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Background/objectives: Hypertension affects about 30% of adults worldwide. Garlic has blood pressure-lowering properties and the mechanism of action is biologically plausible. Our trial assessed the effect, dose–response, tolerability and acceptability of different doses of aged garlic extract as an adjunct treatment to existing antihypertensive medication in patients with uncontrolled hypertension. Subjects/methods: A total of 79 general practice patients with uncontrolled systolic hypertension participated in a double-blind randomised placebo-controlled dose–response trial of 12 weeks. Participants were allocated to one of three garlic groups with either of one, two or four capsules daily of aged garlic extract (240/480/960 mg containing 0.6/1.2/2.4 mg of S -allylcysteine) or placebo. Blood pressure was assessed at 4, 8 and 12 weeks and compared with baseline using a mixed-model approach. Tolerability was monitored throughout the trial and acceptability was assessed at 12 weeks by questionnaire. Results: Mean systolic blood pressure was significantly reduced by 11.8±5.4 mm Hg in the garlic-2-capsule group over 12 weeks compared with placebo ( P =0.006), and reached borderline significant reduction in the garlic-4-capsule group at 8 weeks (−7.4±4.1 mm Hg, P =0.07). Changes in systolic blood pressure in the garlic-1-capsule group and diastolic blood pressure were not significantly different to placebo. Tolerability, compliance and acceptability were high in all garlic groups (93%) and highest in the groups taking one or two capsules daily. Conclusions: Our trial suggests aged garlic extract to be an effective and tolerable treatment in uncontrolled hypertension, and may be considered as a safe adjunct treatment to conventional antihypertensive therapy.

The purpose of the present study was to examine the effect of a cysteine-rich whey protein (Immunocal®) supplementation in combination with resistance training on muscle strength and lean body mass (LBM) in elderly individuals. We hypothesized that the cysteine-rich whey protein (Immunocal®) group would experience a greater increase in muscle strength and lean body mass versus the control group (casein). Randomized double-blind controlled intervention study. Institut de Recherches Cliniques de Montréal in Montreal, Canada. Ninety-nine non-frail elderly subjects were recruited. Participants were randomly assigned into two groups. The experimental group received a cysteine-rich whey protein isolate (Immunocal®) (20 g/day) and the control group received casein (20 g/day) during a 135-day period. In addition, both groups performed the same resistance training program (3 times per week). Body composition (DXA) and muscle strength (leg press) were measured. Of the 99 recruited participants, 84 completed the 135-day study period. Of these, 67 subjects (33 in the casein group and 34 in the Immunocal® group) complied and used at least 80 % of the study product and completed at least 80 % of their training sessions. Results in this selected group show an increase in all three muscle strength variables (absolute, normalized by BW and by LBM) by 31.0 %, 30.9 % and 30.0 %, respectively in the casein group as well as 39.3 %, 39.9 % and 43.3 %, respectively in the Immunocal® group after the intervention (p < 0.05). The increases in muscle strength favored Immunocal® versus casein by approximately 10 % when expressed in kg per kg BW and in kg per kg LBM (p < 0.05). No significant changes were found between pre-and-post intervention in both groups for total LBM. Our findings showed increases in muscle strength in both groups after resistance training, however, significant additional increases were observed in muscle strength with the addition of a cysteine-rich whey protein (Immunocal®) versus casein.

Cysteine modifications emerge as important players in cellular signaling and homeostasis. Here, we present a chemical proteomics strategy for quantitative analysis of reversibly modified Cysteines using bioorthogonal cleavable-linker and switch technique (Cys-BOOST). Compared to iodoTMT for total Cysteine analysis, Cys-BOOST shows a threefold higher sensitivity and considerably higher specificity and precision. Analyzing S-nitrosylation (SNO) in S-nitrosoglutathione (GSNO)-treated and non-treated HeLa extracts Cys-BOOST identifies 8,304 SNO sites on 3,632 proteins covering a wide dynamic range of the proteome. Consensus motifs of SNO sites with differential GSNO reactivity confirm the relevance of both acid-base catalysis and local hydrophobicity for NO targeting to particular Cysteines. Applying Cys-BOOST to SH-SY5Y cells, we identify 2,151 SNO sites under basal conditions and reveal significantly changed SNO levels as response to early nitrosative stress, involving neuro(axono)genesis, glutamatergic synaptic transmission, protein folding/translation, and DNA replication. Our work suggests SNO as a global regulator of protein function akin to phosphorylation and ubiquitination. Reversible cysteine modifications play important roles in cellular redox signaling. Here, the authors develop a chemical proteomics strategy that enables the quantitative analysis of endogenous cysteine nitrosylation sites and their dynamic regulation under nitrosative stress conditions.

S-nitrosylation, the selective posttranslational modification of protein cysteine residues to form S-nitrosocysteine, is one of the molecular mechanisms by which nitric oxide influences diverse biological functions. In this study, unique MS-based proteomic approaches precisely pinpointed the site of S-nitrosylation in 328 peptides in 192 proteins endogenously modified in WT mouse liver. Structural analyses revealed that S-nitrosylated cysteine residues were equally distributed in hydrophobic and hydrophilic areas of proteins with an average predicted pK a of 10.01 ± 2.1. S-nitrosylation sites were over-represented in α-helices and under-represented in coils as compared with unmodified cysteine residues in the same proteins (χ² test, P < 0.02). A quantile—quantile probability plot indicated that the distribution of S-nitrosocysteine residues was skewed toward larger surface accessible areas compared with the unmodified cysteine residues in the same proteins. Seventy percent of the S-nitrosylated cysteine residues were surrounded by negatively or positively charged amino acids within a 6-Å distance. The location of cysteine residues in α-helices and coils in highly accessible surfaces bordered by charged amino acids implies site directed S-nitrosylation mediated by protein—protein or small molecule interactions. Moreover, 13 modified cysteine residues were coordinated with metals and 15 metalloproteins were endogenously modified supporting metal-catalyzed S-nitrosylation mechanisms. Collectively, the endogenous S-nitrosoproteome in the liver has structural features that accommodate multiple mechanisms for selective site-directed S-nitrosylation.

Aging is the primary risk factor for the development of numerous human chronic diseases. On a molecular level, it significantly impacts the regulation of protein modifications, leading to the accumulation of degenerative protein modifications (DPMs) such as aberrant serine phosphorylation (p‐Ser) and trioxidized cysteine (t‐Cys) within the proteome. The altered p‐Ser is linked to abnormal cell signaling, while the accumulation of t‐Cys is associated with chronic diseases induced by oxidative stress. Despite this, the potential cross‐effects and functional interplay between these two critical molecular factors of aging remain undisclosed. This study analyzes the aging proteome of wild‐type C57BL/6NTac mice over 2 years using advanced proteomics and bioinformatics. Our objective is to provide a comprehensive analysis of how t‐Cys affects cell signaling and protein structure in the aging process. The results obtained indicate that t‐Cys residues accumulate in the aging proteome, interact with p‐Ser interacting enzymes, as validated in vitro, and alter their structures similarly to p‐Ser. These findings have significant implications for understanding the interplay of oxidative stress and phosphorylation in the aging process. Additionally, they open new venues for further research on the role(s) of these protein modifications in various human chronic diseases and aging, wherein exacerbated oxidation and aberrant phosphorylation are implicated. Trioxidized cysteine, product of cellular prooxidant processes, demonstrates an age‐related increase in various mammalian proteomes. These post‐translationally modified residues exhibit the capacity to interact with enzymes that mediate phosphorylation signaling, mimicking features of phosphorylated serine residues and likely contributing to the alteration of cell signaling during aging. Additionally, we demonstrate that phosphorylation‐linked kinase activity becomes modulated in an oxidation‐dependent manner.

Cysteine is the most intrinsically nucleophilic amino acid in proteins, where its reactivity is tuned to perform diverse biochemical functions. The absence of a consensus sequence that defines functional cysteines in proteins has hindered their discovery and characterization. Here we describe a proteomics method to profile quantitatively the intrinsic reactivity of cysteine residues en masse directly in native biological systems. Hyper-reactivity was a rare feature among cysteines and it was found to specify a wide range of activities, including nucleophilic and reductive catalysis and sites of oxidative modification. Hyper-reactive cysteines were identified in several proteins of uncharacterized function, including a residue conserved across eukaryotic phylogeny that we show is required for yeast viability and is involved in iron-sulphur protein biogenesis. We also demonstrate that quantitative reactivity profiling can form the basis for screening and functional assignment of cysteines in computationally designed proteins, where it discriminated catalytically active from inactive cysteine hydrolase designs. The cysteines that really count Cysteine residues are often active in the catalytic or regulatory sites of proteins because of the extremely nucleophilic nature of their thiol side chains. Side-chain reactivity varies widely depending on the local protein micro-environment, but a new technique termed 'quantitative reactivity profiling', combining activity-based small-molecule probes with mass spectrometry, makes it possible to measure the intrinsic reactivity of cysteine residues. Hyper-reactive cysteines were identified in several proteins of unknown function, including a residue conserved across eukaryotes that is required for yeast viability and is involved in iron-sulphur protein biogenesis. Cysteine is the most intrinsically nucleophilic amino acid in proteins, but the absence of a consensus sequence that defines functional cysteines in proteins has hindered their discovery and characterization. Here, a proteomics method to quantitatively profile the intrinsic reactivity of cysteine residues directly in native biological systems is described. Hyper-reactive cysteines were identified in several proteins of uncharacterized function, including a residue conserved across eukaryotes that is shown to be required for yeast viability and involved in iron–sulphur protein biogenesis.

Sichuan is the China’s leading producer of loquat, with the largest cultivation area and yield ranked first in China. Loquat is a seasonal fruit highly appreciated by consumers; however, the fruit is prone to browning and lignification after harvest, affecting its storage quality. The effects of L-Cysteine (L-Cys, 0.01, 0.05, 0.1, 0.2%) and γ-aminobutyric acid (GABA, 0.025, 0.05, 0.075, 0.1%) on the sensory quality and antioxidant activity of loquat fruit during cold storage at 4 °C for 35 days and simulated shelf life for 5 days were investigated. The results showed that after 40 days of storage, compared with the control, 0.05% L-Cys and 0.05% GABA treatment of ‘Zaozhong No. 6’ loquat fruit effectively reduced the weight loss rate, browning index, decay index, respiratory rate, firmness, and lignin content and slowed the decreases in total soluble solids, soluble sugar, titratable acidityand vitamin C contents. The application of 0.05% L-Cys and 0.05% GABA significantly increased the contents of total phenols, total flavonoids, flavanols, and carotenoids; delayed the increase of relative electric conductivity, MDA, POD, and PPO activities; and significantly enhanced the activities of SOD and CAT, DPPH free radical scavenging ability, and FRAP, thereby improving antioxidant capacity. In summary, 0.05% L-Cys and 0.05% GABA treatment promotes the quality of loquat fruit after 40 days of storage, and significantly enhances antioxidant capacity, thus delaying senescence after harvest.

Homocysteine (Hcy) is a biothiol that plays a vital role in many physiological processes and is involved in a variety of diseases. However, it is significantly difficult to discriminate Hcy from cysteine (Cys) due to their similar chemical structures (only one methylene difference) and reactivity. In this study, a novel nanosensor was proposed to discriminate Hcy from Cys with multi-cooperative effects by using gold nanoparticles (AuNPs). The discrimination effect for Hcy originates from the interaction difference of the hydrogen bonding, steric hindrance, and carbon chain length in Hcy and Cys with AuNPs. Under the best conditions, this nanosensor has two unique advantages. Firstly, the sensor exhibits high sensitivity with detection limits of 0.1 μM through naked-eye determination and 0.008 μM through UV−vis spectroscopy analysis. Secondly, the sensor showed superior selectivity for Hcy over the other 16 natural amino acids (biothiol-containing Cys and glutathione (GSH)), and it is the first time to clearly distinguish Hcy from Cys (the Cys concentration is 40 times higher than Hcy). Furthermore, the system was further employed to detect Hcy in human serum, and the result was in agreement with that tested by clinicians via enzymatic assays, with acceptable recovery.

Thirteen popular wild edible mushroom species in Yunnan Province, Boletus bicolor, Boletus speciosus, Boletus sinicus, Boletus craspedius, Boletus griseus, Boletus ornatipes, Xerocomus, Suillus placidus, Boletinus pinetorus, Tricholoma terreum, Tricholomopsis lividipileata, Termitomyces microcarpus, and Amanita hemibapha, were analyzed for their free amino acid compositions by online pre-column derivazation reversed phase high-performance liquid chromatography (RP-HPLC) analysis. Twenty free amino acids, aspartic acid, glutamic acid, serine, glycine, alanine, praline, cysteine, valine, methionine, phenylalanine, isoleucine, leucine, lysine, histidine, threonine, asparagines, glutamine, arginine, tyrosine, and tryptophan, were determined. The total free amino acid (TAA) contents ranged from 1462.6 mg/100 g in B. craspedius to 13,106.2 mg/100 g in T. microcarpus. The different species showed distinct free amino acid profiles. The ratio of total essential amino acids (EAA) to TAA was 0.13–0.41. All of the analyzed species showed high contents of hydrophobic amino acids, at 33%–54% of TAA. Alanine, cysteine, glutamine, and glutamic acid were among the most abundant amino acids present in all species. The results showed that the analyzed mushrooms possessed significant free amino acid contents, which may be important compounds contributing to the typical mushroom taste, nutritional value, and potent antioxidant properties of these wild edible mushrooms. Furthermore, the principal component analysis (PCA) showed that the accumulative variance contribution rate of the first four principal components reached 94.39%. Cluster analysis revealed EAA composition and content might be an important parameter to separate the mushroom species, and T. microcarpus and A. hemibapha showed remarkable EAA content among the 13 species.

Leukotriene receptor antagonists appear to exert anti-inflammatory activity in asthma. We undertook the present study to evaluate the effect of montelukast on levels of exhaled nitric oxide (ENO) and two inflammatory markers, hydrogen peroxide (H2O2), and cysteinyl leukotrienes (cys-LTs), in the exhaled breath condensate of subjects with mild asthma. Twenty stable subjects with mild asthma (15 women and 5 men; mean [± SD] age, 34.8 ± 12.6 years) were included in the study. A 1-week run-in period was followed by 2 weeks of treatment (with montelukast or placebo) that was administered in randomized, double-blind, crossover fashion. One week of washout followed each treatment arm. Montelukast significantly reduced the levels of ENO from baseline (median, 52.5 parts per billion [ppb]; 25th to 75th percentile, 37.8 to 101.8 ppb) during the entire treatment period (ie, day 1 to day 14), with the effect measurable as early as day 1 (median, 45.9 ppb; 25th to 75th percentile, 29.3 to 92.5 ppb) and with the maximal effect being observed on day 7 (median, 35.7 ppb; 25th to 75th percentile, 27.6 to 66.6 ppb). The levels of ENO did not change significantly with placebo therapy. Montelukast improved symptom score and reduced peak expiratory flow (PEF) variability. Changes in PEF variability correlated positively with changes in ENO (r = 0.46; p = 0.04). No significant changes in FEV1 or concentration of H2O2 in the exhaled breath condensate were observed. Levels of cys-LTs were undetectable in the exhaled breath condensate. We concluded that montelukast reduces the levels of ENO in patients with mild asthma, a finding that is compatible with an anti-inflammatory effect of montelukast, and that ENO appears to be more sensitive in detecting this effect than FEV1 and H2O2 levels in the exhaled breath condensate.