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Case Reports in Genetics 2023The gene encodes megalin (LRP-2/GP330), a large single-spanning transmembrane glycoprotein that serves as a multiligand endocytotic receptor and mediates the...
The gene encodes megalin (LRP-2/GP330), a large single-spanning transmembrane glycoprotein that serves as a multiligand endocytotic receptor and mediates the reabsorption of albumin in the proximal renal tubule. is implicated in an autosomal recessive disorder characterized by dimorphisms, ocular anomalies, sensorineural deafness, proteinuria, epilepsy, and intellectual disability: a clinical condition called Donnai-Barrow syndrome (DBS) or facio-oculo-acoustico-renal (FOAR) syndrome. Pathogenic variants in have been reported in fewer than 60 patients, but a detailed description of seizures, electroencephalographic patterns, imaging findings, behavioral phenotype, and long-term follow-up is still needed. We provide a clinical report of two mono-chorionic twins with -related disease manifesting developmental delay, autistic features, seizures, proteinuria, and sleep disorders. By sequencing clinical exome, candidate rare variants, c.6815G > A, p. (Arg2272His), inherited from the mother and c.12725A > G, p. (Asp4242Gly), inherited from the father, were identified. During follow-up, at the age of 7, the main clinical features of the patients included insomnia, autistic features, severe psychomotor delay, and absent speech. The patients were under treatment with risperidone, antiseizure medications (ASMs), and supplementation of alpha-lactalbumin for self-injury and sleep disturbance. Our study confirmed the wide spectrum of behavioral and neurological and psychiatric features of this rare condition, suggesting new treatment options.
PubMed: 37810913
DOI: 10.1155/2023/6679572 -
Nutrients Jan 2024Shifts toward increased proteolytic fermentation, such as, for example, in athlete and high-protein weight loss diets, may alter the relative abundance of microbial...
Shifts toward increased proteolytic fermentation, such as, for example, in athlete and high-protein weight loss diets, may alter the relative abundance of microbial species in the gut and generate bioactive, potentially deleterious metabolic products. In the current investigation, intestinal (caecal) microbiota composition was studied in rats fed diets differing only in their constituent proteins: milk (casein (CAS), lactalbumin (LA)) or legume () protein isolates (chickpea protein isolate (CPI), lupin protein isolate (LI)). ANOSIM and Discriminant Analysis showed significant ( < 0.05) differences at both family and genus levels in both microbiota composition and functionality as a consequence of feeding the different proteins. Differences were also significant ( < 0.05) for predicted functionality parameters as determined by PICRUSt analysis. LA induced a generally healthier microbiota composition than CAS, and higher amounts of spp. and Methanogenic_PWY were found in the LI group. LEfSe analysis of bacterial composition and functional activities revealed a number of groups/functions able to explain the different effects found with milk and legume protein isolates. In conclusion, the mostly beneficial modulation of intestinal microbiota generally found with legume-based diets is likely to be due, at least in part, to their constituent proteins.
Topics: Humans; Animals; Rats; Gastrointestinal Microbiome; Milk; Diet; Microbiota; Vegetables; Caseins; Lactalbumin; Cicer; Fabaceae; Legumins
PubMed: 38201979
DOI: 10.3390/nu16010149 -
Journal of Dairy Science Apr 2024Xanthine oxidase (XO), a rate-limiting enzyme in uric acid production, is the pivotal therapeutic target for gout and hyperuricemia. In this study, 57 peptides from...
Xanthine oxidase (XO), a rate-limiting enzyme in uric acid production, is the pivotal therapeutic target for gout and hyperuricemia. In this study, 57 peptides from α-lactalbumin and β-lactoglobulin were obtained via virtual enzymatic hydrolysis, and 10 XO inhibitory peptides were virtually screened using molecular docking. Then toxicity, allergenicity, solubility, and isoelectric point of the obtained 10 novel peptides were evaluated by in silico tools. The XO activity of these synthetic peptides was tested using an in vitro assay by high-performance liquid chromatography. Their inhibitory mechanism was further explored by molecular docking. The results showed that 4 peptides GL, PM, AL, and AM exhibited higher inhibitory activity, and their half maximal inhibitory concentration in vitro was 10.20 ± 0.89, 23.82 ± 0.94, 34.49 ± 0.89, and 40.45 ± 0.92 mM, respectively. The peptides fitted well with XO through hydrogen bond, hydrophobic interaction, and van der Waals forces, and amino acid residues Glu802, Leu873, Arg880, and Pro1076 played an important role in this process. Overall, this study indicated 4 novel peptides GL, PM, AL, and AM from whey protein exhibited XO inhibitory activity, and they might be useful and safe XO inhibitors for hyperuricemia prevention and treatment.
Topics: Animals; Gout Suppressants; Hyperuricemia; Xanthine Oxidase; Whey Proteins; Molecular Docking Simulation; Enzyme Inhibitors; Peptides
PubMed: 37923199
DOI: 10.3168/jds.2023-24028 -
Animals : An Open Access Journal From... Feb 2024Prolactin is essential for mammary gland development and lactation. Progesterone also induces ductal branching and alveolar formation via initial secretory...
Prolactin is essential for mammary gland development and lactation. Progesterone also induces ductal branching and alveolar formation via initial secretory differentiation within the mammary gland. Herein, we aimed to evaluate the role of progesterone as a prolactin substitute for the production of cell-cultured milk components in MAC-T cells. Cells were treated with various hormones such as prolactin (PRL), progesterone (P4), 17β-estradiol (E2), cortisol (COR), and insulin (INS) for 5 d. MAC-T cells cultured in a P4 differentiation media (2500 ng/mL of P4, 25 ng/mL of E2, 25 ng/mL of COR, and 25 ng/mL of INS) showed similar levels of E74-like factor 5 (Elf5) and milk component synthesis (-casein, -casein, -lactalbumin, β-lactoglobulin, and triglycerides) compared to those cultured in a PRL differentiation media (5000 ng/mL of PRL, 500 ng/mL of CORT, and 50 ng/mL of INS). The levels of -casein and triglycerides in the optimal P4 differentiation media were present at comparable levels to those in the PRL differentiation media. Our results demonstrated that P4 induces the activation of Elf5 and the synthesis of milk components in MAC-T cells, similar to PRL. Therefore, P4 may be used as an effective substitute of PRL for cell-cultured milk production in in vitro frameworks.
PubMed: 38396610
DOI: 10.3390/ani14040642 -
Foods (Basel, Switzerland) Feb 2024The objective of this work was to study the influence of three dietary fibre fractions (pectin, gum arabic and cellulose) and three protein fractions (casein,...
The objective of this work was to study the influence of three dietary fibre fractions (pectin, gum arabic and cellulose) and three protein fractions (casein, lactalbumin and soy) on the trace element bioaccessibility (Fe, Mn, Ni, Se and Zn) of turnip tops ( subsp. ) growing under Mediterranean conditions. Then, it aimed to promote the use of this vegetable not only for direct fresh consumption but also as a main ingredient in the development of food mixtures. The results showed that soluble fibre fractions, such as pectin and gum arabic, can enhance the bioaccessibility of trace elements, such as Fe, Mn, Se and Zn. This effect was not proved for cellulose (an insoluble fibre fraction), in which, at best, no bioaccessibility effect was observed. Regarding the protein fractions, with the exception of Se, caseins and lactalbumin had a neutral effect on improving the trace element bioaccessibility. This did not hold true for soy protein, in which a considerable improvement in the bioaccessibility of Fe, Mn, Se and Zn was determined.
PubMed: 38338598
DOI: 10.3390/foods13030462 -
Scientific Reports Feb 2024Though new targeted therapies for colorectal cancer, which progresses from local intestinal tumors to metastatic disease, are being developed, tumor specificity remains...
Though new targeted therapies for colorectal cancer, which progresses from local intestinal tumors to metastatic disease, are being developed, tumor specificity remains an important problem, and side effects a major concern. Here, we show that the protein-fatty acid complex BAMLET (bovine alpha-lactalbumin made lethal to tumor cells) can act as a peroral treatment for colorectal cancer. Apc mice, which carry mutations relevant to hereditary and sporadic human colorectal cancer, that received BAMLET in the drinking water showed long-term protection against tumor development and decreased expression of tumor growth-, migration-, metastasis- and angiogenesis-related genes. BAMLET treatment via drinking water inhibited the Wnt/β-catenin and PD-1 signaling pathways and prolonged survival without evidence of toxicity. Systemic disease in the lungs, livers, spleens, and kidneys, which accompanied tumor progression, was inhibited by BAMLET treatment. The metabolic response to BAMLET included carbohydrate and lipid metabolism, which were inhibited in tumor prone Apc mice and weakly regulated in C57BL/6 mice, suggesting potential health benefits of peroral BAMLET administration in addition to the potent antitumor effects. Together, these findings suggest that BAMLET administration in the drinking water maintains antitumor pressure by removing emergent cancer cells and reprogramming gene expression in intestinal and extra-intestinal tissues.
Topics: Mice; Humans; Animals; Cattle; Drinking Water; Mice, Inbred C57BL; Signal Transduction; Colorectal Neoplasms; beta Catenin
PubMed: 38360830
DOI: 10.1038/s41598-024-54040-w -
Current Research in Food Science 2024Partially replacing animal proteins with plant proteins to develop new products has much attention. To get knowledge of their application in emulsion gels, heat-induced...
Partially replacing animal proteins with plant proteins to develop new products has much attention. To get knowledge of their application in emulsion gels, heat-induced composite protein emulsion gels were fabricated using the mixtures of whey protein isolate (WPI) and soy protein isolate (SPI) with the final total protein concentration of 10% (w/w). The water holding capacity (WHC), mechanical and rheological properties and microstructure of mixed protein emulsion gels prepared at different WPI to SPI ratios (100:0, 90:10, 70:30, 50:50, 30:70, 10:90, 0:100, w/w) were investigated. The ratios of WPI to SPI showed little effect on the WHC of the mixed protein emulsion gels (p > 0.05). Increasing the ratio of SPI decreased the hardness and storage modulus (G') of mixed protein emulsion gels, whereas the porosity of mixed protein emulsion gels in the microstructure increased, as shown by CLSM. Both β-lactoglobulin and α-lactalbumin from WPI and 7 S and 11 S from SPI participated in forming the gel matrix of mixed protein emulsion gels. More protein aggregates existed as the gel matrix filler at the high soy protein levels. Interestingly, the G' of mixed protein emulsion gels at the WPI to SPI ratio of 50:50 was higher than the sum of G' of individual WPI and SPI emulsion gels. The whey protein network predominated the gel matrix, while soy protein predominated in the active filling effect. When subjected to an in vitro dynamic gastric digestion model, soy protein in the gels (WPI:SPI = 50:50) degraded faster than whey protein during gastric digestion. This study provided new information on the characteristics of composite protein emulsion gel fabricated with the WPI and SPI mixture.
PubMed: 38283161
DOI: 10.1016/j.crfs.2023.100674 -
Asian Pacific Journal of Allergy and... Jan 2024Cow's milk allergy (CMA) is one of the most common food allergies in young children. As improved diagnostic tools, allergic tests are inconsistent and limited in...
BACKGROUND
Cow's milk allergy (CMA) is one of the most common food allergies in young children. As improved diagnostic tools, allergic tests are inconsistent and limited in predicting anaphylaxis.
OBJECTIVE
To explore risk factors for anaphylaxis and to determine practical cut-offs for allergic tests in predicting anaphylaxis.
METHODS
This is a prospective cohort study. Children with IgE-mediated CMA were enrolled and divided into three groups (Group 1: non-anaphylaxis; Group 2: GRADE I anaphylaxis; Group 3: GRADE II-IV anaphylaxis that warranted epinephrine). Prick-to-prick tests (PTPs) using fresh cow's milk (CM) were performed. Serum specific IgE (sIgE) against CM and its components, including casein, alpha-lactalbumin, beta-lactoglobulin, and bovine serum albumin were measured. The 90% and 95% positive predictive value (PPV) decision points for predicting anaphylaxis were determined. Potential predictors of anaphylaxis were evaluated in logistic regression models.
RESULTS
This study included 134 CMA patients with a median age of 14.4 months. The sensitization rate to any CM component was 89%. Group 3 was more likely to be sensitized to multiple CM components and have higher sIgE levels. The 95% PPV diagnostic decision points of casein-sIgE in predicting anaphylaxis was 13.0 kUA/L. For GRADE II-IV anaphylaxis, casein-sIgE ≥ 54.9 kUA/L could provide a PPV of 88.9%. The elevated casein-sIgE level (OR 14.0, P=0.025) and complicating respiratory allergic diseases (OR 4.8, P=0.022) were independent risk factors for GRADE II-IV anaphylaxis.
CONCLUSION
High casein-sIgE levels are strongly associated with CM anaphylaxis. Detection of casein-sIgE may offer an additional value for the prediction of CM anaphylaxis.
PubMed: 38183641
DOI: 10.12932/AP-010823-1667