Functional properties of brewer’s spent grain protein isolate. The missing piece in the plant protein portfolio

Plant protein sources, as a part of developing sustainable food systems, are currently of interest globally. Brewer’s spent grain (BSG) is the most plentiful by-product of the brewing industry, representing ~85% of the total side streams produced. Although nutritionally dense, there are very few methods of upcycling these materials. High in protein, BSG can serve as an ideal raw material for protein isolate production. This study details the nutritional and functional characteristics of BSG protein isolate, EverPro, and compares these with the technological performance of the current gold standard plant protein isolates, pea and soy. The compositional characteristics are determined, including amino acid analysis, protein solubility, and protein profile among others. Related physical properties are determined, including foaming characteristics, emulsifying properties, zeta potential, surface hydrophobicity, and rheological properties. Regarding nutrition, EverPro meets or exceeds the requirement of each essential amino acid per g protein, with the exception of lysine, while pea and soy are deficient in methionine and cysteine. EverPro has a similar protein content to the pea and soy isolates, but far exceeds them in terms of protein solubility, with a protein solubility of ~100% compared to 22% and 52% for pea and soy isolates, respectively. This increased solubility, in turn, affects other functional properties; EverPro displays the highest foaming capacity and exhibits low sedimentation activity, while also possessing minimal gelation properties and low emulsion stabilising activity when compared to pea and soy isolates. This study outlines the functional and nutritional properties of EverPro, a brewer’s spent grain protein, in comparison to commercial plant protein isolates, indicating the potential for the inclusion of new, sustainable plant-based protein sources in human nutrition, in particular dairy alternative applications

Barley protein properties, extraction and applications, with a focus on brewers’ spent grain protein

Barley is the most commonly used grain in the brewing industry for the production of beer-type beverages. This review will explore the extraction and application of proteins from barley, particularly those from brewers’ spent grain, as well as describing the variety of proteins present. As brewers’ spent grain is the most voluminous by-product of the brewing industry, the valorisation and utilisation of spent grain protein is of great interest in terms of sustainability, although at present, BSG is mainly sold cheaply for use in animal feed formulations. There is an ongoing global effort to minimise processing waste and increase up-cycling of processing side-streams. However, sustainability in the brewing industry is complex, with an innate need for a large volume of resources such as water and energy. In addition to this, large volumes of a by-product are produced at nearly every step of the process. The extraction and characterisation of proteins from BSG is of great interest due to the high protein quality and the potential for a wide variety of applications, including foods for human consumption such as bread, biscuits and snack-type products

Melanocyte differentiation antigen RAB38/NY-MEL-1 induces frequent antibody responses exclusively in melanoma patients

Expression pattern and immunogenicity are critical issues that define tumor antigens as diagnostic markers and potential targets for immunotherapy. The development of SEREX (serological analysis of recombinant expression libraries) has provided substantial progress in the identification of tumor antigens eliciting both cellular and humoral immune responses in cancer patients. By SEREX, we have previously identified RAB38/NY-MEL-1 as a melanocyte differentiation antigen that is highly expressed in normal melanocytes and melanoma tissues but not in other normal tissues or cancer types. In this study, we further demonstrate that RAB38/NY-MEL-1 is strongly immunogenic, leading to spontaneous antibody responses in a significant proportion of melanoma patients. The immune response occurs solely in malignant melanoma patients and was not detected in patients with other diseases, such as vitiligo, affecting melanocytes. Fine analysis of the spontaneous anti-RAB38/NY-MEL-1 antibody response reveals a polyclonal B cell recognition targeting various epitopes, although a dominant immunogenic region was preferentially recognized. Interestingly, our data indicate that this recognition is not rigid in the course of a patient's response, as the dominant epitope changes during the disease evolution. Implications for the understanding of spontaneous humoral immune responses are discusse

Brewer’s spent yeast (BSY), an underutilized brewing by-product

The repurposing of by-products and the reduction of waste from food processing streams is an ever-increasing area of interest. Brewer’s spent yeast (BSY) is a prevalent by-product of the brewing industry. The spent yeast cells are removed at the end of the bulk fermentation. A small amount of it is used to start the next batch of fermentation; however, the majority of the spent yeast is discarded. This discarded yeast is high in nutrients, in particular proteins, vitamins and minerals, as well as containing functional and biologically active compounds such as polyphenols, antioxidants, β-glucans and mannoproteins. At present, BSY is mainly used in animal feed as a cheap and readily available source of protein. This review explores alternative, value-added applications for brewer’s spent yeast including nutritional ingredients, functional food additives as well as non-food applications. A major challenge in the utilization of BSY in food for human consumption is the high level of RNA. An excess of RNA in the diet can lead to an increase in uric acid in the bloodstream, potentially causing painful health conditions like gout. This issue can be overcome by RNA degradation and removal via additional treatment, namely heat treatment and enzymatic treatment. There is potential for the use of BSY ingredients in various food applications, including meat substitutes, bakery products and savory snacks

Estimation of ontogeny functions for renal transporters using a combined population pharmacokinetic and physiology-based pharmacokinetic approach : application to OAT1,3

To date, information on the ontogeny of renal transporters is limited. Here, we propose to estimate the in vivo functional ontogeny of transporters using a combined population pharmacokinetic (popPK) and physiology-based pharmacokinetic (PBPK) modeling approach called popPBPK. Clavulanic acid and amoxicillin were used as probes for glomerular filtration, combined glomerular filtration, and active secretion through OAT1,3, respectively. The predictive value of the estimated OAT1,3 ontogeny function was assessed by PBPK predictions of renal clearance (CLR) of other OAT1,3 substrates: cefazolin and piperacillin. Individual CL(R)post-hoc values, obtained from a published popPK model on the concomitant use of clavulanic acid and amoxicillin in critically ill children between 1 month and 15 years, were used as dependent variables in the popPBPK analysis. CLR was re-parameterized according to PBPK principles, resulting in the estimation of OAT1,3-mediated intrinsic clearance (CLint,OAT1,3,invivo) and its ontogeny. CLint,OAT1,3,invivo ontogeny was described by a sigmoidal function, reaching half of adult level around 7 months of age, comparable to findings based on renal transporter-specific protein expression data. PBPK-based CLR predictions including this ontogeny function were reasonably accurate for piperacillin in a similar age range (2.5 months-15 years) as well as for cefazolin in neonates as compared to published data (%RMSPE of 21.2 and 22.8%, respectively and %PE within +/- 50%). Using this novel approach, we estimated an in vivo functional ontogeny profile for CLint,OAT1,3,invivo that yields accurate CLR predictions for different OAT1,3 substrates across different ages. This approach deserves further study on functional ontogeny of other transporters

Local treatment of a pleural mesothelioma tumor with ONCOS-102 induces a systemic antitumor CD8(+) T-cell response, prominent infiltration of CD8(+) lymphocytes and Th1 type polarization

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Treatment intensification in HIV-infected Patients is associated With reduced Frequencies of regulatory T cells

In untreated HIV infection, the efficacy of T cell responses decreases over the disease course, resulting in disease progression. The reasons for this development are not completely understood. However, immunosuppressive cells are supposedly crucially involved. Treatment strategies to avoid the induction of these cells preserve immune functions and are therefore the object of intense research efforts. In this study, we assessed the effect of treatment intensification [= 5-drug antiretroviral therapy (ART)] on the development of suppressive cell subsets. The New Era (NE) study recruited patients with primary HIV infection (PHI) or chronically HIV-infected patients with conventional ART (CHI) and applied an intensified 5-drug regimen containing maraviroc and raltegravir for several years. We compared the frequencies of the immune suppressive cells, namely, the myeloid-derived suppressor cells (MDSCs), regulatory B cells (Bregs), and regulatory T cells (Tregs), of the treatment intensification patients to the control groups, especially to the patients with conventional 3-drug ART, and analyzed the Gag/Nef-specific CD8 T cell responses. There were no differences between PHI and CHI in the NE population (p > 0.11) for any of the studied cell types. Polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), monocytic myeloid-derived suppressor cell (M-MDSC), and the Breg frequencies were comparable to those of patients with a 3-drug ART. However, the Treg levels were significantly lower in the NE patients than those in 3ART-treated individuals and other control groups (p = 0.0033). The Gag/Nef-specific CD8 T cell response was broader (p = 0.0134) with a higher magnitude (p = 0.026) in the NE population than that in the patients with conventional ART. However, we did not find a correlation between the frequency of the immune suppressive cells and the interferon-gamma+ CD8 T cell response. In the treatment intensification subjects, the frequencies of the immune suppressive cells were comparable or lower than those of the conventional ART-treated subjects, with surprisingly broad HIV-specific CD8 T cell responses, suggesting a preservation of immune function with the applied treatment regimen. Interestingly, these effects were seen in both treatment intensification subpopulations and were not attributed to the start of treatment in primary infection

Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens

Objectives Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy. Methods Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male). DNA was extracted from whole blood and genotyping for CYP2B6 (516G → T, rs3745274), CAR (540C → T, rs2307424) and PXR (44477T → C, rs1523130; 63396C → T, rs2472677; and 69789A → G, rs763645) was conducted. Binary logistic regression using the backwards method was employed to assess the influence of SNPs and demographics on early discontinuation. Results Of the 373 patients, 131 withdrew from therapy within the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6 516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking status (OR = 0.45; P = 0.002) were associated with discontinuation within 3 months. Conclusions These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these association

Detection of Prion Protein Particles in Blood Plasma of Scrapie Infected Sheep

Prion diseases are transmissible neurodegenerative diseases affecting humans and animals. The agent of the disease is the prion consisting mainly, if not solely, of a misfolded and aggregated isoform of the host-encoded prion protein (PrP). Transmission of prions can occur naturally but also accidentally, e.g. by blood transfusion, which has raised serious concerns about blood product safety and emphasized the need for a reliable diagnostic test. In this report we present a method based on surface-FIDA (fluorescence intensity distribution analysis), that exploits the high state of molecular aggregation of PrP as an unequivocal diagnostic marker of the disease, and show that it can detect infection in blood. To prepare PrP aggregates from blood plasma we introduced a detergent and lipase treatment to separate PrP from blood lipophilic components. Prion protein aggregates were subsequently precipitated by phosphotungstic acid, immobilized on a glass surface by covalently bound capture antibodies, and finally labeled with fluorescent antibody probes. Individual PrP aggregates were visualized by laser scanning microscopy where signal intensity was proportional to aggregate size. After signal processing to remove the background from low fluorescence particles, fluorescence intensities of all remaining PrP particles were summed. We detected PrP aggregates in plasma samples from six out of ten scrapie-positive sheep with no false positives from uninfected sheep. Applying simultaneous intensity and size discrimination, ten out of ten samples from scrapie sheep could be differentiated from uninfected sheep. The implications for ante mortem diagnosis of prion diseases are discussed

Phase I study with ONCOS-102 for the treatment of solid tumors - an evaluation of clinical response and exploratory analyses of immune markers

Peer reviewe