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Recent evidence suggests that both animal and plant proteins support strength and hypertrophy gains when paired with resistance training and adequate protein intake. The purpose of this study was to investigate the effects of supplementary protein source (blend of plant-based [PLNT] vs. animal based [ANML]) to habitual diet on changes in muscle mass and strength in healthy young men undertaking resistance training. Forty-four young untrained males were recruited for this study. Subjects were randomly allocated into two groups, and consumed three 15-g daily doses (45 g. d- total) of either a mixed plant- (i.e.; soy and pea) or animal-based (i.e.; whey) protein in drink form as a supplementary source of protein in their main meals of the day (i.e.; breakfast, lunch, and dinner) for 12 weeks combined with a 3 times/week linear periodized and supervised resistance training program. Prior to the start of the trial, three (2 nonconsecutive weekdays and 1 weekend day) 24-h dietary recalls were collected to determine baseline habitual protein intake and were repeated during the protocol at weeks 4, 8, and 12. Muscle cross-sectional area (CSA, via ultrasonography imaging) determination, body composition (via dual emission x-ray absorptiometry, DXA), and lower-body maximum dynamic strength (1RM, via leg press) were assessed at baseline (PRE) and after 12 weeks of intervention (POST). Both groups showed significant (all  < 0.0001) PRE-to-POST increases in whole-body lean mass (PLNT: 2.4 kg ±1.6, ANML: 2.5 kg ±3.9), appendicular lean mass (PLNT: 1.2 kg ±0.2; ANML: 1.8 kg ±0.2) and leg lean mass (PLNT: 0.9 kg ±0.2; ANML: 1.3 kg ±0.2), vastus lateralis mCSA (PLNT: 0.9 cm ±0.2; ANML: 1.3 cm ±0.2) and leg-press 1RM (PLNT: 64 kg ±7.8; ANML: 63 kg ±7.5), with no between-group differences for any of the variables (all  > 0.05). Complementing dietary protein intake with either a blend of plant- or an animal-based protein similarly supported resistance training-induced muscle adaptations. Distinct Sources of Supplementary Protein in the Resistance Exercise Training-induced Adaptations, NCT05710614, 08/01/2023.

Background: The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1. Objectives: Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1. Methods:Escherichia coli-produced mCyp c 1 was purified using standard chromatographic techniques. Physicochemical properties were investigated by gel electrophoresis, size exclusion chromatography, circular dichroism spectroscopy, reverse-phase high-performance liquid chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural and/or recombinant). GMP-compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and rabbits and for repeated-dose toxicity in mice. Accelerated and real-time protocols were used to evaluate stability of mCyp c 1 as drug substance and drug product. Results: Purified mCyp c 1 behaves as a folded and stable molecule. Using sera of 26 double-blind placebo-controlled food-challenge-proven fish-allergic patients, reduction in allergenic activity ranged from 10- to 5,000-fold (1,000-fold on average), but with retained immunogenicity (immunization in mice/rabbits) and potency to stimulate human PBMCs. Toxicity studies revealed no toxic effects and real-time stability studies on the Al(OH) 3 -adsorbed drug product demonstrated at least 20 months of stability. Conclusion: The GMP drug product developed for treatment of fish allergy has the characteristics targeted for in FAST: i.e. hypoallergenicity with retained immunogenicity. These results have warranted first-in-man immunotherapy studies to evaluate the safety of this innovative vaccine.

Plant-sourced proteins offer environmental and health benefits, and research increasingly includes them in study formulas. However, plant-based proteins have less of an anabolic effect than animal proteins due to their lower digestibility, lower essential amino acid content (especially leucine), and deficiency in other essential amino acids, such as sulfur amino acids or lysine. Thus, plant amino acids are directed toward oxidation rather than used for muscle protein synthesis. In this review, we evaluate the ability of plant- versus animal-based proteins to help maintain skeletal muscle mass in healthy and especially older people and examine different nutritional strategies for improving the anabolic properties of plant-based proteins. Among these strategies, increasing protein intake has led to a positive acute postprandial muscle protein synthesis response and even positive long-term improvement in lean mass. Increasing the quality of protein intake by improving amino acid composition could also compensate for the lower anabolic potential of plant-based proteins. We evaluated and discussed four nutritional strategies for improving the amino acid composition of plant-based proteins: fortifying plant-based proteins with specific essential amino acids, selective breeding, blending several plant protein sources, and blending plant with animal-based protein sources. These nutritional approaches need to be profoundly examined in older individuals in order to optimize protein intake for this population who require a high-quality food protein intake to mitigate age-related muscle loss.

Increased consumption of plant-based foods and decreased consumption of animal-based foods is recommended for healthy diets and sustainable food production. We investigated the effects of partial replacement of dietary animal proteins with plant-based ones on intake of energy-yielding nutrients, fibre, and plasma lipoproteins. This 12-week randomised clinical intervention comprised 107 women and 29 men (20–69 years) in three diet groups with different dietary protein compositions (“ANIMAL”: Animal 70%/plant 30%; “50/50”: Animal 50%/plant 50%; “PLANT”: Animal 30%/plant 70%; all: Protein intake 17 E%). Nutrient intakes were assessed by 4-day food records. Saturated fat intake (E%) was lower and polyunsaturated fatty acid intake (E%) higher in the PLANT and 50/50 groups compared to the ANIMAL group (p < 0.001 for all). Fibre intake was higher in the PLANT (p ˂ 0.001) and 50/50 (p = 0.012) groups. Total and LDL cholesterol were lower in the PLANT than in the ANIMAL group (p = 0.003 for both) but no differences in HDL cholesterol or triglycerides were observed (p > 0.05). Replacing animal protein with plant protein sources in the diet led to an increased fibre intake and improved dietary fat quality as well as blood lipoprotein profile. Flexitarian diets could provide healthy and more sustainable alternatives for the current, predominantly animal-based diets.

Purpose Disproportional fat-free mass loss often occurs post-bariatric surgery, partly due to insufficient protein intake during the post-surgery recovery phase. We compared five protein-enhancing strategies (PES) on patient tolerability, satisfaction and protein intake. Materials and Methods Ninety-four participants, scheduled for bariatric surgery, were enrolled and allocated to either of the following: (1) whey powder, (2) hydrolysed collagen powder, (3) plant-based powder, (4) protein-rich products, (5) protein gel, or control. PES groups were instructed to add 30 g of powder or 2 gels or protein products to their diet. Patient satisfaction and tolerability were evaluated with questionnaires. Dietary intake was assessed prior to and during PES use. Results Seven patients dropped out (i.e. loss of contact, personal reasons or post-surgery complications) yielding an analytical cohort of 87 participants. The majority of patients (61%) did not experience dietary complaints from PES and could use PES ≥ 5 days of the week. PES non-usage was mainly related to taste dislike (58%). Hydrolysed collagen scored highest on tolerability and satisfaction: 86% of the participants could use HC ≥ 5 days and 71% were satisfied with the product. PES increased protein intake from 54.7 ± 21.5 g/day to 64.7 ± 23.4 g/day during the intervention ( p  = 0.002), which differed from the control group (+ 10.1 ± 24.5 g/day vs. − 6.3 ± 23.8 g/day for controls, p  = 0.019). Whey showed the highest increase, namely + 18.3 ± 16.3 g/day ( p  = 0.009). Conclusion PES were tolerated by the majority of participants, and an improved protein intake with PES use was seen. However, the taste of the products could be improved to further enhance satisfaction and tolerability. Graphical Abstract

Whole-body tissue protein turnover is regulated, in part, by the postprandial rise in plasma amino acid concentrations, although minimal data exist on the amino acid response following non-animal-derived protein consumption. We hypothesised that the ingestion of novel plant- and algae-derived dietary protein sources would elicit divergent plasma amino acid responses when compared with vegan- and animal-derived control proteins. Twelve healthy young (male (m)/female (f): 6/6; age: 22 ± 1 years) and 10 healthy older (m/f: 5/5; age: 69 ± 2 years) adults participated in a randomised, double-blind, cross-over trial. During each visit, volunteers consumed 30 g of protein from milk, mycoprotein, pea, lupin, spirulina or chlorella. Repeated arterialised venous blood samples were collected at baseline and over a 5-h postprandial period to assess circulating amino acid, glucose and insulin concentrations. Protein ingestion increased plasma total and essential amino acid concentrations (P < 0·001), to differing degrees between sources (P < 0·001), and the increase was further modulated by age (P < 0·001). Postprandial maximal plasma total and essential amino acid concentrations were highest for pea (2828 ± 106 and 1480 ± 51 µmol·l−1) and spirulina (2809 ± 99 and 1455 ± 49 µmol·l−1) and lowest for chlorella (2053 ± 83 and 983 ± 35 µmol·l−1) (P < 0·001), but were not affected by age (P > 0·05). Postprandial total and essential amino acid availabilities were highest for pea, spirulina and mycoprotein and lowest for chlorella (all P < 0·05), but no effect of age was observed (P > 0·05). The ingestion of a variety of novel non-animal-derived dietary protein sources elicits divergent plasma amino acid responses, which are further modulated by age.

Bioorthogonal chemistry capable of operating in live animals is needed to investigate biological processes such as cell death and immunity. Recent studies have identified a gasdermin family of pore-forming proteins that executes inflammasome-dependent and -independent pyroptosis 1 – 5 . Pyroptosis is proinflammatory, but its effect on antitumour immunity is unknown. Here we establish a bioorthogonal chemical system, in which a cancer-imaging probe phenylalanine trifluoroborate (Phe-BF 3 ) that can enter cells desilylates and ‘cleaves’ a designed linker that contains a silyl ether. This system enabled the controlled release of a drug from an antibody–drug conjugate in mice. When combined with nanoparticle-mediated delivery, desilylation catalysed by Phe-BF 3 could release a client protein—including an active gasdermin—from a nanoparticle conjugate, selectively into tumour cells in mice. We applied this bioorthogonal system to gasdermin, which revealed that pyroptosis of less than 15% of tumour cells was sufficient to clear the entire 4T1 mammary tumour graft. The tumour regression was absent in immune-deficient mice or upon T cell depletion, and was correlated with augmented antitumour immune responses. The injection of a reduced, ineffective dose of nanoparticle-conjugated gasdermin along with Phe-BF 3 sensitized 4T1 tumours to anti-PD1 therapy. Our bioorthogonal system based on Phe-BF 3 desilylation is therefore a powerful tool for chemical biology; our application of this system suggests that pyroptosis-induced inflammation triggers robust antitumour immunity and can synergize with checkpoint blockade. In mouse models of cancer, a biorthogonal chemical system based on desilylation catalysed by phenylalanine trifluoroborate enables the controlled release of gasdermin to induce pyroptosis selectively in tumour cells

Pulmonary arterial hypertension is a progressive disease involving proliferative remodeling of the pulmonary vessels. Despite therapeutic advances, the disease-associated morbidity and mortality remain high. Sotatercept is a fusion protein that traps activins and growth differentiation factors involved in pulmonary arterial hypertension. We conducted a multicenter, double-blind, phase 3 trial in which adults with pulmonary arterial hypertension (World Health Organization [WHO] functional class II or III) who were receiving stable background therapy were randomly assigned in a 1:1 ratio to receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) or placebo every 3 weeks. The primary end point was the change from baseline at week 24 in the 6-minute walk distance. Nine secondary end points, tested hierarchically in the following order, were multicomponent improvement, change in pulmonary vascular resistance, change in N-terminal pro-B-type natriuretic peptide level, improvement in WHO functional class, time to death or clinical worsening, French risk score, and changes in the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Physical Impacts, Cardiopulmonary Symptoms, and Cognitive/Emotional Impacts domain scores; all were assessed at week 24 except time to death or clinical worsening, which was assessed when the last patient completed the week 24 visit. A total of 163 patients were assigned to receive sotatercept and 160 to receive placebo. The median change from baseline at week 24 in the 6-minute walk distance was 34.4 m (95% confidence interval [CI], 33.0 to 35.5) in the sotatercept group and 1.0 m (95% CI, -0.3 to 3.5) in the placebo group. The Hodges-Lehmann estimate of the difference between the sotatercept and placebo groups in the change from baseline at week 24 in the 6-minute walk distance was 40.8 m (95% CI, 27.5 to 54.1; P<0.001). The first eight secondary end points were significantly improved with sotatercept as compared with placebo, whereas the PAH-SYMPACT Cognitive/Emotional Impacts domain score was not. Adverse events that occurred more frequently with sotatercept than with placebo included epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia, and increased blood pressure. In patients with pulmonary arterial hypertension who were receiving stable background therapy, sotatercept resulted in a greater improvement in exercise capacity (as assessed by the 6-minute walk test) than placebo. (Funded by Acceleron Pharma, a subsidiary of MSD; STELLAR ClinicalTrials.gov number, NCT04576988.).

Animal-derived dietary protein ingestion and physical activity stimulate myofibrillar protein synthesis rates in older adults. We determined whether a non-animal-derived diet can support daily myofibrillar protein synthesis rates to the same extent as an omnivorous diet. Nineteen healthy older adults (aged 66 (sem 1) years; BMI 24 (sem 1) kg/m2; twelve males, seven females) participated in a randomised, parallel-group, controlled trial during which they consumed a 3-d isoenergetic high-protein (1·8 g/kg body mass per d) diet, where the protein was provided from predominantly (71 %) animal (OMNI; n 9; six males, three females) or exclusively vegan (VEG; n 10; six males, four females; mycoprotein providing 57 % of daily protein intake) sources. During the dietary control period, participants conducted a daily bout of unilateral resistance-type leg extension exercise. Before the dietary control period, participants ingested 400 ml of deuterated water, with 50-ml doses consumed daily thereafter. Saliva samples were collected throughout to determine body water 2H enrichments, and muscle samples were collected from rested and exercised muscle to determine daily myofibrillar protein synthesis rates. Deuterated water dosing resulted in body water 2H enrichments of approximately 0·78 (sem 0·03) %. Daily myofibrillar protein synthesis rates were 13 (sem 8) (P = 0·169) and 12 (sem 4) % (P = 0·016) greater in the exercised compared with rested leg (1·59 (sem 0·12) v. 1·77 (sem 0·12) and 1·76 (sem 0·14) v. 1·93 (sem 0·12) %/d) in OMNI and VEG groups, respectively. Daily myofibrillar protein synthesis rates did not differ between OMNI and VEG in either rested or exercised muscle (P > 0·05). Over the course of a 3-d intervention, omnivorous- or vegan-derived dietary protein sources can support equivalent rested and exercised daily myofibrillar protein synthesis rates in healthy older adults consuming a high-protein diet.

Abstract Context We compared the efficacy, safety, and effect of 45-day isocaloric very-low-calorie ketogenic diets (VLCKDs) incorporating whey, vegetable, or animal protein on the microbiota in patients with obesity and insulin resistance to test the hypothesis that protein source may modulate the response to VLCKD interventions. Subjects and Methods Forty-eight patients with obesity (19 males and 29 females, homeostatic model assessment (HOMA) index ≥ 2.5, aged 56.2 ± 6.1 years, body mass index [BMI] 35.9 ± 4.1 kg/m2) were randomly assigned to three 45-day isocaloric VLCKD regimens (≤800 kcal/day) containing whey, plant, or animal protein. Anthropometric indexes; blood and urine chemistry, including parameters of kidney, liver, glucose, and lipid metabolism; body composition; muscle strength; and taxonomic composition of the gut microbiome were assessed. Adverse events were also recorded. Results Body weight, BMI, blood pressure, waist circumference, HOMA index, insulin, and total and low-density lipoprotein cholesterol decreased in all patients. Patients who consumed whey protein had a more pronounced improvement in muscle strength. The markers of renal function worsened slightly in the animal protein group. A decrease in the relative abundance of Firmicutes and an increase in Bacteroidetes were observed after the consumption of VLCKDs. This pattern was less pronounced in patients consuming animal protein. Conclusions VLCKDs led to significant weight loss and a striking improvement in metabolic parameters over a 45-day period. VLCKDs based on whey or vegetable protein have a safer profile and result in a healthier microbiota composition than those containing animal proteins. VLCKDs incorporating whey protein are more effective in maintaining muscle performance.