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Food Research International (Ottawa,... Jul 2023The development of food-derived Xanthine Oxidase (XO) inhibitors is critical to the treatment of hyperuricemia and oxidative stress-related disease. Few studies report...
The development of food-derived Xanthine Oxidase (XO) inhibitors is critical to the treatment of hyperuricemia and oxidative stress-related disease. Few studies report on milk protein hydrolysates' XO inhibitory activity, with the mechanism of their interaction remaining elusive. Here, different commercial enzymes were used to hydrolyze α-lactalbumin and bovine colostrum casein. The two proteins hydrolyzed by alkaline protease exhibited the most potent XO inhibitory activity (bovine casein: IC = 0.13 mg mL; α-lactalbumin: IC = 0.28 mg mL). Eight potential XO inhibitory peptides including VYPFPGPI, GPVRGPFPIIV, VYPFPGPIPN, VYPFPGPIHN, QLKRFSFRSFIWR, LVYPFPGPIHN, AVFPSIVGR, and GFININSLR (IC of 4.67-8.02 mM) were purified and identified from alkaline protease hydrolysates by using gel filtration, LC-MS/MS and PeptideRanker. The most important role of inhibiting activity of peptides is linked to hydrophobic interactions and hydrogen bonding based on the results of molecular docking and molecular dynamics simulation. The enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein could be a competitive candidates for hyperuricemia-resisting functional food.
Topics: Animals; Cattle; Female; Pregnancy; Lactalbumin; Xanthine Oxidase; Caseins; Chromatography, Liquid; Colostrum; Molecular Docking Simulation; Hyperuricemia; Tandem Mass Spectrometry; Peptides; Enzyme Inhibitors
PubMed: 37254330
DOI: 10.1016/j.foodres.2023.112882 -
International Journal of Biological... Jul 2023The increasing global population and protein demand cause global challenges for food supply. Fueled by significant developments in synthetic biology, microbial cell... (Review)
Review
The increasing global population and protein demand cause global challenges for food supply. Fueled by significant developments in synthetic biology, microbial cell factories are constructed for the bioproduction of milk proteins, providing a promising approach for scalable and cost-effective production of alternative proteins. This review focused on the synthetic biology-based microbial cell factory construction for milk protein bioproduction. The composition, content, and functions of major milk proteins were first summarized, especially for caseins, α-lactalbumin, and β-lactoglobulin. An economic analysis was performed to determine whether cell factory-based milk protein production is economically viable for industrial production. Cell factory-based milk protein production is proved to be economically viable for industrial production. However, there still exist some challenges for cell factory-based milk protein biomanufacturing and application, including the inefficient production of milk proteins, insufficient investigation of protein functional property, and insufficient food safety evaluation. Constructing new high-efficiency genetic regulatory elements and genome editing tools, coexpression/overexpression of chaperone genes, and engineering protein secretion pathways and establishing a cost-effective protein purification method are possible ways to improve the production efficiency. Milk protein biomanufacturing is one of the promising approaches to acquiring alternative proteins in the future, which is of great importance for supporting cellular agriculture.
Topics: Milk Proteins; Gene Editing; Caseins; Protein Engineering; Lactalbumin; Metabolic Engineering
PubMed: 37315667
DOI: 10.1016/j.ijbiomac.2023.125335 -
Journal of Biomolecular Structure &... Aug 2023Colorectal cancer (CRC) is a malignant tumor recognized as a major cause of morbidity and mortality throughout the world. Therefore, novel liposomes of oleic acid coated...
Colorectal cancer (CRC) is a malignant tumor recognized as a major cause of morbidity and mortality throughout the world. Therefore, novel liposomes of oleic acid coated with camel α-lactalbumin (α-LA coated liposomes) were developed for their potential antitumor activity against CRC, both and in DMH-induced CRC-modeled animal. results indicated the high safety of α-LA coated liposomes towards normal human cells with potent antitumor activity against Caco-2 cells at an IC value of 57.01 ± 3.55 µM with selectivity index of 6.92 ± 0.48. This antitumor activity has been attributed to induction of the apoptotic mechanism, as demonstrated by nuclear condensation and arrest of Caco-2 cells in sub-G1 populations. α-LA coated liposomes also revealed a significant up-regulation of the p53 gene combined with a down-regulation of the Bcl2 gene. Moreover, results revealed that treatment of induced-CRC modeled animals with α-LA coated liposomes for six weeks markedly improved the CRC-disorders; this was achieved from the significant reduction in the values of AFP, CEA, CA19.9, TNF-α, IL-1β, MDA, and NO coupled with remarkable rise in SOD, GPx, GSH, CAT, and CD4+ levels. The histopathological findings asserted the therapeutic potential of α-LA coated liposomes in the treatment of CRC. Therefore, the present results proved the antitumor activity of α-LA coated liposomes against CRC through the restoration of impaired oxidative stress, improved immune response, and reduced inflammation.Communicated by Ramaswamy H. Sarma.
PubMed: 37624964
DOI: 10.1080/07391102.2023.2250452 -
Journal of Agricultural and Food... Apr 2024The gut barrier plays an important role in health maintenance by preventing the invasion of dietary pathogens and toxins. Disruption of the gut barrier can cause severe... (Review)
Review
The gut barrier plays an important role in health maintenance by preventing the invasion of dietary pathogens and toxins. Disruption of the gut barrier can cause severe intestinal inflammation. As a natural source, milk is enriched with many active constituents that contribute to numerous beneficial functions, including immune regulation. These components collectively serve as a shield for the gut barrier, protecting against various threats such as biological, chemical, mechanical, and immunological threats. This comprehensive review delves into the active ingredients in milk, encompassing casein, α-lactalbumin, β-lactoglobulin, lactoferrin, the milk fat globular membrane, lactose, transforming growth factor, and glycopeptides. The primary focus is to elucidate their impact on the integrity and function of the gut barrier. Furthermore, the implications of different processing methods of dairy products on the gut barrier protection are discussed. In conclusion, this study aimed to underscore the vital role of milk and dairy products in sustaining gut barrier health, potentially contributing to broader perspectives in nutritional sciences and public health.
Topics: Animals; Milk; Caseins; Lactalbumin; Lactoglobulins; Diet
PubMed: 38588092
DOI: 10.1021/acs.jafc.3c06861 -
Journal of Chemical Information and... Sep 2023A molten globule (MG) state is an intermediate state of protein observed during the unfolding of the native structure. In MG states, milk protein α-lactalbumin (aLA)...
A molten globule (MG) state is an intermediate state of protein observed during the unfolding of the native structure. In MG states, milk protein α-lactalbumin (aLA) binds to oleic acid (OLA). This MG-aLA-OLA complex, popularly known as XAMLET, performs cytotoxic activities against cancer cell lines. However, the microscopic understanding of ligand recognition ability in the MG state of the protein has not yet been explored. Motivated by this, we explore the binding of bovine aLA with OLA using all-atom molecular dynamics (MD) simulations. We find the binding mode between MG-aLA and OLA using the conformational thermodynamics method. We also estimate the binding free energy using the umbrella sampling (US) method for both the MG state and the neutral state. We find that the binding free energy obtained from US is comparable with earlier experimental results. We characterize the dihedral fluctuations as the ligand is liberated from the active site of the protein using steered MD. The low energy fluctuations occur near the ligand binding site, which eventually transfer toward the Ca-binding site as the ligand is taken away from the protein.
Topics: Animals; Cattle; Ligands; Binding Sites; Transcription Factors; Cell Line; Molecular Dynamics Simulation
PubMed: 37646788
DOI: 10.1021/acs.jcim.3c00642 -
Food and Chemical Toxicology : An... Aug 2023Cow's milk proteins allergy (CMA) is an atypical immune system response to cow's milk and dairy products. It's one of the most common food allergies in children... (Review)
Review
Cow's milk proteins allergy (CMA) is an atypical immune system response to cow's milk and dairy products. It's one of the most common food allergies in children affecting 8% of the total pediatric population pediatric population. This comprehensive review examines recent studies in CMA, especially regarding mammalian milk allergies such as goat's, sheep's, buffalo's, camel's, mare's and donkey's milk allergies in order to increase awareness of these selective allergies and to reduce allergy risks for those who have them. The consumption of other mammalian milk types is not recommended because of the significant homology between milk proteins from cow, sheep, goat and buffalo resulting in clinical cross-reactivity. However, camel's, mare's or donkey's milk may be tolerated by some allergic patients. Selective mammalian milk allergies are unusual and rare disorders characterized by severe symptoms including angio-oedema, urticaria, respiratory manifestations and anaphylaxis. Based on the reported allergic cases, cheese products including Ricotta, Romano, Pecorino and Mozzarella, are considered as the most common source of allergens especially in goat's, sheep's and buffalo's milk allergies, while the major allergens in donkey's and mare's milk seems to be whey proteins including lysozyme, α-lactalbumin and β-lactogloblin due to the low casein/whey proteins ratio in equine's milk.
Topics: Horses; Child; Animals; Humans; Female; Cattle; Sheep; Milk Proteins; Milk Hypersensitivity; Whey Proteins; Buffaloes; Camelus; Skin Tests; Allergens; Goats; Equidae
PubMed: 37406758
DOI: 10.1016/j.fct.2023.113929 -
Unlocking the potential of milk whey protein components in colorectal cancer prevention and therapy.Critical Reviews in Food Science and... Oct 2023Extensive research from large prospective cohort studies and meta-analytical investigations over recent decades have consistently indicated that dairy foods have... (Review)
Review
Extensive research from large prospective cohort studies and meta-analytical investigations over recent decades have consistently indicated that dairy foods have protective effects, reducing the risk of colorectal cancer. Most of the literature has explored the potential role of milk minerals and vitamins in managing colorectal cancer. Yet, there is a paucity of a comprehensive summary of the anticancer attributes of milk protein components and their underlying mechanisms of action. Recent advancements have spotlighted the potential of whey proteins, including β-lactoglobulin, α-lactalbumin, serum albumin, and lactoferrin, as promising candidates for both the prevention and treatment of colorectal cancer. Notably, whey proteins have demonstrated a more pronounced capacity for suppressing carcinogen-induced tumors when compared to casein. Their strong binding affinity enables them to serve as effective carriers for small molecules or drugs targeting colon cancer therapy. Furthermore, numerous studies have underscored the anti-inflammatory and antioxidant prowess of whey proteins in cancer prevention. Additionally, whey proteins have been shown to trigger apoptosis, hinder tumor cell proliferation, and impede metastasis. This comprehensive review, therefore, not only substantiates the significance of incorporating whey protein components into a balanced daily diet but also underscores their potential in safeguarding against the onset and progression of colorectal cancer.
PubMed: 37846905
DOI: 10.1080/10408398.2023.2258970 -
Pediatric Allergy, Immunology, and... Sep 2023Cases of cow's milk allergy (CMA) who reacted to measles or measles, mumps, and rubella (MMR) vaccines containing alpha-lactalbumin have been reported. The purpose of...
Cases of cow's milk allergy (CMA) who reacted to measles or measles, mumps, and rubella (MMR) vaccines containing alpha-lactalbumin have been reported. The purpose of this study was to assess patients with CMA who received measles or MMR vaccines containing alpha-lactalbumin, as well as the characteristics of those who developed reactions to these vaccines. Patients followed up in the allergy clinic for CMA and who received measles or MMR vaccines containing alpha-lactalbumin at 9 or 12 months of age were included in the study, and their characteristics were analyzed retrospectively from the hospital registry system. Forty-nine patients were included in the study. Six patients received the measles vaccine, whereas 43 patients received the MMR vaccine containing alpha-lactalbumin. Vaccine skin tests were performed on these 6 patients. One patient had a positive intradermal test, so an alternative vaccine not containing alpha-lactalbumin was administered. The other 5 patients were vaccinated, and no reaction was observed. Anaphylaxis was observed in 3 of 43 patients who received the MMR vaccine containing alpha-lactalbumin. In all of these patients, the first reaction to dairy products was anaphylaxis. In 2 of those patients, cow's milk-specific IgE (spIgE) levels were >100 kU/L, and alpha-lactalbumin-spIgE levels were also high at 97 and 90 kU/L. The third patient's cow's milk-spIgE level was 15.9 kU/L, whereas the alpha-lactalbumin-spIgE level was 0.04 kU/L. Especially in patients with an initial reaction of anaphylaxis to dairy products and high cow's milk-spIgE levels, the risk of reaction is high with the MMR vaccine.
Topics: Animals; Cattle; Female; Anaphylaxis; Immunoglobulin E; Lactalbumin; Measles-Mumps-Rubella Vaccine; Milk Hypersensitivity; Retrospective Studies; Humans; Milk
PubMed: 37433203
DOI: 10.1089/ped.2023.0035 -
International Journal of Biological... Jan 2024Amyloid fibrils are self-assembled aggregates of proteins and peptides that can lead to a broad range of diseases called amyloidosis. So far, no definitive and approved...
Amyloid fibrils are self-assembled aggregates of proteins and peptides that can lead to a broad range of diseases called amyloidosis. So far, no definitive and approved treatment to target directly amyloid fibrils has been introduced. Nevertheless, the search for small molecules with ability to inhibit and suppress fibril formation is an active and promising area of the research. Herein, the binding interactions and inhibitory effects of myricetin and morin hydrate on the in vitro fibrillation of bovine α-lactalbumin (BLA) have been investigated. The intrinsic fluorescence of BLA was quenched by myricetin and morin hydrate through combination of the static and dynamic quenching along with non-radiative Förster energy transfer mechanisms. The binding of these two flavonoids to BLA were not accompanied by major alteration in the conformation of BLA as evidenced by CD studies. The results of the fluorescence quenching analyses indicated almost the same binding affinities of myricetin and morin hydrate toward BLA (K ~ 10 M). However, the results of thioflavin T (ThT) assays showed that myricetin is a stronger inhibitor against BLA fibrillation compared to morin hydrate.
Topics: Animals; Cattle; Amyloid; Lactalbumin; Flavonoids
PubMed: 37939780
DOI: 10.1016/j.ijbiomac.2023.127908 -
Food Chemistry May 2024In this research, interactions between α-lactalbumin (ALA) and three protopanaxadiol ginsenosides [20(S)-Rg3, 20(S)-Rh2, and 20(S)-PPD] were compared to explore the...
In this research, interactions between α-lactalbumin (ALA) and three protopanaxadiol ginsenosides [20(S)-Rg3, 20(S)-Rh2, and 20(S)-PPD] were compared to explore the effects of similar ligand on structure and cytotoxicity of ALA. Multi-spectroscopy revealed the binding between ALA and ginsenoside changed the conformation of ALA, which related to different structures and solubility of ligands. Scanning electron microscope illustrated that all ALA-ginsenoside complexes exhibited denser structures via hydrophobic interactions. Additionally, the cytotoxic experiments confirmed that the cytotoxicity of ginsenoside was enhanced after binding with ALA. Molecular docking showed all three ginsenosides were bound to the sulcus depression region of ALA via hydrogen bonding and hydrophobic interaction. Furthermore, molecular dynamics simulation elucidated the precise binding sites and pertinent system properties. Among all three composite systems, 20(S)-Rh2 had optimal binding affinity. These findings enhanced understanding of the synergistic utilization of ALA and ginsenosides as functional ingredients in food, medicine, and cosmetics.
Topics: Ginsenosides; Lactalbumin; Molecular Docking Simulation; Sapogenins
PubMed: 38029562
DOI: 10.1016/j.foodchem.2023.138046