Juvenile Plasma Factors Improve Organ Function and Survival following Injury by Promoting Antioxidant Response.

Studies have shown that factors in the blood of young organisms can rejuvenate the old ones. Studies using heterochronic parabiosis models further reinforced the hypothesis that juvenile factors can rejuvenate aged systems. We sought to determine the effect of juvenile plasma-derived factors on the outcome following hemorrhagic shock injury in aged mice. We discovered that pre-pubertal (young) mice subjected to hemorrhagic shock survived for a prolonged period, in the absence of fluid resuscitation, compared to mature or aged mice. To further understand the mechanism of maturational dependence of injury resolution, extracellular vesicles isolated from the plasma of young mice were administered to aged mice subjected to hemorrhagic shock. The extracellular vesicle treatment prolonged life in the aged mice. The treatment resulted in reduced oxidative stress in the liver and in the circulation, along with an enhanced expression of the nuclear factor erythroid factor 2-related factor 2 (Nrf2) and its target genes, and a reduction in the expression of the transcription factor BTB and CNC homology 1 (Bach1). We propose that plasma factors in the juvenile mice have a reparative effect in the aged mice in injury resolution by modulating the Nrf2/Bach1 axis in the antioxidant response pathway.

Regulation of NAD+ metabolism in aging and disease.

More than a century after discovering NAD+, information is still evolving on the role of this molecule in health and diseases. The biological functions of NAD+ and NAD+ precursors encompass pathways in cellular energetics, inflammation, metabolism, and cell survival. Several metabolic and neurological diseases exhibit reduced tissue NAD+ levels. Significantly reduced levels of NAD+ are also associated with aging, and enhancing NAD+ levels improved healthspan and lifespan in animal models. Recent studies suggest a causal link between senescence, age-associated reduction in tissue NAD+ and enzymatic degradation of NAD+. Furthermore, the discovery of transporters and receptors involved in NAD+ precursor (nicotinic acid, or niacin, nicotinamide, and nicotinamide riboside) metabolism allowed for a better understanding of their role in cellular homeostasis including signaling functions that are independent of their functions in redox reactions. We also review studies that demonstrate that the functional effect of niacin is partially due to the activation of its cell surface receptor, GPR109a. Based on the recent progress in understanding the mechanism and function of NAD+ and NAD+ precursors in cell metabolism, new strategies are evolving to exploit these molecules' pharmacological potential in the maintenance of metabolic balance.

Unraveling proteome changes of irradiated goat meat and its relationship to off-flavor analyzed by high-throughput proteomics analysis.

Irradiation has been regarded as a perspective preservation technology to prolong the shelf life of goat meat. In order to evaluate the effect of irradiation on goat meat, the high-throughput proteomics was applied to observe the proteome profiles changes and off-flavor formation of irradiated goat meat. A total of 207 proteins with significant changes (fold change > 2 or < 0.5, P < 0.05, VIP > 1) was determined in five irradiation doses (0, 1, 2, 4 and 6 kGy). Among them, 26 proteins involving 7 functional enrichments terms were found to be related to off-flavor. Particularly, proteins involved in protein oxidation, cysteine and methionine metabolism lead to irradiation off-flavor formation. However, the irradiation off-flavor will gradually dissipate due to metabolic process during storage. This study was designed to provide a proteomic insight into irradiation off-flavor of goat meat and suggest an underlying connection between off-flavor formation and biological processes.

Rapid senescence-like response after acute injury.

Cellular senescence is a state of irreversible growth arrest. Short-term programmed senescence such as in embryonic development and slowly progressing senescence as in aging are both well described. However, acute senescence in living organisms is not well understood. We hypothesized that hemorrhagic shock injury (HI) caused by whole body hypoxia and nutrient deprivation, resulting in organ dysfunction due to severe blood loss, could lead to acute senescence in vivo. Our experiments, for the first time, demonstrate a rapidly emerged, senolytics-responsive, senescence-like response in the rat liver in less than five hr following hemorrhagic shock. We conclude that the senescence, or pseudosenescence, observed is necessary to maintain tissue homeostasis following the injury.

A strategy for the determination of flavor substances in goat milk by liquid chromatography-high resolution mass spectrometry.

A new analytical method for untargeted screening of flavor compounds in goat milk and milk flavor using mass spectrometry was developed and validated. All compounds of low molecular weight were considered as candidate chemicals, instead of focusing only on compounds that already have a known affect on the flavor quality of goat milk. High performance liquid chromatography coupled with high resolution quadrupole orbitrap mass spectrometry based on external standard was used to analyse flavor compounds in complex samples. The untargeted screening strategy is data pre-processing, automated componentization, suspect library spectra searching and the retained analytes confirming based on the reference standard solutions. Forty-two flavor compounds were confirmed and analyzed. The established method was validated by considering the guidelines specified in Commission Decision 2002/657/EC and European SANCO/12571/2013 Guideline 2013. This validated method was successfully applied to samples detection, and some unique flavor compounds were found between goat milk and milk flavor samples, which can provide some useful references for the illicit addition of flavors and fragrances in dairy products.

Discrimination of Milk from Different Animal Species by a Foodomics Approach Based on High-Resolution Mass Spectrometry.

An untargeted foodomics strategy based on ultra-high-performance liquid chromatography coupled with quadrupole orbitrap and chemometrics was used to observe subtle differences in the molecule profiles of raw milk from different animal species (cow milk, goat milk, and water buffalo milk), which could prevent the fraud activities in the dairy industry. In data-dependent acquisition (DIA), spectra for all precursor ions facilitated the comprehensive identification of unknown compounds in untargeted foodomics. Chemometrics techniques were used to analyze large amounts of complex data to observe the separation of different sample groups and find the potential markers of sample groups. Finally, five markers were putatively identified by the potential marker identification workflow. The quantification results showed that ß-carotene was found only in cow milk; ergocalciferol was found only in water buffalo milk; and the contents of nonanoic acid, decanoic acid, and octanoic acid were higher in goat milk than those in cow milk and water buffalo milk. The quantification of ß-carotene enabled the detection of cow milk with a sensitivity threshold of 5% (w/w). This work provided an efficient approach for the discrimination of cow milk, goat milk, and water buffalo milk. Compared with proteomics and genomics, the simpler analytical procedures, lower costs, and higher speed of this work make it of great benefit for routine operations.

Investigation of Differentially Expressed Proteins Induced by Alteration of Natural Se Uptake with Ultrahigh-Performance Liquid Chromatography Quadrupole Orbitrap Uncovers the Potential Nutritional Value in Se-Enriched Green Tea.

Se-enriched green tea, with an increasing consumption, is the shoot of tea plants grown naturally in a seleniferous region. A label-free proteomic strategy based on ultrahigh-performance liquid chromatography quadrupole Orbitrap was applied to characterize and distinguish the difference between the Se-enriched and normal green tea with a total of 283 proteins identified and 264 proteins quantified, in which 96 proteins were observed different. The expressions of 10 proteins were upregulated and 40 proteins were downregulated (p < 0.05) in Se-enriched samples. Gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction (PPI) network analysis results indicated that these differentially expressed proteins significantly interacted and were involved in secondary metabolites and inflammatory response biological processes. Furthermore, the expression of methyl-jasmonate- and ethylene-related genes changed significantly in Se-enriched green tea, and catalase proteins were employed as the center of the pathway that changed significantly in the PPI network. These results associating with the current knowledge of selenium in soil-plant cycling revealed that organic selenium was synthesized in green tea, which provided novel information on Se assimilation in Camellia sinensis and improved the understanding of Se-enriched green tea as a possible ideal selenium supplement in daily life.

Recent advances in Baijiu analysis by chromatography based technology-A review.

Baijiu, a conventional fermented beverage with thousands history, plays a crucial part in physical health of people and social culture in China. The application of high-throughput screening and confirmation of flavor components in the field of authenticity identification and potential function has attracted more and more attention and interest of researchers. With more attention to health, pesticides residues, phthalates, biogenic amines and other hazardous substances remained in Baijiu have also become the quality parameters concerned by consumers. This review aims to present updated and critical overview on the substances analysis of Baijiu by means of hyphenated chromatographic techniques based on various pretreatment approaches in recent years. Subsequently, the advance and main direction of Baijiu composition analysis were evaluated and prospected.

Effects of spices on the formation of biogenic amines during the fermentation of dry fermented mutton sausage.

A precise and unambiguous quantitative strategy for six biogenic amines in dry fermented mutton sausage with liquid chromatography tandem quadrupole Orbitrap mass spectrometry was developed to investigate the inhibitory effects of star anise, amomum tsao-ko, clove, cassia, fennel, bay leaf, and nutmeg on the accumulation of biogenic amines. Compared the data-dependent MS2 fragmentation (dd-MS2), variable data-independent acquisition (vDIA), and multiplex data-independent acquisition (mDIA), and the mDIA acquisition mode was selected for further analysis. The LODs and LOQs were 0.9-1.5 µg kg-1 and 2.9-5.0 µg kg-1. The maximum inhibition of spice on tryptamine, putrescine, spermidine, 2-phenylethylamine, tyrosamine, and histamine were 21.8%, 19.3%, 27.5%, 24.6%, 18.7% and 24.4%, which revealed that the accumulation of BAs was significantly inhibited by spice extracts, while cassia and fennel extracts showed the best effect. Thus, the established method can provide a better reference for dry fermented mutton sausage quality, safety and trade analysis.

Foodomics analysis of natural aging and gamma irradiation maturation in Chinese distilled Baijiu by UPLC-Orbitrap-MS/MS.

Classification of Feng-flavor Baijiu considering aging category was furnished with a comprehensive fingerprinting strategy which used UPLC-Orbitrap and foodomics, and the most discriminant 29 compounds related to aging, 15 organic acids, 8 esters as well as some carbonyl compounds were discovered. Increase of aromatic organic acids, decline of carcinogenic dibutyl phthalate and generation of numerous aromatic substances in Baijiu were caused by irradiation until the system reached a relatively stable state which needed 28 days. It is similarity of physical and chemical reaction process of natural aging and irradiation maturation that both can facilitate flavor of base Baijiu, while the aging time can be plainly shorten utilizing irradiation for Baijiu, whose outcome has been demonstrated by LC-MS and sensory evaluation. The combination of UPLC-Orbitrap and foodomics was applied as a valid tactic to analyze a complex system and gamma irradiation can be a powerful tool to promote Baijiu aging.

A strategy of untargeted foodomics profiling for dynamic changes during Fu brick tea fermentation using ultrahigh-performance liquid chromatography-high resolution mass spectrometry.

During a microbial fermentation process, the chemical composition of Fu brick tea changed substantially. To better profile the unique changes of metabolites and lipids in Fu brick tea at different fermentation stages, a multifaceted strategy combining untargeted foodomics with UHPLC-Q-Orbitrap analysis was developed. The discriminative tea metabolites and lipids were determined by statistical analysis and online database matching. A total of 12 characteristic components (3 metabolic and 9 lipid variables) were found to differ significantly among samples. Quantitative analysis showed that, except for trimyristin and incensole acetate, the content of these compounds gradually increased and finally stabilized with increasing fermentation time. The simultaneous determination of metabolites and lipids in this study provided detailed information for the analysis of multi-component changes in a complex matrix.

NLRX1 Regulation Following Acute Mitochondrial Injury.

Several metabolic, cardiovascular, and neurological disorders are characterized by mitochondrial dysfunction followed by dysregulation of cellular energetics. Mitochondria play an important role in ATP production and cell death regulation. NLRX1, a mitochondria-targeted protein, is known to negatively regulate innate immunity, and cell death responses. However, the role of this protein in cellular homeostasis following mitochondrial injury is not well-understood. To understand the mechanisms underlying the effect of acute injury in regulating NLRX1 signaling pathways, we used an in vitro model of mitochondrial injury wherein, rat pulmonary microvascular endothelial cells were subjected to sodium azide treatment or glucose starvation. Both sodium azide and glucose starvation activated NF-κB and TBK1 associated innate immune response. Moreover, increased TBK1, IKK, IκB, and TRAF6 were recruited to mitochondria and interacted with NLRX1. Depletion of endogenous NLRX1 resulted in exacerbated NF-κB and TBK1 associated innate immune response and apoptosis. Our results suggest that NLRX1 participates in the regulation of innate immune response in mitochondria, and plays an important role in the maintenance of cellular homeostasis following acute mitochondrial injury. We propose that the mitochondrial recruitment of inflammatory mediators and their interaction with NLRX1 are protective responses to maintain cellular homeostasis following injury.

High-throughput mass spectrometry scheme for screening and quantification of flavonoids in antioxidant nutraceuticals.

Antioxidant nutraceuticals functional characteristic science is a challenging field for combining sensitivity and comprehensiveness. A untargeted screening and quantification method based on ultra-high performance liquid chromatography coupled to Quadrupole-Orbitrap high resolution mass spectrometry has been developed for determination of multiple classes of flavonoids in eight-three nutraceuticals samples. The data acquisition is based on a non-target approach of sequential full scan and variable data independent acquisition of twenty consecutive fragmentation events. The flavonoids include flavanols, flavones, flavanones, anthocyanidins, flavonols and isoflavones. A processing strategy is introduced to implementing filtering methods based on data feature extraction, common ion selection, shoulder peak removal, response threshold adjustment, mass shift and characteristic structural fragments evaluation. Confirmation is based on both accurate mass and isotopic assignment of standards, and further quantification is achieved by fragmentation. This scheme allows in depth characterization of flavonoids with the entire fragments.

Accurate determination of volatile-flavor components in bos grunniens milk by high-throughput dynamic headspace gas chromatographic-mass spectrometry.

A dynamic headspace (DHS) with DVB/CAR/PDMS trapping materials was coupled to a gas chromatography-mass spectrometry for the separation and identification of volatile-flavor compounds in bos grunniens (yak) milk. The principal components analysis coupled with response surface methodology optimized the main variables of the device (10 g sample quality, 5 min desorption time, 3.0 g adding sodium chloride, 72 °C extraction temperature, 28 min pre-equilibrium time and 86 min extraction time). Total 235 volatile components were identified. The limit of detections and quantifications of volatile components were 0.01-5.35 mg kg-1 and 0.01-9.41 mg kg-1, respectively, with relative standard deviation from 0.2% to 6.4%. The method performed well during volatile-flavor components analysis from the yak milk sample, producing excellent extraction parameters for the volatile components. Eighty-two volatile components identified in yak milk belonged to a broad range of chemical classes (ketones, aldehydes, aromatics, acids, alkanes, and estes), and 73 of them were at trace levels. Meanwhile, using gas chromatography-olfactometry technique, 11 volatile components were identified as contributors to the aroma of yak milk. In conclusions, a sensitive, convenient and reliable method was developed for the accurate determination of volatile-flavor compounds in yak milk utilizing DHS-GC/MS analyses.

High-throughput screening of the nucleosides and nucleotides using characteristic structural fragments fusion.

Cordyceps sinensis is a traditional Chinese food. A high-throughput screening and quantitative method based on hydrophilic interaction chromatography coupled to quadrupole/Orbitrap high resolution mass spectrometry has been proposed for the joint measurement of nucleosides and their corresponding nucleotides in thirty-two Cordyceps sinensis samples. A total of thirty-two natural samples from six regions were enrolled. A multiple-step analysis strategy, including features extraction, noise level evaluation, mass shift correction and suspect spectral library spectra searching, was employed to discover, identify and validate the nucleosides and nucleotides. The remaining unknown compounds were identified with the characteristic structural fragments. The on-line dispersive solid-phase extraction system eliminates human-based steps errors and affords superior method reproducibility in the presence of hexafluoro-2-propanol and diethylamine as hydrophilic ion-pairing reagents. In view of the great difference of the quality, this high coverage confirmation strategy is of great reference value to the future quantitative analysis of potential nucleosides and nucleotides. Nucleosides and nucleotides ingredients could be considered as origins and quality assessment index of C. sinensis.

Application of the Mechanical High-Pressure Method Combined with High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Determination of Veterinary Drug Residues in Incurred Chicken and Rabbit Muscle Tissues.

Rapid sample preparation is a key step in the field of food safety. A mechanical high-pressure method using a laboratory-made meat press machine was first introduced in this study to process the incurred muscle samples of chicken and rabbit. By applying high pressure to animal muscle, the meat juice was obtained. After extraction and purification, veterinary drug residues in the juice were qualitatively and quantitatively analyzed by using high-performance liquid chromatography-tandem mass spectrometry. The sample press conditions and extraction solvents were optimized. Under the optimal conditions, all veterinary drug residues, including tetracycline, enrofloxacin, clenbuterol, ampicillin, lincomycin, erythromycin, and sulfadiazine, in the incurred samples were detected. The residual concentration of drugs in samples obtained by using the mechanical high-pressure method can reach up to 94.0% of that obtained by using the common homogenization method, suggesting that drug residues exist in the tissue juice, which justifies the use of the mechanical high-pressure method. Moreover, with the mechanical high-pressure method, the sample preparation time was shortened by five times, and the consumption of the extraction solvent was reduced by 50%, relative to the homogenization method.

High-throughput foodomics strategy for screening flavor components in dairy products using multiple mass spectrometry.

A reliable Fisher discriminant model was established which was able to analyze the aroma component in milk, dairy products, flavors and fragrance, and applied on its variety identification. Foodomics was applied on screening of flavor components in 1093 dairy products and flavor samples in this study. Stepwise discrimination was used to screen the components of the dairy products and flavor samples that had a significant effect on the classification results, and discriminant function analysis. Then nine principal components were used for established the Fisher discriminant model. The three-dimensional coordinate distance of the sample was calculated and as the gist. The result showed that samples and flavors were distributed in eight different sites. The separation and clustering effects are better. The objective of the present study was to effectively determine whether or not flavors were added to dairy products.

Deficiency of metabolite sensing receptor HCA2 impairs the salutary effect of niacin in hemorrhagic shock.

Inflammation and cellular energetics play critical roles in organ dysfunction following hemorrhagic shock. Recent studies suggest a putative role for sirtuin 1 (SIRT1) in potentiating mitochondrial function and improving organ function following hemorrhagic shock in animal models. SIRT1 is an NAD+ dependent protein deacetylase and increased availability of NAD+ has been shown to augment SIRT1 activity. As niacin is a precursor of NAD+, in this study, we tested whether niacin can improve survival following hemorrhagic shock. However niacin also mediates its biological action by binding to its receptor, hydroxyl-carboxylic acid receptor 2 (HCA2 or Gpr109a); so we examined whether the effect of niacin is mediated by binding to Gpr109a or by increasing NAD+ availability. We found that niacin administered intravenously to rats subjected to hemorrhagic injury (HI) in the absence of fluid resuscitation resulted in a significantly prolonged duration of survival. However, treatment of rats with similar doses of nicotinamide mononucleotide (NMN), a precursor to NAD+ that does not bind Gpr109a, did not extend survival following HI. The duration of survival due to niacin treatment was significantly reduced in Gpr109a-/- mice subjected to HI. These experiments demonstrated that the Gpr109a receptor-mediated pathway contributed significantly to niacin mediated salutary effect. Further studies showed improvement in markers of cellular energetics and attenuation of inflammatory response with niacin treatment. In conclusion, we report that Gpr109a-dependent signalling is important in restoring cellular energetics and immunometabolism following hemorrhagic shock.

Multiplexing data independent untargeted workflows for mycotoxins screening on a quadrupole-Orbitrap high resolution mass spectrometry platform.

A new multi-analytical strategy was developed to screen mycotoxins and their transformation products in nutraceuticals from green tea. Seven class mycotoxins were determined using a fully automated on-line extraction procedure followed by ultrahigh-performance liquid chromatography coupled to high resolution mass spectrometry. This multi-analytical methodology has been explored providing an entire spectrum of fragment ion peaks for each mycotoxin, which allows unbiased high-throughput screening and quantitation of non-target mycotoxins. The validated mycotoxins exhibited satisfactory recoveries in the range of 82-108% in accordance with 2002/657/EC. The coefficients of linear determination were in the range of 0.9920-0.9999, with relative standard deviations were in the range of 3.2-14.9%. CCß ranged between 0.022 µg kg-1 and 0.50 µg kg-1. The screening and confirmation method was applied to green tea nutraceuticals. Seven samples were found to be positive for mycotoxins at concentrations ranging from 0.23 µg kg-1 (3-acetyldeoxynivalenol) to 7.92 µg kg-1 (T-2 toxin).