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The accurate estimation of basal endogenous losses (BEL) of amino acids at the ileum is indispensable to improve nutrient utilization efficiency. This study used a quantitative proteomic approach to identify variations in BEL in the ileal digesta of growing pigs fed a nitrogen-free diet (NFD) or a casein diet (CAS). Eight barrow pigs (39.8 ± 6.3 kg initial body weight (BW)) were randomly assigned to a 2 × 2 crossover design. A total of 348 proteins were identified and quantified in both treatments, of which 101 showed a significant differential abundance between the treatments (p < 0.05). Functional and pathway enrichment analyses revealed that the endogenous proteins were associated with intestinal metabolic function. Furthermore, differentially abundant proteins (DAPs) in the digesta of pigs fed the NFD enriched terms and pathways that suggest intestinal inflammation, the activation of innate antimicrobial host defense, an increase in cellular autophagy and epithelial turnover, and reduced synthesis of pancreatic and intestinal secretions. These findings suggest that casein diets may provide a more accurate estimation of BEL because they promote normal gastrointestinal secretions. Overall, proteomic and bioinformatic analyses provided valuable insights into the composition of endogenous proteins in the ileal digesta and their relationship with the functions, processes, and pathways modified by diet composition.

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Cancer is one of the leading causes of death worldwide, with over 10 million fatalities annually. While tumors can be surgically removed and treated with chemotherapy, radiotherapy, immunotherapy, hormonal therapy, or combined therapies, current treatments often result in toxic side effects in normal tissue. Therefore, researchers are actively seeking ways to selectively eliminate cancerous cells, minimizing the toxic side effects in normal tissue. Caseins and its derivatives have shown promising anti-cancer potential, demonstrating antitumor and cytotoxic effects on cells from various tumor types without causing harm to normal cells. Collectively, these data reveals advancements in the study of caseins and their derivative peptides, particularly providing a comprehensive understanding of the molecular mechanism of action in cancer therapy. These mechanisms occur through various signaling pathways, including (i) the increase of interferon-associated STAT1 signaling, (ii) the suppression of stemness-related markers such as CD44, (iii) the attenuation of the STAT3/HIF1-α signaling, (iv) the down-expression of uPAR and PAI-1, (v) the loss of mitochondrial membrane potential and reduced intracellular ATP production, (vi) the increase of caspase-3 activity, and (vii) the suppression of TLR4/NF-кB signaling. Therefore, we conclude that casein could be an effective adjuvant for cancer treatment.

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Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 (Belumosudil) is a newly developed inhibitor that selectively targets ROCK2. It has exhibited consistent efficacy in impeding adipogenesis across a spectrum of in vitro models of adipogenic differentiation. Given the novelty of this treatment, a comprehensive systematic review has not been conducted yet. This systematic review aims to fill this knowledge void by providing readers with an extensive examination of the rationale behind KD025 and its impacts on adipogenesis. Preclinical evidence was gathered owing to the absence of clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study's quality was assessed using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews. In various in vitro models, such as 3T3-L1 cells, human orbital fibroblasts, and human adipose-derived stem cells, KD025 demonstrated potent anti-adipogenic actions. At a molecular level, KD025 had significant effects, including decreasing fibronectin (Fn) expression, inhibiting ROCK2 and CK2 activity, suppressing lipid droplet formation, and reducing the expression of proadipogenic genes peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Additionally, KD025 resulted in the suppression of fatty acid-binding protein 4 (FABP4 or AP2) expression, a decrease in sterol regulatory element binding protein 1c (SREBP-1c) and Glut-4 expression. Emphasis must be placed on the fact that while KD025 shows potential in preclinical studies and experimental models, extensive research is crucial to assess its efficacy, safety, and potential therapeutic applications thoroughly and directly in human subjects.

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Research background: A few studies have investigated Cynara scolymus enzymes as a substitute for calf rennet in cheese making. They used aqueous extracts prepared by maceration of plant material and stored by freezing. However, it was indicated that lyophilisation is a better alternative to preserve the coagulant properties of plant extracts over a longer period of time, as it is a more controllable, stable and hygienic alternative with a better shelf life that is easier to transport, store and standardise. Experimental approach: We obtained a lyophilised extract of mature artichoke flowers, named CS, which was characterised for its milk-clotting properties at different pH and temperatures. In addition, the potential yield, whey composition and the primary hydrolysis profile of caseins by urea-polyacrylamide gel electrophoresis (PAGE) of mini curds prepared with different doses of coagulant were determined. Results and conclusions: The lyophilised extract was able to hydrolyse casein and showed stable proteolytic activity at pH=6.4 and 37 °C for 50 min, which decreased when the process temperature was increased to 41 and 45 °C and was lost at 70 °C. On the other hand, milk-clotting activity increased significantly (p<0.001) when the temperature increased from 37 to 45 °C and the pH of the milk decreased from 6.8 to 5.8. Potential yield ​​between 10 and 17 % was obtained for the mini curds prepared with the lyophilised artichoke extract, and the casein degradation pattern obtained by urea-PAGE was similar to that of the commercial coagulant. Novelty and scientific contribution: On a laboratory scale, our work has shown that the lyophilised artichoke extract has sufficient proteolytic and coagulant activity to be used as a milk coagulant, i.e. plant rennet, in cheese making as an alternative to animal rennet. As this extract is lyophilised, it has the advantage of being a better alternative in terms of preservation and shelf-life. It offers an innovative way to diversify cheese products and appeal to consumers with different dietary preferences and needs.

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The possible adverse effect of consuming bovine milk with A1 ß-casein (but not with A2 ß-casein) on health aspects due to the release of ß-casomorphin-7 (BCM-7) is currently under debate. The aim of this study was to perform a bibliometric analysis of studies extracted from Scopus to explore the relationship between BCM-7, A1 or A2 bovine milk with different aspects of health. Over time, several research groups were formed that are no longer active and although some authors have returned to the field of study, they have focused their efforts mainly on conducting reviews that show the same imprecise conclusions due to the few original articles. Research is concentrated in Europe and Asia, where New Zealand, China and Germany are the countries with the most publications, records and citations on the subject, respectively. On the other hand, no country in Africa or South America has scientific production, which opens the possibility of building collaborations between countries and exploring areas that lack scientific studies. Based on conflicting information from primarily in vitro and animal studies, and limited clinical trials with poor designs, A1 milk presents pro-inflammatory and oxidative activity, but the evidence is insufficient to associate its consumption with negative health effects. However, A2 milk may be better tolerated by the digestive system of some individuals, suggesting its possible modulating role in the intestinal microbiota. Stronger scientific evidence is needed to reach a consensus on whether the presence of ß-casein A1 can significantly negatively affect health. The information shown will allow a better understanding of the subject and consumers will be able to make their own decisions regarding A1 or A2 milk.

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ß-Casomorphin-7 (BCM-7) is a peptide released through the proteolysis of ß-casein (ß-CN), which is considered a bioactive peptide displaying evidence of promoting the binding and activation of the µ-opioid receptor located in various body parts, such as the gastrointestinal tract, the immune system and potentially the central nervous system. The possible effects of BCM-7 on health are a theme rising in popularity due to evidence found in several studies on the modulation of gastrointestinal proinflammatory responses that can trigger digestive symptoms, such as abdominal discomfort. With the advancement of studies, the hypothesis that there is a correlation of the possible effects of BCM-7 with the microbiota-gut-brain axis has been established. However, some studies have suggested the possibility that these adverse effects are restricted to a portion of the population, and the topic is controversial due to the small number of in vivo studies, which makes it difficult to obtain more conclusive results. In addition, a threshold of exposure to BCM-7 has not yet been established to clarify the potential of this peptide to trigger physiological responses at gastrointestinal and systemic levels. The proportion of the population that can be considered more susceptible to the effects of BCM-7 are evidenced in the literature review. The challenges of establishing the adverse effects of BCM-7 are discussed, including the importance of quantifying the BCM-7 release in the different ß-CN genotypes. In summary, the reviewed literature provides plausible indications of the hypothesis of a relationship between ß-CN A1/BCM-7 and adverse health effects; however, there is need for further, especially in vivo studies, to better understand and confirm the physiological effects of this peptide.

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Background: Gut microbiota plays a potential role in human health and different disorders such as autism spectrum disorder (ASD). Therefore, we analyzed gut bacteria composition in children with ASD and typical development (TD), and its relationship with nutritional status and dietary intake. Methods: A descriptive cross-sectional study was carried out in 3- to 12-year-old children (ASD = 30, TD = 28). Dietary intake (applying food frequency questionnaires) and body mass index-for-age (expressed in z-score) were determined. Children were divided into normal weight and excess weight (risk of overweight + overweight + obesity), and the ASD group was categorized into gluten- and casein-free diet (ASD-diet) or no diet (ASD-no diet). The relative abundance of gut bacteria was analyzed in fecal samples by 16S rRNA sequencing. Results: Children with excess weight had lower Roseburia than normal weight. Fewer Bifidobacterium longum and higher Clostridium glycolicum were found in the ASD group compared with TD one. Participants with excess weight and ASD had lower Roseburia and Faecalibacterium prausnitzii and higher Eubacterium ventricosum and Flavonifractor plautii than the TD group with the same nutritional status. Positive and negative associations were found between the bacteria genus and species, and the intake of dairy, vegetable drinks, cereals with and without gluten, food source of proteins, fish, food source of fat, and coconut oil, in unadjusted models and after adjustment for age, diet/no diet, ASD/TD. Conclusion: Significant differences in microbial community composition were found between children with ASD and TD, considering their nutritional status and dietary intake.

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A growing interest in the production and commercialization of A2 cow's milk has been observed in many countries in the last few years due to the beneficial properties for human health attributed to A2 ß-casein variant. Methods of varying complexity and different equipment requirements have been proposed for the determination of the ß-casein genotype of individual cows. We proposed herein a modification of a previously patented method based on an amplification-created restriction site PCR followed by restriction fragment length polymorphism analysis. This method allows to identify and differentiate A2-like from A1-like ß-casein variants, after differential endonuclease cleavage flanking the nucleotide that determines the amino acid at position 67 of ß-casein. The advantages of this method are that it: • enables to unequivocally score A2-like as well as A1-like ß-casein variants, • can be performed at low cost in simply equipped molecular biology laboratories, and • can be scaled up to analyze hundreds of samples per day. For these reasons, and based on the results obtained from the analysis carried out in this work, it showed to be a reliable method for the screening of herds to selective breeding of homozygous cows and bulls for A2 or A2-like alleles.

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Caseins are the main proteins in milk, and their structure and spatial conformation are responsible for their slow digestion rate. The release of bioactive and ß-casomorphin peptides from casein digestion may induce allergic responses during consumption. Spectroscopic techniques were used to observe the structural changes in casein conformation induced by Ultraviolet light irradiation (UV-C). Raman spectroscopy results showed more pronounced peaks at 618 and 640 cm-1 for phenylalanine and tyrosine moieties of the photolyzed micellar casein, respectively, suggesting changes in the micelle structure. The decrease in the intensity of Raman signals for tryptophan and tyrosine corroborates to the UV-C-induced modifications of the micelle structure. Particle size distribution showed a decrease in the average micelle size after 15 min of UV-C exposure, while low-temperature, long-time (LTLT) pasteurization led to the formation of large aggregates, as observed by atomic force microscopy. UV-C did not impact the formation or transport of peptides, as observed by using the Caco-2 cell as a model for peptide absorption. However, the absence of the opioid peptide SRYPSY from κ-casein and only 20% of the concentration of opioid peptide RYLGY were noted. This work demonstrated that UV-C can be utilized to induce the physicochemical modification of dairy products, promoting a higher digestion rate and reducing allergenicity.

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Casein is one of the most studied proteins with activity against dental caries. In particular, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) has shown promising remineralizing properties. In vivo evidence on the anticaries potential of CPP-ACP added to foodstuffs is elusive, nonetheless. Hence, this systematic review aimed at determining whether the use of CPP-ACP added to foodstuffs has a remineralizing or inhibitory action on dental demineralization either in vivo or in situ. The review protocol followed the PRISMA-P criteria and was registered in PROSPERO. PubMed, Scopus, and Web of Science databases were searched using predefined criteria, based on the PICO question: Is there an effect on dental caries upon adding CPP-ACP to milk, chewing gums, or candies? No year or language limits were applied. Article selection and data extraction were carried out independently by 2 investigators. Two hundred ten titles were examined, 23 were selected for full-text review, and 16 studies were included (2 in vivo and 14 in situ). CPP-ACP was added to candy in 2 studies, to milk in 2 studies, and to chewing gum in 12 studies. The main outcomes included enamel remineralization and activity against dental biofilm. The overall quality of the evidence was classified as moderate. The available evidence suggests that CPP-ACP added to milk, chewing gum, or candy has a potential remineralizing activity on tooth enamel, with some additional antibacterial activity on the dental biofilm. Further clinical studies are needed to verify if this effect is clinically significant in reducing the caries lesion incidence or to revert the demineralizing process.

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