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European Review For Medical and... Apr 2021This open-label non-randomized clinical study aimed at evaluating the effects of myo-inositol plus alpha-lactalbumin in two groups of PCOS women, treated in Mexico and... (Clinical Trial)
Clinical Trial
OBJECTIVE
This open-label non-randomized clinical study aimed at evaluating the effects of myo-inositol plus alpha-lactalbumin in two groups of PCOS women, treated in Mexico and Italy. Alpha-lactalbumin was used being effective in increasing myo-inositol intestinal absorption. This effect is very useful in greatly reducing the therapeutic failure of myo-inositol in some patients (inositol resistant subjects).
PATIENTS AND METHODS
The study involved 34 normal weight or overweight patients (14 in Mexico and 20 in Italy), aged 18 to 40 years, with anovulation and infertility > 1 year and insulin resistance diagnosed by HOMA-Index. Patients were administered orally with 2 g myo-inositol, 50 mg alpha-lactalbumin, and 200 µg of folic acid twice a day for 6 months. Controls were the same patients at t0 (baseline). The primary outcome was HOMA-index decrease after 3 and 6 months of treatment. Other parameters monitored were BMI, progesterone, LH, FSH, total testosterone, free testosterone, androstenedione, total cholesterol, HDL, LDL, triglycerides.
RESULTS
Recovery was general, and its relevance was higher when the starting point was further away from the normal range. The most important results were obtained with insulin, HOMA-index, LH, and androstenedione. No significant adverse effects were detected in both groups of patients.
CONCLUSIONS
This clinical trial demonstrated for the first time that myo-inositol and alpha-lactalbumin improve important parameters in PCOS patients characterized by different metabolic profiles.
Topics: Adolescent; Adult; Female; Humans; Inositol; Italy; Lactalbumin; Mexico; Overweight; Polycystic Ovary Syndrome; Young Adult
PubMed: 33928619
DOI: 10.26355/eurrev_202104_25743 -
Nutrition Reviews Jul 2015Milk represents a unique resource for translational medicine: It contains a rich pool of biologically active molecules with demonstrated clinical benefits. The ongoing... (Review)
Review
Milk represents a unique resource for translational medicine: It contains a rich pool of biologically active molecules with demonstrated clinical benefits. The ongoing characterization of the mechanistic process through which milk components promote development and immunity has revealed numerous milk-derived compounds with potential applications as clinical therapies in infectious and inflammatory disease, cancer, and other conditions. Lactoferrin is an effective antimicrobial and antiviral agent in high-risk patient populations and a potentially potent adjuvant to chemotherapy in lung cancer. Enteric nutrition formulas supplemented with transforming growth factor β, a milk cytokine, have been shown to promote remission in pediatric Crohn's disease. A number of milk glycans, including human milk oligosaccharides, show promise in preclinical studies as antimicrobial and anti-inflammatory agents. While active preclinical investigations of human milk may soon result in large-scale production of human milk molecules, bovine milk components in many instances represent a practical source of bioactive milk compounds for use in clinical trials. This review summarizes current efforts to translate the compounds derived from human and bovine milk into effective clinical therapies. These efforts suggest a common pathway for the translation of milk-derived compounds into clinical applications.
Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Caseins; Cattle; Cell Line, Tumor; Crohn Disease; Humans; Lactalbumin; Lactoferrin; Milk; Milk, Human; Oligosaccharides; Randomized Controlled Trials as Topic; Transforming Growth Factor beta
PubMed: 26011900
DOI: 10.1093/nutrit/nuv009 -
Nutrients Jan 2020Human milk is rich in nutritional factors, such as alpha-lactalbumin (α-Lac), and important for neonatal development, but nutrient supplementation may be required for...
Human milk is rich in nutritional factors, such as alpha-lactalbumin (α-Lac), and important for neonatal development, but nutrient supplementation may be required for optimal growth. Using a pig model, we hypothesized that α-Lac-enriched whey protein concentrate (WPC) supplementation improves neonatal development. Cesarean-delivered preterm pigs were fed either dilute bovine milk (REF) or REF milk supplemented with WPC with normal (STANDARD-ALPHA) or high (HIGH-ALPHA) α-Lac. Clinical, gut, immune and cognitive endpoints (open field, T-maze) were assessed and tissues collected at Day 19. The growth of STANDARD-ALPHA and HIGH-ALPHA were higher than REF (31 vs. 19 g/kg/d). Most organ weights, gut, immunity and brain variables were similar between WPC groups. HIGH-ALPHA had a higher bone mineral content, colon microbial diversity and an abundance of specific bacteria and microbial metabolites, and tended to show a faster food transit time ( = 0.07). Relative to REF, WPC pigs showed higher relative organ weights, blood amino acids, blood neutrophil function, and microbial metabolites, but lower brush-border enzyme activities and plasma cortisol. Cognition outcomes did not differ among the groups. In conclusion, WPC supplementation of milk improved some growth, gut and immunity parameters in preterm pigs. However, increasing the α-Lac content beyond human milk levels had limited effects on the immature gut and developing brain.
Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Behavior, Animal; Brain; Cognition; Food, Formulated; Gastrointestinal Microbiome; Gestational Age; Immune System; Intestines; Lactalbumin; Nutritional Status; Nutritive Value; Sus scrofa; Whey Proteins
PubMed: 31963562
DOI: 10.3390/nu12010245 -
Journal of Food Science Oct 2021Whey is an abundantand sustainable source of bioactive peptides obtained from cheese making process. Whey proteins such as α-lactalbumin can be biologically active when...
Whey is an abundantand sustainable source of bioactive peptides obtained from cheese making process. Whey proteins such as α-lactalbumin can be biologically active when the bioactive peptides encrypted in the amino acid sequence of the native protein are released by enzymatic hydrolysis. In the present work, the identification, sequence analysis, and antioxidant activity of bioaccessible peptides from α-lactalbumin alcalase-hydrolysate was assessed. Antioxidant activity (ABTS, ORAC, and HORAC) of α-lactalbumin showed a significant increase (p < 0.05) after the enzymatic treatment with alcalase and this capacity increased even more after the simulation of the gastrointestinal digestion process. Peptides contained in the gastrointestinal digest of α-lactalbumin hydrolysate were separated by preparative RP-HPLC (55 fractions), and three peptides were identified by LC-MS/MS analysis from selected fractions: IWCKDDQNPH (MW: 1254.54 Da) f(59-68), KFLDDDLTDDIM (MW: 1439.64 Da) f(79-90), DKFLDDDLTDDIM (MW: 1554.67 Da) f(78-90). Among the chemically synthesized peptides, IWCKDDQNPH showed the highest antioxidant capacity determined by ORAC, ABTS, and HORAC assays (IC 0.015 ± 0.002, 0.45 ± 0.02, and 1.30 ± 0.05 mg/ml, respectively) and this activity may be related to the amino acid sequence. This is the first report where these bioaccessible peptides from α-lactalbumin hydrolysate were identified. The α-lactalbumin hydrolysate could be employed as a functional antioxidant ingredient. PRACTICAL APPLICATION: The present work studied the bioaccessibility of antioxidant peptides from an α-lactalbumin alcalase-hydrolysate by identifying three novel bioaccessible peptides responsible for the antioxidant capacity, providing evidence of the hydrolysate potential as an antioxidant ingredient in the formulations of functional foods and/or food supplements.
Topics: Antioxidants; Chromatography, Liquid; Food Analysis; Hydrolysis; Lactalbumin; Peptides; Tandem Mass Spectrometry
PubMed: 34549457
DOI: 10.1111/1750-3841.15918 -
Molecules (Basel, Switzerland) Oct 2021In complex foods, bioactive secondary plant metabolites (SPM) can bind to food proteins. Especially when being covalently bound, such modifications can alter the...
In complex foods, bioactive secondary plant metabolites (SPM) can bind to food proteins. Especially when being covalently bound, such modifications can alter the structure and, thus, the functional and biological properties of the proteins. Additionally, the bioactivity of the SPM can be affected as well. Consequently, knowledge of the influence of chemical modifications on these properties is particularly important for food processing, food safety, and nutritional physiology. As a model, the molecular structure of conjugates between the bioactive metabolite benzyl isothiocyanate (BITC, a hydrolysis product of the glucosinolate glucotropaeolin) and the whey protein α-lactalbumin (α-LA) was investigated using circular dichroism spectroscopy, anilino-1-naphthalenesulfonic acid fluorescence, and dynamic light scattering. Free amino groups were determined before and after the BITC conjugation. Finally, mass spectrometric analysis of the BITC-α-LA protein hydrolysates was performed. As a result of the chemical modifications, a change in the secondary structure of α-LA and an increase in surface hydrophobicity and hydrodynamic radii were documented. BITC modification at the ε-amino group of certain lysine side chains inhibited tryptic hydrolysis. Furthermore, two BITC-modified amino acids were identified, located at two lysine side chains (K32 and K113) in the amino acid sequence of α-LA.
Topics: Amino Acid Sequence; Animals; Cattle; Circular Dichroism; Food Handling; Food Safety; Humans; Hydrodynamics; Hydrophobic and Hydrophilic Interactions; Isothiocyanates; Lactalbumin; Models, Molecular; Molecular Structure; Peptide Fragments; Protein Stability; Protein Structure, Secondary; Proteolysis; Tandem Mass Spectrometry
PubMed: 34684828
DOI: 10.3390/molecules26206247 -
ACS Chemical Neuroscience Apr 2022Parkinson's disease (PD) is the second most common devastating neurodegenerative disorder. Presently used therapies for PD have severe side effects and are limited to...
Parkinson's disease (PD) is the second most common devastating neurodegenerative disorder. Presently used therapies for PD have severe side effects and are limited to only temporary improvement. Therefore, a new therapeutic approach to treat PD urgently needs to be developed. α-Lactalbumin, the most abundant milk protein in camel milk, has been attributed to various medicinal properties. This study intended to investigate the neuroprotective efficacy of the camel α-lactalbumin and oleic acid (CLOA) complex. One mechanism postulated to underlie neuroprotection by the CLOA complex is the induction of silent information regulatory protein (SIRT1). SIRT1 is known to be involved in several pathological and physiological processes, and it has been suggested that SIRT1 plays a protective role in PD. Oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis are involved in PD pathogenesis. Our results revealed that SIRT1 inhibits oxidative stress by maintaining HIF-1α in a deacetylated state. SIRT1 upregulates the expression of FOXO3a and HSF-1, thus inhibiting apoptosis and maintaining the homeostasis of cellular proteins. Increased SIRT1 expression reduces the levels of TNF-α, IL-6, and IL-8, which in turn inhibits neuroinflammation. In addition to SIRT1, the CLOA complex also enhances the expression of survivin and leptin and promotes the survival of neuroblastoma cells. Altogether, our results suggest that the CLOA complex might be a novel therapeutic molecule that could ameliorate neuronal cell damage in PD.
Topics: Animals; Camelus; Lactalbumin; Neuroprotection; Neuroprotective Agents; Oleic Acid; Oxidative Stress; Parkinson Disease; Rotenone; Sirtuin 1
PubMed: 35385250
DOI: 10.1021/acschemneuro.1c00876 -
Journal of Dairy Science Dec 2020Camel milk has unique physical, nutritional, and technological properties when compared with other milks, especially bovine. Because proteins confer many of the... (Comparative Study)
Comparative Study
Camel milk has unique physical, nutritional, and technological properties when compared with other milks, especially bovine. Because proteins confer many of the properties of milk and its products, this study aimed to determine the proteins of camel milk, their correlations, and relative distribution. Raw milk samples were collected from 103 dromedary camels in the morning and evening. Capillary electrophoresis results showed wide variation in the concentrations (g/L) of proteins between samples as follows: α-lactalbumin, 0.3 to 2.9; α-casein, 2.4 to 10.3; α-casein, 0.3 to 3.9; β-casein, 5.5 to 29.0; κ-casein, 0.1 to 2.4; unknown casein protein 1, 0.0 to 3.4; and unknown casein protein 2, 0.0 to 4.6. The range in percent composition of the 4 caseins were as follows: α, 12.7 to 35.3; α, 1.8 to 20.8; β, 42.3 to 77.4; and κ, 0.6 to 17.4. The relative proportion of α-, α-, β-, and κ-caseins in camel milk (26:4:67:3, wt/wt) differed from that of bovine milk (38:10:36:12, wt/wt). This difference might explain the dissimilarity between the 2 milks with respect to technical and nutritional properties.
Topics: Animals; Camelus; Caseins; Cattle; Electrophoresis, Capillary; Lactalbumin; Milk; Milk Proteins; Nutritive Value; Species Specificity
PubMed: 33069408
DOI: 10.3168/jds.2020-19122 -
International Journal of Biological... Sep 2021To clarify the mechanism of semicarbazide-modified α-lactalbumin (SEM-LA)-mediated cytotoxicity, we investigated its effect on human U937 leukemia cells and MCF-7...
To clarify the mechanism of semicarbazide-modified α-lactalbumin (SEM-LA)-mediated cytotoxicity, we investigated its effect on human U937 leukemia cells and MCF-7 breast cancer cells in the current study. SEM-LA induced apoptosis in U937 cells, which showed increased NOX4 expression, procaspase-8 degradation, and t-Bid production. FADD depletion inhibited SEM-LA-elicited caspase-8 activation, t-Bid production, and cell death, indicating that SEM-LA activated death receptor-mediated apoptosis in U937 cells. SEM-LA stimulated Ca-mediated Akt activation, which in turn increased Sp1- and p300-mediated NOX4 transcription. The upregulation of NOX4 expression promoted ROS-mediated p38 MAPK phosphorylation, leading to protein phosphatase 2A (PP2A)-regulated tristetraprolin (TTP) degradation. Remarkably, TTP downregulation increased the stability of TNF-α mRNA, resulting in the upregulation of TNF-α protein expression. Abolishment of Ca-NOX4-ROS axis-mediated p38 MAPK activation attenuated SEM-LA-induced TNF-α upregulation and protected U937 cells from SEM-LA-mediated cytotoxicity. The restoration of TTP expression alleviated the effect of TNF-α upregulation and cell death induced by SEM-LA. Altogether, the data in this study demonstrate that SEM-LA activates TNF-α-mediated apoptosis in U937 cells through the NOX4/p38 MAPK/PP2A axis. We think that a similar pathway can also explain the death of MCF-7 human breast cancer cells after SEM-LA treatment.
Topics: Antineoplastic Agents; Apoptosis; Apoptosis Regulatory Proteins; Breast Neoplasms; Calcium Signaling; E1A-Associated p300 Protein; Female; Humans; Lactalbumin; Leukemia; MCF-7 Cells; NADPH Oxidase 4; Protein Phosphatase 2; Proteolysis; Reactive Oxygen Species; Semicarbazides; Sp1 Transcription Factor; Tristetraprolin; Tumor Necrosis Factor-alpha; U937 Cells; p38 Mitogen-Activated Protein Kinases
PubMed: 34310992
DOI: 10.1016/j.ijbiomac.2021.07.133 -
Biochimica Et Biophysica Acta. General... May 2019The interaction between proteins and membranes is of great interest in biomedical and biotechnological research for its implication in many functional and dysfunctional...
The interaction between proteins and membranes is of great interest in biomedical and biotechnological research for its implication in many functional and dysfunctional processes. We present an experimental study on the interaction between model membranes and alpha-lactalbumin (α-La). α-La is widely studied for both its biological function and its anti-tumoral properties. We use advanced fluorescence microscopy and spectroscopy techniques to characterize α-La-membrane mechanisms of interaction and α-La-induced modifications of membranes when insertion of partially disordered regions of protein chains in the lipid bilayer is favored. Moreover, using fluorescence lifetime imaging, we are able to distinguish between protein adsorption and insertion in the membranes. Our results indicate that, upon addition of α-La to giant vesicles samples, protein is inserted into the lipid bilayer with rates that are concentration-dependent. The formation of heterogeneous hybrid protein-lipid co-aggregates, paralleled with protein conformational and structural changes, alters the membrane structure and morphology, leading to an increase in membrane fluidity.
Topics: Adsorption; Animals; Cattle; Fluorescent Dyes; Humans; Lactalbumin; Lipid Bilayers; Lipids; Membrane Lipids; Protein Conformation; Spectrometry, Fluorescence
PubMed: 30742952
DOI: 10.1016/j.bbagen.2019.02.005 -
Food Chemistry Jul 2019The effects of high pressure processing on the binding interactions of α-lactalbumin and pelargonidin-3-glucoside were studied using the fluorescence quenching,...
The effects of high pressure processing on the binding interactions of α-lactalbumin and pelargonidin-3-glucoside were studied using the fluorescence quenching, molecular dynamic simulation and molecular docking analysis. The results of fluorescence quenching indicated that the high pressure processing significantly increased the quenching constants of α-lactalbumin at pH 7.4 and pH 8.0. The accessible fraction at pH 8.0 was significantly increased, while the fractions at pH 6.0 and pH 7.4 were increased without significant difference. Molecular dynamic simulation and docking results demonstrated that the coil structures and locations, and the residues structures in the binding site of α-lactalbumin were affected, the binding site was the typical binding site of calcium ion and not changed during the processing. The dissociation constant of histidine residues was in the range of 6.13 to 6.83, the charge on the residues increased when pH value increased, affected the binding interactions and caused the quenching constant difference.
Topics: Animals; Anthocyanins; Binding Sites; Hydrogen-Ion Concentration; Lactalbumin; Molecular Docking Simulation; Molecular Dynamics Simulation; Pressure; Protein Binding; Protein Structure, Tertiary; Spectrometry, Fluorescence
PubMed: 30797338
DOI: 10.1016/j.foodchem.2019.01.129