Microglia through MFG-E8 signaling decrease the density of degenerating neurons and protect the brain from the development of cortical infarction after stroke.

Neuronal loss is a hallmark of stroke and other neurodegenerative diseases, and as such, neuronal loss caused by microglia has been thought to be a contributing factor to disease progression. Here, we show that microglia indeed contribute significantly to neuronal loss in a mouse model of stroke, but this microglial-dependent process of neuronal clearance specifically targets stressed and degenerating neurons in the ischemic cortical region and not healthy non-ischemic neurons. Nonspecific stimulation of microglia decreased the density of neurons in the ischemic cortical region, whereas specific inhibition of MFG-E8 signaling, which is required for microglial phagocytosis of neurons, had the opposite effect. In both scenarios, the effects were microglia specific, as the same treatments had no effect in mice whose microglia were depleted prior to stroke. Finally, even though the inhibition of MFG-E8 signaling increased neuronal density in the ischemic brain region, it substantially exacerbated the development of cortical infarction. In conclusion, microglia through MFG-E8 signaling contribute to the loss of ischemic neurons and, in doing so, minimize the development of cortical infarction after stroke.

Goat Milk Allergy and a Potential Role for Goat Milk in Cow's Milk Allergy.

In many parts of the world, goat milk has been part of the human diet for millennia. Allergy to goat's milk, not associated with allergy to cow's milk, is a rare disorder, although some cases have been described. Goat milk proteins have substantial homology with cow's milk proteins and even show cross-reactivity; therefore, they are not advised as an alternative to cow's milk for infants with IgE-mediated cow's milk allergies. However, there are indications that, due to the composition of the goat milk proteins, goat milk proteins show lower allergenicity than cow's milk due to a lower αS1-casein content. For this reason, goat milk might be a better choice over cow's milk as a first source of protein when breastfeeding is not possible or after the breastfeeding period. Additionally, some studies show that goat milk could play a role in specific types of non-IgE-mediated cow milk allergy or even in the prevention of sensitization to cow's milk proteins. This review discusses a possible role of goat milk in non-IgE mediated allergy and the prevention or oral tolerance induction of milk allergy.

Age-specific composition of milk microbiota in Tibetan sheep and goats.

This study investigates the dynamic changes in milk nutritional composition and microbial communities in Tibetan sheep and goats during the first 56 days of lactation. Milk samples were systematically collected at five time points (D0, D7, D14, D28, D56) post-delivery. In Tibetan sheep, milk fat, protein, and casein contents were highest on D0, gradually decreased, and stabilized after D14, while lactose and galactose levels showed the opposite trend. Goat milk exhibited similar initial peaks, with significant changes particularly between D0, D7, D14, and D56. 16S rRNA gene sequencing revealed increasing microbial diversity in both species over the lactation period. Principal coordinates analysis identified distinct microbial clusters corresponding to early (D0-D7), transitional (D14-D28), and mature (D56) stages. Core phyla, including Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, dominated the milk microbiota, with significant temporal shifts. Core microbes like Lactobacillus, Leuconostoc, and Streptococcus were common in both species, with species-specific taxa observed (e.g., Pediococcus in sheep, Shewanella in goats). Furthermore, we observed a highly shared core microbiota in sheep and goat milk, including Lactobacillus, Leuconostoc, and Streptococcus. Spearman correlation analysis highlighted significant relationships between specific microbial genera and milk nutrients. For instance, Lactobacillus positively correlated with total solids, non-fat milk solids, protein, and casein, while Mannheimia negatively correlated with protein content. This study underscores the complex interplay between milk composition and microbial dynamics in Tibetan sheep and goats, informing strategies for livestock management and nutritional enhancement. KEY POINTS: • The milk can be classified into three types based on the microbiota composition • The changes of milk microbiota are closely related to the variations in nutrition • Filter out microbiota with species specificity and age specificity in the milk.

A retrospective comparison of IgE-mediated cow's milk protein allergy management strategies in pediatric cohorts.

BACKGROUND: Complete avoidance of milk is the usual management for IgE-mediated cow's milk protein allergy (CMPA). A baked milk ladder is a method of dietary advancement therapy in IgE-mediated CMPA in Ireland, while in Spain, avoidance of milk awaiting natural tolerance acquisition through an oral food challenge (OFC) is employed. The aim of this study was to evaluate the use of dietary advancement therapy using a milk ladder compared with complete avoidance of milk for managing IgE-mediated CMPA. METHODS: This is a retrospective chart review of 371 pediatric patients from the population who have been treated for IgE-mediated CMPA between 2011 and 2020, with the milk ladder (Ireland) or complete avoidance followed by an OFC (Spain). The main outcome was the introduction of cow's milk. RESULTS: Milk ladder patients were 3.67 times more likely to succeed in comparison with milk avoidance (p < .001). Anaphylaxis during the treatment period occurred in 34 patients in the milk avoidance groups, while three patients in the milk ladder group experienced anaphylaxis due to accidental exposure to milk (p < .001). Failure to complete treatment was associated with a higher skin prick test in the milk avoidance group and a raised specific IgE in the milk ladder group. CONCLUSION: This is the first study that compares outcomes of dietary advancement therapy to complete avoidance for CMPA management, demonstrating that cow's milk can be successfully and safely reintroduced using dietary advancement therapy using a milk ladder.

Risks of dairy derived excipients in medications for lactose intolerant and cow milk protein allergic patients.

The use of lactose and cow milk protein (CMP) as potential allergens in pharmaceuticals and their ability to cause allergic reactions remains a significant concern in medicine. Lactose, a common pharmaceutical excipient due to its inert, inexpensive, and stable properties, is found in many prescription-only and over-the-counter medications. However, despite their widespread use, individuals with lactose intolerance (LI) or cow milk protein allergy (CMPA) may experience adverse reactions to these excipients. This study investigated the prevalence of lactose and other dairy-derived ingredients in pharmaceuticals marketed in Portugal. Using the Summary of Product Characteristics (SmPC) from the INFOMED database, various medications, including analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), and antiasthmatics, were analyzed. Results showed a high prevalence of dairy-derived excipients, particularly in antiasthmatic drugs (62.6%) and NSAIDs (39%). Although CMP are not explicitly mentioned in SmPCs, the presence of lactose as an ingredient poses a risk of cross-contamination. The findings emphasize the need for healthcare professionals to be aware of potential allergens in medications and the importance of developing lactose-free alternatives to ensure the safety of patients with LI and CMPA. Further research is required to assess the safety and implications of lactose in medicines for these populations.

Milk Fat Globule-EGF Factor 8 (MFGE8) Mitigates Cognitive Impairment in Rats with Sepsis-Associated Encephalopathy: An fMRI Study.

BACKGROUND: Sepsis-associated encephalopathy (SAE) impairs hippocampal microglial efferocytosis, causing cognitive deficits. Previous research found that milk fat globule epidermal growth factor 8 protein (MFGE8) stimulates efferocytosis, reducing hippocampal inflammation in SAE rats. In this study, we explore MFGE8's role in alleviating cognitive impairment and its impact on neural activity using functional magnetic resonance imaging (fMRI). METHODS: Sixty male Sprague Dawley rats were divided into four groups: Sham, cecal ligation and puncture (CLP), CLP+MFGE8, and CLP+MFGE8+CGT (Cilengitide). After CLP, CLP+MFGE8 rats received intracerebroventricular MFGE8 (3.3 µg), while CLP+MFGE8+CGT rats received intraperitoneal Cilengitide (10 mg/kg). We assessed cognitive function with the Morris water maze and open field test over five days. Eight days post-surgery, rats underwent T2-weighted magnetic resonance imaging (MRI) and resting state (rs)-fMRI scans. Brain tissues were collected for western blot, hematoxylin-eosin (HE) staining, and immunofluorescence. Statistical analysis employed one-way analysis of variance (ANOVA) followed by Tukey's post-test for multiple comparisons. RESULTS: MFGE8 improved neurobehavioral performance in open field task (OFT) and morris water maze (MWM) tests. fMRI indicated a significant reduction in abnormal neural activity in the right hippocampal CA1, CA3, and dentate gyrus of SAE rats following MFGE8 treatment. Voxel-based morphometry (VBM) analysis revealed decreased high-signal areas in the hippocampus, along with reduced hippocampal volume due to alleviated neural edema. Western blot analysis demonstrated that MFGE8 enhanced ras-related C3 botulinum toxin substrate 1 (Rac1) and microtubule-associated protein 1A/1B-light chain 3 (LC3) expression in the rat hippocampus, while CGT reduced these protein levels. Behavioral experiments and fMRI results confirmed that CGT reversed the cognitive effects of MFGE8 by inhibiting microglial αVß3/αVß5 integrin receptors. CONCLUSIONS: Our findings show that MFGE8 reduced amplitude of low-frequency fluctuations (ALFF) values in the right hippocampal CA1, CA3, and the dentate gyrus, mitigating abnormal neural activity and decreasing hippocampal volume. This led to an improvement in cognitive dysfunction in SAE rats. These results suggest that MFGE8 enhances microglial efferocytosis by activating αVß3 and αVß5 integrin receptors on microglial surfaces, ultimately improving cognitive function in SAE rats.

Human Milk Protein-Derived Bioactive Peptides from In Vitro-Digested Colostrum Exert Antimicrobial Activities against Common Neonatal Pathogens.

Human milk reduces risk for necrotizing enterocolitis in preterm infants. Necrotizing enterocolitis occurs in the ileocecal region where thousands of milk protein-derived peptides have been released from digestion. Digestion-released peptides may exert bioactivity, such as antimicrobial and immunomodulatory activities, in the gut. In this study, we applied mass spectrometry-based peptidomics to characterize peptides present in colostrum before and after in vitro digestion. Sequence-based computational modeling was applied to predict peptides with antimicrobial activity. We identified more peptides in undigested samples, yet the abundances were much higher in the digested samples. Heatmapping demonstrated highly different peptide profiles between undigested and digested samples. Four peptides (αS1-casein [157-163], αS1-casein [157-165], ß-casein [153-159] and plasminogen [591-597]) were selected, synthesized and tested against common pathogenic bacteria associated with necrotizing enterocolitis. All four exhibited bacteriostatic, though not bactericidal, activities against Klebsiella aerogenes, Citrobacter freundii and Serratia marcescens, but not Escherichia coli.

Mammary fat globules as a source of mRNA to model alterations in the expression of some milk component genes during lactation in bovines.

BACKGROUND: The milk's nutritional value is determined by its constituents, including fat, protein, carbohydrates, and minerals. The mammary gland's ability to produce milk is controlled by a complex network of genes. Thereby, the fat, protein, and lactose synthesis must be boost in milk to increase milk production efficiency. This can be accomplished by fusing genetic advancements with proper management practices. Therefore, this study aimed to investigate the association between the Lipoprotein lipase (LPL), kappa casein CSN3, and Glucose transporter 1 (GLUT1) genes expression levels and such milk components as fat, protein, and lactose in different dairy breeds during different stages of lactation. METHODS: To achieve such a purpose, 94 milk samples were collected (72 samples from 36 multiparous black-white and red-white Holstein-Friesian (HF) cows and 22 milk samples from 11 Egyptian buffaloes) during the early and peak lactation stages. The milk samples were utilized for milk analysis and genes expressions analyses using non- invasive approach in obtaining milk fat globules (MFGs) as a source of Ribonucleic acid (RNA). RESULTS: LPL and CSN3 genes expressions levels were found to be significantly higher in Egyptian buffalo than Holstein-Friesian (HF) cows as well as fat and protein percentages. On the other hand, GLUT1 gene expression level was shown to be significantly higher during peak lactation than early lactation. Moreover, lactose % showed a significant difference in peak lactation phase compared to early lactation phase. Also, fat and protein percentages were significantly higher in early lactation period than peak lactation period but lactose% showed the opposite pattern of Egyptian buffalo. CONCLUSION: Total RNA can be successfully obtained from MFGs. The results suggest that these genes play a role in glucose absorption and lactose synthesis in bovine mammary epithelial cells during lactation. Also, these results provide light on the differential expression of these genes among distinct Holstein-Friesian cow breeds and Egyptian buffalo subspecies throughout various lactation phases.

Discrimination of overheated pasteurized milk using mass spectrometry-based proteomics.

Milk is one of the most widely consumed foods globally. To protect consumer interests, it is essential to establish an analytical method to detect the degree of heating in milk. A novel approach using nano liquid chromatography-orbitrap fusion mass spectrometer was developed for screening and identifing thermally sensitive peptides markers in the milk heating process (below 100 °C). This method integrates untargeted proteomics and chemometric tools to analyze protein quantitation data from differently heat-treated milk. Thirteen potential markers were screened out and identified, and further confirmed using by standard substances. Then, the accurate concentrations of 13 potential markers determined by isotope-dilution ultra-performance liquid chromatography-tandem triple quadrupole mass spectrometry were further mining the highly specific and thermally sensitive peptides markers. And Four peptides-INLFDTPLETQYVR, FELLGCELNGCTEPLGLK, QFQFIQVAGR, and GEADALNLDGGYIYTAGK-were selected as marker peptides to differentiate normal pasteurized milk from overheated pasteurized milk. The concentrations of INLFDTPLETQYVR ranges from 150 ± 11 µg/L to 350 ± 23 µg/L, while the concentrations of FELLGCELNGCTEPLGLK ranges from 40 ± 5 µg/L to 92 ± 3 µg/L, can distinguish normal pasteurized milk from overheated pasteurized milk. QFQFIQVAGR indicates overheated pasteurized milk at 230 ± 21 µg/L, and GEADALNLDGGYIYTAGK signifies 750 ± 43 µg/L. This study provides new insights for distinguishing overheated pasteurized milk.

Milk components as potential indicators of energy status in early lactation Holstein dairy cows from two farms.

Negative energy balance (NEB) is a serious problem in most dairy cows. It occurs most frequently after calving, when cows are unable to consume sufficient DM to meet their energy requirements during early lactation. During NEB, the breakdown of fat stores releases non-esterified fatty acids (NEFAs) into the bloodstream. High blood concentrations of NEFAs cause health problems such as ketosis, fatty liver syndrome, and enhanced susceptibility to infections. These issues may substantially increase premature culling from the herd. Serum NEFA concentrations are often used as a direct marker of energy metabolism. However, because the direct measurement of serum NEFAs is difficult under commercial conditions, alternative indicators, such as milk components, have been increasingly investigated for their use in estimating energy balance. The objectives of this study were to (1) evaluate the relationships between serum NEFA concentrations and selected milk components in cows from two farms during the first 5 weeks of lactation, and to (2) develop a model valid for both herds for predicting serum NEFA concentrations using milk components. A total of 121 lactating Holstein cows from two different farms were included in the experiment. Blood samples were collected for NEFA analysis on days 7 (± 3), 14 (± 3), 21 (± 3), and 35 (± 3) after calving. Composite milk samples were collected during afternoon milking on the same days as blood sampling. Concentrations of fat, protein, lactose, and milk fatty acids (FAs) were determined using Fourier-transform IR spectroscopy analysis. The strongest correlations (r > 0.43) were recorded between serum NEFAs and milk long-chain FAs, monounsaturated FAs, C18:0, and C18:1 within each farm and for both farms combined. Two prediction models for serum log(NEFA) using milk components as predictors were developed by stepwise regression. The prediction model with the best fit (R2 = 0.52) included days in milk, fat-to-protein ratio, and C18:1, C18:12 and C14:0 expressed as g/100 g of milk fat. An essential finding is that, despite different concentrations of NEFAs, and of most milk components observed in the evaluated herds, there were no significant interactions between farm and any of the FAs, so the same regression coefficients could be used for the prediction models in both farms. Validation of these findings in a greater number of herds would allow for the use of milk FAs to identify energy-imbalanced cows in herds under different farm conditions.

Developmental programming of production and reproduction in dairy cows: V. Association of the main and interactive effects of maternal level of milk production and milk fat to protein ratio with offspring's birth weight, survival, and productive and reproductive performance from birth to the first lactation period.

Level of dam milk production (DMP) and dam milk fat to protein ratio (DFPR), as an indicator of metabolic status in dairy cows, have been identified to be associated with productive and reproductive performance of the offspring. Yet whether the interaction of DMP by DFPR can be associated with performance of the offspring have not been studied to our knowledge. Therefore, the present study was conducted to investigate the association of the main and interactive effects of DMP and DFPR with offspring's birth weight, survival, milk yield and fertility. To this end, data of birth weight, culling rate, milk yield and reproductive variables of offspring born to lactating dams (n = 14,582) and data associated with DMP and DFPR during 305-day lactation were retrieved. Afterwards, offspring were classified in three categories of DMP, including DMP1 (dams with <10.00 × 103 kg of 305-day milk production), DMP2 (dams with ≥10.00 × 103 kg and <14.00 × 103 kg of 305-day milk production), DMP3 (dams with ≥14.00 × 103 kg of 305-day milk production), and three categories of DFPR, including DFPR1 (offspring born to dams with <1.00 FPR), DFPR2 (offspring born to dams with ≥1.00 and < 1.40 FPR) and DFPR3 (offspring born to dams with ≥1.40 FPR). Statistical analysis revealed no association of the interaction effect of DMP by DFPR with investigated variables in the offspring (P > 0.05). However, the main effect of DMP was positively associated with milk yield, but negatively associated with survival, age at first insemination and conception during nulliparity, and transgenerational improvement in milk yield in the offspring (P < 0.05). Moreover, the main effect of DFPR was positively associated with birth weight, survival and first service conception rate during nulliparity, but negatively associated with metabolic status and reproductive performance during primiparity in the offspring (P < 0.05). In conclusion, the present study did not find any interaction effect of DMP by DFPR on productive and reproductive variables in the offspring. This finding implicates the association of DMP with milk production in the offspring was regardless of DFPR. Moreover, this finding implies the association of DFPR with postpartum metabolic status and reproductive performance in the offspring was regardless of DMP.

Prior thermal and high-pressure processing alters the impact of high intensity ultrasound on reconstituted skim milk.

Reconstituted skim milk was subjected to heat treatment at 85 °C for 20 min or high pressure processing (HPP) at 400 or 600 MPa for 15 min with or without subsequent high intensity ultrasound (US) at 68 kHz, 500 W for 15 min at 30 °C. Untreated and treated samples were analyzed for particle size distribution, zeta potential, surface hydrophobicity, and concentration of total and surface sulfhydryl groups in addition to Native- and SDS-PAGE of serum phase upon ultracentrifugation and pH adjustment. Preceding heat- and HPP altered the impact of the subsequent US treatment, demonstrating process- and intensity-dependent exposure and burial of surface reactive sites on milk proteins respectively. US following HPP promoted sedimentation of HPP-dispersed serum casein fractions, while US following heat was directed mainly at the whey proteins originally bound to the micelles. The primary US effect on the untreated and treated milk proteins was at the molecular level.

Milk Fat Globule Membrane-Containing Protein Powder Promotes Fitness in Caenorhabditis elegans.

Milk-derived peptides and milk fat globule membrane (MFGM) have gained interest as health-promoting food ingredients. However, the mechanisms by which these nutraceuticals modulate the function of biological systems often remain unclear. We utilized Caenorhabditis elegans to elucidate how MFGM-containing protein powder (MProPow), previously used in a clinical trial, affect the physiology of this model organism. Our results demonstrate that MProPow does not affect lifespan but promotes the fitness of the animals. Surprisingly, gene expression analysis revealed that MProPow decreases the expression of genes functioning on innate immunity, which also translates into reduced survival on pathogenic bacteria. One of the innate immunity-associated genes showing reduced expression upon MProPow supplementation is cpr-3, the homolog of human cathepsin B. Interestingly, knockdown of cpr-3 enhances fitness, but not in MProPow-treated animals, suggesting that MProPow contributes to fitness by downregulating the expression of this gene. In summary, this research highlights the value of C. elegans in testing the biological activity of food supplements and nutraceuticals. Furthermore, this study should encourage investigations into whether milk-derived peptides and MFGM mediate their beneficial effects through the modulation of cathepsin B expression in humans.

Science and Faith to Understand Milk Bioactivity for Infants.

Milk bioactivity refers to the specific health effects of milk components beyond nutrition. The science of milk bioactivity involves the systematic study of these components and their health effects, as verified by empirical data, controlled experiments, and logical arguments. Conversely, 'faith in milk bioactivity' can be defined as personal opinion, meaning, value, trust, and hope for health effects that are beyond investigation by natural, social, or human sciences. Faith can be strictly secular, but also influenced by spirituality or religion. The aim of this paper is to show that scientific knowledge is frequently supplemented with faith convictions to establish personal and public understanding of milk bioactivity. Mammalian milk is an immensely complex fluid containing myriad proteins, carbohydrates, lipids, and micronutrients with multiple functions across species, genetics, ages, environments, and cultures. Human health includes not only physical health, but also social, mental, and spiritual health, requiring widely different fields of science to prove the relevance, safety, and efficacy of milk interventions. These complex relationships between milk feeding and health outcomes prevent firm conclusions based on science and logic alone. Current beliefs in and understanding of the value of breast milk, colostrum, infant formula, or isolated milk proteins (e.g., immunoglobulins, α-lactalbumin, lactoferrin, and growth factors) show that both science and faith contribute to understand, stimulate, or restrict the use of milk bioactivity. The benefits of breastfeeding for infants are beyond doubt, but the strong beliefs in its health effects rely not only on science, and mechanisms are unclear. Likewise, fear of, or trust in, infant formula may rely on both science and faith. Knowledge from science safeguards individuals and society against 'milk bioactivity superstition'. Conversely, wisdom from faith-based convictions may protect science from unrealistic 'milk bioactivity scientism'. Honesty and transparency about the potentials and limitations of both scientific knowledge and faith convictions are important when informing individuals and society about the nutritious and bioactive qualities of milk.

Influence of different milking methods on milk quality based on somatic cell count and basic composition.

INTRODUCTION AND OBJECTIVE: Correlations between the number of milk somatic cells (SCC), the number of microorganisms, and the content of basic components of milk were studied on five farms (F1-F5) with cows of the same breed, but with different milking systems. MATERIAL AND METHODS: From each farm, 50 Holstein Friesien milk samples were collected once a month (250 samples/month; n=3,000) during March 2022 - February 2023. Samples from farms F1 and F5 were tested for fat, protein, lactose, no fat dry matter content (FTIR spectroscopy), for the SCC (Fossomatic 7), and for the differential cells (Vetscan DC-Q). RESULTS: The highest fat content was confirmed on farm F5 (3.85 ± 1.70%) and F4 (3.82 ± 0.21%) with automatic milking system (AMS). However, from the point of view of protein content, these farms showed slightly lower values (<0.05). F1 did not meet the minimum required amount for fat content (2.84 ± 0.81%) set by the legislation of the Slovakia. The comparison shows that there is not much difference in cell size between healthy cells and mastitis cells. The average size of healthy cells was approximately 8.77 ± 0.49 µm. In the monitored period, the average values determined were at the level of 292,000/mL (5.46 ± 0.72 log10 SCC) in cow milk samples, while for the rest of the year, the values remained at 256,000/mL (5.40 ± 0.80 log10 SCC). F1 was categorized as a positive farm with a high TLC (total milk leucocyte count) concentration (5.58 log10 cells/mL, 406.65 ± 53.80 × 103 cells/mL) and a predominant NEU fraction (61%). Farms F2, F4, and F5 were classified as negative farms (TLC was 4.70 ± 0.26 log10 cells/ml). CONCLUSIONS: According to the results, the size of SCCs in healthy milk does not differ from SCCs found in mastitis milk. From the results, it can be concluded that the transition to the latest generation of robotic milking method can positively affect milk production and its quality.

Reference Material Production and Milk Protein Concentration as Elements to Improve Bluetongue Serological Diagnosis in Bulk Tank Milk.

The serological surveillance of bluetongue in bulk tank milk is an efficient and cost-effective method for the early detection of bluetongue virus incursions in unvaccinated free areas of the disease. In addition, the availability of standardized and reliable reagents and refined diagnostic procedures with high sensitivity and specificity are essential for surveillance purposes. However, no available reference materials for bluetongue virus serological surveillance in bulk tank milk exist. This study shows the production and characterization of reference material for the implementation of a commercially available bluetongue milk ELISA test in official laboratories, as well as the evaluation of a procedure to increase the sensitivity in samples with low levels of antibodies. This procedure, based on milk protein concentration, allowed us to notably increase the ELISA test's analytical sensitivity, which is useful for milk samples from farms with low within-herd prevalence or pools of bulk tank milk samples. The standardized milk reference material produced here, together with the evaluated procedure to improve analytical sensitivity, could be applied as tools to ensure an accurate diagnosis by official laboratories in bluetongue unvaccinated free areas.

Shift from Cow's Milk Food Protein-Induced Enterocolitis Syndrome to IgE-Mediated Allergy: Case Series and Literature Review.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by gastrointestinal symptom onset within 1-4 hours from trigger food ingestion. In the literature, some authors have previously described the possibility that a patient with FPIES may develop an IgE-mediated allergy to the same trigger food, especially cow's milk (CM). Case Presentation: We reported five cases of CM-FPIES converting to IgE-mediated CM allergy presented at our tertiary pediatric Allergy Unit and performed a review of the literature, aiming to characterize the clinical features of patients who are at risk of developing such conversion. Conclusions: This phenomenon raises the question of whether IgE-mediated and non-IgE-mediated allergies represent a spectrum of the same disease and highlights the need for further investigation to understand the pathophysiological mechanisms of this process.

Improved breast milk proteome coverage by DIA based LC-MS/MS method.

The breast milk composition includes a multitude of bioactive factors such as viable cells, lipids and proteins. Measuring the levels of specific proteins in breast milk plasma can be challenging because of the large dynamic range of protein concentrations and the presence of interfering substances. Therefore, most proteomic studies of breast milk have been able to identify under 1000 proteins. Optimised procedures and the latest separation technologies used in milk proteome research could lead to more precise knowledge of breast milk proteome. This study (n = 53) utilizes three different protein quantification methods, including direct DIA, library-based DIA method and a hybrid method combining direct DIA and library-based DIA. On average we identified 2400 proteins by hybrid method. By applying these methods, we quantified body mass index (BMI) associated variation in breast milk proteomes. There were 210 significantly different proteins when comparing the breast milk proteome of obese and overweight mothers. In addition, we analysed a small cohort (n = 5, randomly selected from 53 samples) by high field asymmetric waveform ion mobility spectrometry (FAIMS). FAIMS coupled with the Orbitrap Fusion Lumos mass spectrometer, which led to 41.7% higher number of protein identifications compared to Q Exactive HF mass spectrometer.

Milk serum peptidomics revealed the age gelation of direct UHT milk.

Age gelation is undesirable for direct UHT (dUHT) milk, which is closely related to protein hydrolysis. However, little information is available for the role of serum peptides during the age gelation. In this study, the composition and protein morphology of serum phase were characterized by RP-HPLC, ICP-MS and TEM. The results showed significant increases in soluble proteins, free amino acids, calcium, and phosphorus from casein micelles, indicating protein hydrolysis and peptide release into the serum phase. 23,466 peptides derived from caseins and other proteins were identified in serum phase by peptidomics. The serum peptide profiles of age gelation milk changed dramatically. Peptide fingerprinting revealed that plasmin and cathepsin contributed to the protein hydrolysis during age gelation, with a significant increase in their activity observed. 23 characteristic peptides were ultimately selected as potential indicators for age gelation. These findings provide new insights into the age gelation of UHT milk.

Effects of high-quality protein supplementation on cardiovascular risk factors in individuals with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Uncertainties still existed about the effect of high-quality protein supplementation on cardiovascular disease (CVD) risk factors, although high-quality proteins such as soy and milk proteins have proposed to be beneficial for cardiometabolic health. METHODS: A systematic search in PubMed, Web of Science, Cochrane Library, Scopus, and Embase was conducted to quantify the impact of high-quality protein on CVD risk factors. RESULTS: 63 RCTs on 4 types of high-quality protein including soy protein, milk protein, whey, and casein were evaluated. Soy protein supplementation decreased systolic blood pressure (SBP, -1.42 [-2.68, -0.17] mmHg), total cholesterol (TC, -0.18 [-0.30, -0.07] mmol/L), and low-density lipoprotein cholesterol (LDL-C, -0.16 [-0.27, -0.05] mmol/L). Milk protein supplementation decreased SBP (-2.30 [-3.45, -1.15] mmHg) and total cholesterol (-0.27 [-0.51, -0.03] mmol/L). Whey supplementation decreased SBP (-2.20 [-3.89, -0.51] mmHg), diastolic blood pressure (DBP, -1.07 [-1.98, -0.16] mmHg), triglycerides (-0.10 [-0.17, -0.03] mmol/L), TC (-0.18 [-0.35, -0.01] mmol/L), LDL-C (-0.09 [-0.16, -0.01] mmol/L) and fasting blood insulin (FBI, -2.02 [-3.75, -0.29] pmol/L). Casein supplementation decreased SBP (-4.10 [-8.05, -0.14] mmHg). In the pooled analysis of four high-quality proteins, differential effects were seen in individuals with different health status. In hypertensive individuals, high-quality proteins decreased both SBP (-2.69 [-3.50, -1.87] mmHg) and DBP (-1.34 [-2.09, -0.60] mmHg). In overweight/obese individuals, high-quality proteins improved SBP (-1.40 [-2.22, -0.59] mmHg), DBP (-2.59 [-3.20, -1.98] mmHg), triglycerides (-0.09 [-0.15, -0.02] mmol/L), TC (-0.14 [-0.22, -0.05] mmol/L), LDL-C (-0.12 [-0.16, -0.07] mmol/L), and HDL-C levels (0.02 [0.01, 0.04] mmol/L). According to the benefits on CVD risks factors, whey ranked top for improving cardiometabolic health in hypertensive or overweight/obese individuals. CONCLUSION: Our study supports a beneficial role of high-quality protein supplementation to reduce CVD risk factors. Further studies are still warranted to investigate the effects of different high-quality proteins on CVD risks in individuals with cardiometabolic disorders.