Farrowing kinetics, blood glucose concentration, and piglet vitality were recorded for each sow. Blood glucose concentration was assessed by puncturing the auricular vein and using a portable glucometer at four different time points: after the birth of the 1st piglet (T0), and at 20 (T20), 40 (T40), 80 (T80), and 180 (T180) min after the birth of the 1st piglet. The vitality of the 1st, 6th, 12th, 17th, and 20th piglet born was evaluated using the Apgar score. Piglet birth weight and average colostrum intake were measured. The farrowing duration was 20 min shorter (P < 0.05) for ESP sows in comparison with CON sows. Sows from ESP treatment had higher (P ≤ 0.05) blood glucose concentration at T20 and T40 compared to the CON sows. The inter-piglet birth interval was shortened (P < 0.05) by 14 min between the 1st and 2nd piglet for the ESP treatment. The 17th and 20th piglets born from ESP sows had higher (P < 0.05) Apgar score compared to piglets of the same birth order from CON sows. Colostrum intake was higher (P < 0.01) for piglets born from ESP sows. Litter growth performance did not differ (P > 0.05). In conclusion, feeding a blend of carbohydrates and glycerol as an energy supplement for farrowing sows improved farrowing kinetics and piglet vitality score.

Bisphenol chemicals in colostrum from Shanghai, China during 2006-2019: Concentration, temporal variation, and potential influence on birth parameters.

Bisphenol A (BPA) and its alternatives bisphenol S (BPS) and bisphenol F (BPF) are identified as endocrine disruptors that have negative impacts on infant growth. Their temporal variations in human milk and potential effects on fetal growth are not well known. In this study, colostrum collecting at four time points between 2006 and 2019 and paired urine in 2019 from Shanghai, China, were analyzed for eight bisphenols. The total concentrations in colostrum in 2019 were up to 3.43 ng/mL, with BPA being dominant, followed by BPS and BPF. BPA levels in colostrum noticeably decreased from 2010 to 2013. Additionally, obvious percentage changes in bisphenols were observed in 2019. The BPA concentrations in paired colostrum and urine were not significantly correlated. High levels of BPA in colostrum were linked to a significant reduction in birth head circumference in 2019 (p = 0.031). BPA and BPS in colostrum might have similar negative effect on fetal growth in 2019, but these effects were generally non-significant. Further studies are needed to testify the potential impact. The hazard indexes for infants in the first week of life were below 1, suggesting no obvious health risks. However, the high contribution from BPA still warrants further attention.

Relationship Between Maternal Age and Macronutrient Content of Colostrum.

BACKGROUND: Little is known about the relationship between maternal age and the macronutrient content of colostrum. RESEARCH AIMS: This study aimed to evaluate the relationship between maternal age and human milk macronutrient content by comparing the concentrations of lactose, proteins, and lipids in the colostrum of women with younger, moderate, and advanced maternal age. METHODS: An observational, cross-sectional study was designed to compare the macronutrient concentrations in the colostrum of women aged < 20 years, 20 to 34 years, and > 34 years (younger, moderate, and advanced maternal age, respectively; n = 33 per group). For each participant, 3 ml of colostrum was collected by manual extraction from the right breast at 10 am, 39-48 hr after delivery, and analyzed using a Miris Human Milk Analyzer. Macronutrient concentrations were compared between the groups using analysis of variance. P < 0.05 was considered significant. RESULTS: Mothers with moderate maternal age had a higher colostrum lipid concentration than those with younger or advanced maternal age (2.3 mg, SD = 1.4 mg vs. 1.5 mg, SD = 1.0 mg vs. 1.6 mg, SD = 0.9 mg, respectively; p = 0.007). Lactose and protein contents in the analyzed samples did not differ among the three study groups. CONCLUSION: This study lends support to the potential variation of lipids in colostrum by maternal age and suggests individual adaptation to the nutritional components of milk to the needs of the infant may be beneficial.

Effect of oropharyngeal colostrum therapy on neonatal sepsis in preterm neonates: A systematic review and meta-analysis.

Various studies have shown that oropharyngeal colostrum application (OPCA) is beneficial to preterm neonates. We performed a systematic review and meta-analysis to assess whether OPCA reduces the incidence of culture-proven neonatal sepsis in preterm neonates. Randomized controlled trials comparing OPCA with placebo or standard care in preterm neonates were included. Medline, Embase, Web of Science, Cumulated Index to Nursing and Allied Health Literature, Scopus, and CENTRAL were searched for studies published up to June 15, 2023. We used the Cochrane Risk of Bias tool, version 2, for risk of bias assessment, the random-effects model (RevMan 5.4) for meta-analysis, and Gradepro software for assessing the certainty of evidence. Twenty-one studies involving 2393 participants were included in this meta-analysis. Four studies had a low risk of bias, whereas seven had a high risk. Oropharyngeal colostrum significantly reduced the incidence of culture-proven sepsis (18 studies, 1990 neonates, risk ratio [RR]: 0.78, 95% confidence interval [95% CI]: 0.65, 0.94), mortality (18 studies, 2117 neonates, RR: 0.73, 95% CI: 0.59, 0.90), necrotizing enterocolitis (NEC) (17 studies, 1692 neonates, RR: 0.59, 95% CI: 0.43, 0.82), feeding intolerance episodes (four studies, 445 neonates, RR: 0.59, 95% CI: 0.38, 0.92), and the time to full enteral feeding (19 studies, 2142 neonates, mean difference: -2 to 21 days, 95% CI: -3.44, -0.99 days). There was no reduction in intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, ventilator-associated pneumonia, neurodevelopmental abnormalities, hospital stay duration, time to full oral feeding, weight at discharge, pneumonia, and duration of antibiotic therapy. The certainty of the evidence was high for the outcomes of culture-positive sepsis and mortality, moderate for NEC, low for time to full enteral feeding, and very low for feeding intolerance. OPCA reduces culture-positive sepsis and mortality (high certainty), NEC (moderate certainty), and time to full enteral feeding (low certainty) in preterm neonates. However, scarcity of data from extremely premature infants limits the generalizability of these results to this population.

The influence of parity, body condition, litter size and carbetocin administration on colostrum production and immunoglobulin levels in highly productive sows within a tropical environment.

The aim of this study was to explore the factors contributing to colostrum production and the levels of colostrum immunoglobulins (IgG and IgA) in contemporary highly productive sows within a tropical climate. We focused on variables such as parity number, litter size, sow body condition score (BCS), the timing of sample collection following the commencement of farrowing and the use of carbetocin during the birthing process. A total of 100 colostrum samples were collected from a group of 50 Danish Landrace × Yorkshire crossbred sows. These samples were taken at two distinct time intervals: right after farrowing (0 h) and 6 h later. The colostrum samples were classified according to the sows' parity numbers, with 33 samples originating from primiparous sows and 67 from multiparous ones. Additionally, the number of live-born piglets were categorized into three groups: 7-13, 14-17 and ≥ 18 piglets per litter. Moreover, the samples were categorized based on the use of carbetocin during the birthing process, with 34 sows experiencing natural farrowing and 66 sows receiving carbetocin. The sow's BCS was assessed through visual evaluation and palpation. The piglet colostrum consumption and the amount of colostrum produced by the sows were determined. The concentrations of IgG and IgA were determined by using the enzyme-linked immunosorbent assay (ELISA) technique. On average, the colostrum production averaged 5.5 ± 1.7 kg, with IgG and IgA concentrations averaging 54.9 ± 24.6 mg/ml and 7.6 ± 3.5 mg/ml, respectively. Primiparous sows exhibited a significant 25.2% decrease in IgG concentration within 6 h of parturition (P < 0.05), whereas no such decline was observed in multiparous sows. Furthermore, multiparous sows displayed higher colostrum yields (6.2 ± 1.5 kg and 4.3 ± 1.5 kg, respectively, P < 0.001) and IgA concentrations compared to primiparous sows (8.3 ± 3.8 mg/ml and 6.3 ± 2.6 mg/ml, respectively, P = 0.002). Furthermore, a positive correlation was observed between IgA concentrations in colostrum and the sow's BCS at both the 0-h and 6-h post-farrowing time points (r = 0.425, P = 0.002 and r = 0.315, P = 0.031, respectively). The administration of carbetocin did not yield a significant impact on the concentrations of IgG and IgA in the sows' colostrum (P > 0.05). In conclusion, during the initial 6 h after birth, colostrum IgA levels remained stable, whereas there was a noticeable decline in IgG levels, particularly among primiparous sows. The production volume of colostrum and the concentration of IgA in sows within tropical conditions were influenced by both parity number and body condition score.

Short communication: Temporal profiles of colostrum and milk haptoglobin and substance P in early lactation multiparous Holstein cows.

Milk markers have the potential to aid in the detection of cow disease in early lactation if the automation of milk analysis becomes commonplace. Characterising temporal profiles of milk markers in dairy cows will improve the understanding of basal concentrations in clinically healthy cows. The objective of this observational study was to characterise the variation and temporal profiles of colostrum and milk haptoglobin (Hp) and substance P concentrations within 21 days postcalving in clinically healthy multiparous Holstein dairy cows. Ninety Holstein dairy cows from a commercial dairy herd were included. Milk samples were collected on the day of calving (day 0), and on days 1 to 4, 7, 14, and 21 postcalving and concentrations of Hp and substance P in colostrum (days 0 to 3) and milk (days 4, 7, 14, and 21) were determined using Enzyme Linked Immunosorbent assay. Haptoglobin and substance P concentrations were, on average (raw means ± SD), 0.40 ± 0.26 µg/ml and 56.2 ± 38.7 pg/ml in colostrum, respectively, and 0.23 ± 0.23 µg/ml and 37.1 ± 27.8 pg/ml in milk, respectively. Haptoglobin and substance P were elevated and greatest 1 day postcalving (least squares mean ± SE of the mean; 0.53 ± 0.05 µg/ml and 46.5 ± 3.64 pg/ml, respectively) and substance P varied widely within 21 days postcalving. The presence of substance P in dairy cow colostrum was not documented previously. Elevated concentrations of Hp and substance P immediately postcalving may be due to physiological roles these inflammatory markers have in the dairy cow or neonate or may simply represent an accumulation in colostrum before the first milk is removed.

Effect of bovine colostrum liposomes on the bioavailability of immunoglobulin G and their immunoregulatory function in immunosuppressed BALB/c mice.

Bovine colostrum (BC) has high nutritional value; however, the low bioavailability of immune active substances in BC may affect their immunoregulatory function. Our previous studies indicated that encapsulating bovine colostrum with liposomes could enable the sustained release of immunoglobulin G in vitro; however, the effect of bovine colostrum liposomes (BCLs) on the bioavailability of immunoglobulins in vivo is still unknown. In addition, the immunoregulatory function of BCLs on immunosuppressed mice is still unclear. Therefore, our current study aimed to explore the effect of BCLs on the bioavailability of immunoglobulins, and further explore their immunoregulatory effect on immunosuppressed BALB/c mice. Through metabolic cage experiments, it was shown that BCLs decreased the urine and fecal concentrations of IgG and exhibited a higher bioavailability of IgG in mice than BC (about 2-fold). In addition, by establishing an immunosuppressed animal model, it was found that BCLs could increase the body weight, spleen weight, and thymus weight in immunosuppressed BALB/c mice, which further restored the serum levels of interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). Through histology analysis, it was suggested that BCLs restored the structure of jejunal epithelial cells, which was accompanied by an improvement in intestinal cytokine levels (IL-4, IL-10, TNF-α, and IFN-γ). Finally, BCLs increased serum and intestine concentrations of immunoglobulin G (IgG) and immunoglobulin A (IgA) in immunosuppressed BALB/c mice, which further indicated that BCLs had a sustained-release effect for immunoglobulin G in vivo. Our current research will provide a basis for understanding the role of BCLs on the bioavailability of IgG and their immunoregulatory effect on immunosuppressed mice, which might further provide some reference for the application of BCLs.

Testing detectability, attractivity, hedonic specificity, extractability, and robustness of colostrum odor-Toward an olfactory bioassay for human neonates.

Human milk odor is attractive and appetitive for human newborns. Here, we studied behavioral and heart-rate (HR) responses of 2-day-old neonates to the odor of human colostrum. To evaluate detection in two conditions of stimulus delivery, we first presented the odor of total colostrum against water. Second, the hedonic specificity of total colostrum odor was tested against vanilla odor. Third, we delivered only the fresh effluvium of colostrum separated from the colostrum matrix; the stability of this colostrum effluvium was then tested after deep congelation; finally, after sorptive extraction of fresh colostrum headspace, we assessed the activity of colostrum volatiles eluting from the gas chromatograph (GC). Regardless of the stimulus-delivery method, neonates displayed attraction reactions (HR decrease) as well as appetitive oral responses to the odor of total colostrum but not to vanilla odor. The effluvium separated from the fresh colostrum matrix remained appetitive but appeared labile under deep freezing. Finally, volatiles from fresh colostrum effluvium remained behaviorally active after GC elution, although at lower magnitude. In sum, fresh colostrum effluvium and its eluate elicited a consistent increase in newborns' oral activity (relative to water or vanilla), and they induced shallow HR decrease. Newborns' appetitive oral behavior was the most reproducible response criterion to the effluvium of colostrum. In conclusion, a set of unidentified volatile compounds from human colostrum is robust enough after extraction from the original matrix and chromatographic processing to continue eliciting appetitive responses in neonates, thus opening new directions to isolate and assay specific volatile molecules of colostrum.

Antirotaviral activity of dairy byproducts enriched in fractions from hyperimmune bovine colostrum: the effect of thermal and high hydrostatic pressure treatments.

Nowadays, rotaviruses remain a major health burden, especially in developing countries, and strategies complementary to vaccination are needed. In this view, dairy fractions have attracted great scientific interest, due to their high content of bioactive compounds. The objective of this study was to evaluate the antiviral activity of whey and buttermilk enriched in proteins from hyperimmune bovine colostrum (HBC) against rotavirus. The enriched fractions were spray-dried and subsequently tested for their neutralizing activity against the bovine rotavirus WC3 strain in vitro, using differentiated Caco-2/TC7 cells. The highest antirotaviral activity was observed when whey and buttermilk were enriched in purified immunoglobulin G (IgG), showing complete rotavirus neutralization at concentrations of 3 and 6 mg mL-1 for whey and buttermilk, respectively. Additionally, the use of a crude immunoglobulin fraction also gave satisfactory results. The inhibitory activities of all samples significantly decreased after the application of heat, except for the IgG-enriched buttermilk which showed a slight increase of activity following the application of short-time treatments (75 or 85 °C for 20 s). This sample also showed a significant increase of activity (13%) after the application of low-intensity high hydrostatic pressure treatment (400 MPa for 5 min). The maximum loss of bioactivity was observed at 600 MPa for 10 min (31 and 20% for whey- and buttermilk-based formulas, respectively). This study provides relevant information on the potential of whey, buttermilk, and HBC to be part of functional products as complementary strategies to combat rotavirus infections.

Novel Multitarget ACE Inhibitory Peptides from Bovine Colostrum Immunoglobulin G: Cellular Transport, Efficacy in Regulating Endothelial Dysfunction, and Network Pharmacology Studies.

In this study, we used traditional laboratory methods, bioinformatics, and cellular models to screen novel ACE inhibitory (ACEI) peptides with strong ACEI activity, moderate absorption rates, and multiple targets from bovine colostrum immunoglobulin G (IgG). The purified fraction of the compound proteinase hydrolysate of IgG showed good ACEI activity. After nano-UPLC-MS/MS identification and in silico analysis, eight peptides were synthesized and verified. Among them, SFYPDY, TSFYPDY, FSWF, WYQQVPGSGL, and GVHTFP were identified as ACEI peptides, as they exhibited strong ACEI activity (with IC50 values of 104.7, 80.0, 121.2, 39.8, and 86.3 µM, respectively). They displayed good stability in an in vitro simulated gastrointestinal digestion assay. In a Caco-2 monolayer model, SFYPDY, FSWF, and WYQQVPGSGL exhibited better absorption rates and lower IC50 values than the other peptides and were thereby identified as novel ACEI peptides. Subsequently, in a H2O2-induced endothelial dysfunction (ED) model based on HUVECs, SFYPDY, FSWF, and WYQQVPGSGL regulated ED by reducing apoptosis and ROS accumulation while upregulating NOS3 mRNA expression. Network pharmacology analysis and RT-qPCR confirmed that they regulated multiple targets. Overall, our results suggest that SFYPDY, FSWF, and WYQQVPGSGL can serve as novel multitarget ACEI peptides.

Therapeutics effects of bovine colostrum applications on gastrointestinal diseases: a systematic review.

BACKGROUND: Evidence on the effects of bovine colostrum (BC) supplementation on gastrointestinal (GI) diseases is conflicting. OBJECTIVES: This systematic review summarized the findings of clinical trials (CTs) on the effects of BC supplementation on GI diseases. METHODS: A systematic search was conducted in online databases, including PubMed, ISI Web of Science, and Scopus, until March 2021 and updated until December 2023. CTs investigated BC's effect on any measurable symptomatic change in terms of GI health as the primary outcome variable or as one of the outcomes in any population eligible for this systematic review. RESULTS: Out of 6881 records, 22 CTs (uncontrolled = 4, cross-over = 1, and parallel = 17) with 1427 patients were enrolled in the systematic review. Diarrhea, the most frequently evaluated symptom (20 interventional arms), was decreased in frequency with BC supplementation in 15 of these arms. However, most studies reported no change in its duration. BC supplementation consistently reduced stool frequency across all seven studies. Abdominal pain relief was noted in four interventional arms but showed no improvement in five others. Assessment of other GI symptoms was limited, yielding inconclusive results. CONCLUSIONS: There is limited evidence on the effects of BC on GI diseases, with mixed findings. More well-designed controlled clinical trials are required to explore its effects.