Influence of metabolic syndrome on plaque features and clinical outcomes in patients with acute coronary syndrome.

BACKGROUND AND AIMS: Currently, the influence of metabolic syndrome (Mets) on the plaque characteristics and prognosis of patients with acute coronary syndrome (ACS) is poorly understood. Thus, the study aimed to characterize the pancoronay plaques of ACS patients with Mets using optical coherence tomography (OCT) and to evaluate the cohort's prognosis. METHODS: Between February 2015 and September 2020, 745 ACS patients who underwent OCT imaging of the three coronary arteries were included, divided into Mets (n = 252) and non-Mets (n = 493) groups. The major adverse cardiovascular event (MACE) was a composite of cardiac death, non-fatal myocardial infarction (MI), and revascularization. RESULTS: Compared to the non-Mets group, the Mets group exhibited a higher proportion of females and cases of multivessel disease. In the Mets group, culprit lesions were found to have a greater degree of stenosis, thinner fibrous cap thickness and more thin-cap fibroatheroma (TCFA). Additionally, nonculprit lesions were more likely to exhibit plaque rupture, high-risk plaque characteristics, TCFA, macrophage infiltration, cholesterol crystals, and layered plaque. After a median follow-up of 2 years, 8.3% of patients experienced MACE, a rate that was higher in the Mets group, primarily attributed to non-fatal myocardial infarction and cardiac death. Multivariate analysis showed that Mets (aHR 1.73, p = 0.037), high-risk plaque (aHR 2.63, p < 0.001), age (aHR 1.03, p = 0.020), and left ventricular ejection fraction (aHR 0.96, p = 0.002) were independent predictors of MACE. CONCLUSIONS: The presence of Mets increased the vulnerability of the entire coronary tree and worsened the prognosis for patients with ACS.

Dual biomarker traceability and ecological risk assessment of centennial organic contamination in South Dongting Lake.

Enhanced anthropogenic activity strength has altered the watershed particulate transport and material cycle resulting in organic pollutant deposition changes in Dongting Lake associated with unclear ecological risk. In the present study, dual biomarkers i.e. n-alkanes and polycyclic aromatic hydrocarbon (PAHs) were applied in the 210Pb-dated sediment cores for traceability of centennial organic pollutants in the lake mouth area. The partial least squares path model and risk quotients method were used to explore the controlling pathways and ecological risk. The results show a range of sedimentary organic carbon (C), nitrogen (N), and phosphorus (P) was at 1.76-185.66, 0.97-89.80, and 0.01-0.97 g m-2 yr-1 with total reserves of 51.68, 18.44, and 0.27 t ha-1, respectively, over the past 179 years. The presence of PAHs rapidly increased by 2.47 fold from 535.60 ng g-1, while PAHs and carcinogenic PAHs (ΣCPAHs) burial fluxes increased by about 6 and 5 folds, respectively. Accompanied by anthropogenic activities and climate change, the exotic sources gradually becoming predominant. The n-alkane diagnostic ratios indicated a shift of organic matter (OM) from autotrophic bacteria, algae, and phytoplankton-derived sources to macrophyte and terrestrial plants. The exotic origins rose to approximately 73.61 %, while endogenous sources decreased to 26.39 %. The direct effects of anthropogenic activities and their indirect negative impacts on climate and sedimentary structure are the key ways for sediment material loading. The nutrient accumulation in sediments coincides with the lake's eutrophication history over the past decades. The ΣCPAHs accounted for about 89.37 ± 17.14 % of the total TEQ, reflecting a strong ecological risk. The contribution of anthropogenic activities such as fuel usage, fertilizer application, hard pavement coverage, and OM loss from the ecosystem to the sources of organic pollutants and their component types may be a focus of attention in the middle reaches of the Yangtze River plain lake.

The association between iron metabolism with the change of blood pressure and risk of hypertension: A large cross-sectional study.

BACKGROUND: The relationship between iron metabolism and variations in blood pressure and hypertension risk is still not clear. This study aimed to determine whether iron metabolism is associated with changes in blood pressure and hypertension prevalence in the general United States population. METHODS: The National Health and Nutrition Examination Survey (NAHNES) database contains data on 116876 Americans from 1999 to 2020 years. Data from the NHANES database were used to examine the relationships between iron metabolism (serum iron [SI], serum ferritin [SF], and soluble transferrin receptor [sTfR]) and changes in blood pressure and hypertension prevalence. Generalized linear models and restricted cubic spline (RCS) plot curves were used to estimate the relationship between iron metabolism and hypertension. Further, generalized additive models with smooth functions were used to identify the relationship between iron metabolism and blood pressure. Finally, a stratified subgroup analysis was performed. RESULTS: A total of 6710 participants were included in our analysis. The RCS plot showed a linear relationship between SI, as well as sTfR, and hypertension prevalence. SF and hypertension prevalence were associated in a J-shape. In addition, the relationship between SI and systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased initially and then increased. A correlation between SF, SBP, and DBP first decreased, then increased, and finally decreased. A positive linear correlation existed between sTfR and SBP, but it increased and then decreased with DBP. CONCLUSION: The correlation between SF and hypertension prevalence displayed a J-curve. In contrast, the correlation between SI, as well as sTfR, and hypertension risk was negative and positive, respectively.

IDH3γ functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart.

Redox signaling and cardiac function are tightly linked. However, it is largely unknown which protein targets are affected by hydrogen peroxide (H2O2) in cardiomyocytes that underly impaired inotropic effects during oxidative stress. Here, we combine a chemogenetic mouse model (HyPer-DAO mice) and a redox-proteomics approach to identify redox sensitive proteins. Using the HyPer-DAO mice, we demonstrate that increased endogenous production of H2O2 in cardiomyocytes leads to a reversible impairment of cardiac contractility in vivo. Notably, we identify the γ-subunit of the TCA cycle enzyme isocitrate dehydrogenase (IDH)3 as a redox switch, linking its modification to altered mitochondrial metabolism. Using microsecond molecular dynamics simulations and experiments using cysteine-gene-edited cells reveal that IDH3γ Cys148 and 284 are critically involved in the H2O2-dependent regulation of IDH3 activity. Our findings provide an unexpected mechanism by which mitochondrial metabolism can be modulated through redox signaling processes.

Effects of organic carbon burial on biomarker component changes in contamination in northeast Dianchi watershed.

The upper reaches of the Yangtze River have experienced increasing anthropogenic stress. Quantitative tracing of carbon (C) sources and ecological risks through biomarkers i.e., polycyclic aromatic hydrocarbons (PAHs) and n-alkanes is significant for C neutrality and sequestration. Here, source and sink patterns, and factors influencing C burial and biomarker components in a small catchment of Dianchi Lake were explored. The sediment core covered the period 1855-2019. Before 1945, the organic C accumulation rate (OCAR) ranged from 0.71 to 5.12 mg cm-2 yr-1, and the PAHs and n-alkanes fluxes were 106.99-616.09 ng cm-2 yr-1 and 5.56-31.37 µg cm-2 yr-1. During 1945-2005, the OCAR, PAH, and n-alkane burial rapidly increased from 3.19 to 16.17 mg cm-2 yr-1, 230.40 to 2538.81 ng cm-2 yr-1, and 11.63 to 61.90 µg cm-2 yr-1. During 1855-2019, deposition fluxes of PAHs and n-alkanes increased 13.01 and 9.14 times, resulting in increased C burial, driven by environmental changes. A PMF model and the diagnostic ratio indicated that PAHs from coal combustion and traffic emission increased from 22.32% to 65.20% during 1855-2019. The PAH concentrations reflected normal-moderate contamination and potential risks to the aquatic environment. The results facilitate a comprehensive understanding of anthropogenic-driven interactions between increasing OC burial and ecological risks.

Relationship between Novel Anthropometric Indices and the Prevalence of Abdominal Aortic Calcification: A Large Cross-Sectional Study.

Background: The relationship between novel anthropometric indices, specifically a body shape index (ABSI) and body roundness index (BRI), with abdominal aortic calcification (AAC) or severe AAC (SAAC) is unclear. The aim of our study was therefore to investigate possible relationships between novel anthropometric indices and prevalence of AAC and SAAC. Methods: We obtained U.S. general population data from the National Health and Nutrition Examination Survey between 2013 and 2014. The study used restricted cubic spline (RCS) analysis, multivariable logistic regression modeling, subgroup analysis, and receiver operating characteristic (ROC) curve assessment. We investigated relationships between ABSI or BRI and AAC and SAAC risk. Associations between ABSI or BRI and the degree of AAC were also evaluated using a generalized additive model. Results: The study cohort was comprised of 1062 individuals. The RCS plots revealed a U-shaped curve associating ABSI with AAC risk. A similar trend emerged for SAAC, where the risk initially increased before subsequently decreasing with rising ABSI levels. Additionally, BRI exhibited a positive correlation with both AAC and SAAC risk. As ABSI and BRI values increased, the degree of AAC also increased. In ROC analysis, ABSI displayed a significantly larger area under the curve compared to BRI. Conclusions: ABSI is associated with AAC prevalence following a U-shaped curve. Additionally, BRI is positively correlated with AAC risk. ABSI demonstrates a superior discriminative ability for AAC compared to BRI. Therefore, maintaining an appropriate ABSI and BRI may reduce the prevalence of AAC.

[Genetic analysis of a child with Pitt-Hopkins syndrome due to a 18q21.2q21.32 deletion].

OBJECTIVE: To explore the genetic etiology of a child featuring global developmental and mental retardation. METHODS: Chromosome G-banding karyotype analysis, copy number variation sequencing (CNV-seq) and high-resolution chromosome banding were used to screen the genomic variant in the child and his parents. RESULTS: Both the child and his father were found to have a karyotype of 46,XY,del(18)(q21.1q21.3), whilst his mother was 46,XX. CNV-seq analysis showed that the child was arr[19]18q21.2-q21.32(chr18:48 422 190-58 039 582)×1, with a 10.58 Mb deletion which encompassed the TCF4 gene. The same deletion was found in neither parent. High-resolution banding revealed that the father has a fragment of 18q21.1q21.3 inserted into 5p13.1. CONCLUSION: The child was diagnosed with Pitt-Hopkins syndrome due to the 18q21.2q21.32 deletion. Chromosome karyotyping and CNV-seq can effectively identify submicroscopic chromosome anomalies.

Redox regulation of RAD51 Cys319 and homologous recombination by peroxiredoxin 1.

RAD51 is a critical recombinase that functions in concert with auxiliary mediator proteins to direct the homologous recombination (HR) DNA repair pathway. We show that Cys319 RAD51 possesses nucleophilic characteristics and is important for irradiation-induced RAD51 foci formation and resistance to inhibitors of poly (ADP-ribose) polymerase (PARP). We have previously identified that cysteine (Cys) oxidation of proteins can be important for activity and modulated via binding to peroxiredoxin 1 (PRDX1). PRDX1 reduces peroxides and coordinates the signaling actions of protein binding partners. Loss of PRDX1 inhibits irradiation-induced RAD51 foci formation and represses HR DNA repair. PRDX1-deficient human breast cancer cells and mouse embryonic fibroblasts display disrupted RAD51 foci formation and decreased HR, resulting in increased DNA damage and sensitization of cells to irradiation. Following irradiation cells deficient in PRDX1 had increased incorporation of the sulfenylation probe DAz-2 in RAD51 Cys319, a functionally-significant, thiol that PRDX1 is critical for maintaining in a reduced state. Molecular dynamics (MD) simulations of dT-DNA bound to a non-oxidized RAD51 protein showed tight binding throughout the simulation, while dT-DNA dissociated from an oxidized Cys319 RAD51 filament. These novel data establish RAD51 Cys319 as a functionally-significant site for the redox regulation of HR and cellular responses to IR.

Oncogenic KRAS G12C: Kinetic and redox characterization of covalent inhibition.

The recent development of mutant-selective inhibitors for the oncogenic KRASG12C allele has generated considerable excitement. These inhibitors covalently engage the mutant C12 thiol located within the phosphoryl binding loop of RAS, locking the KRASG12C protein in an inactive state. While clinical trials of these inhibitors have been promising, mechanistic questions regarding the reactivity of this thiol remain. Here, we show by NMR and an independent biochemical assay that the pKa of the C12 thiol is depressed (pKa ∼7.6), consistent with susceptibility to chemical ligation. Using a validated fluorescent KRASY137W variant amenable to stopped-flow spectroscopy, we characterized the kinetics of KRASG12C fluorescence changes upon addition of ARS-853 or AMG 510, noting that at low temperatures, ARS-853 addition elicited both a rapid first phase of fluorescence change (attributed to binding, Kd = 36.0 ± 0.7 µM) and a second, slower pH-dependent phase, taken to represent covalent ligation. Consistent with the lower pKa of the C12 thiol, we found that reversible and irreversible oxidation of KRASG12C occurred readily both in vitro and in the cellular environment, preventing the covalent binding of ARS-853. Moreover, we found that oxidation of the KRASG12C Cys12 to a sulfinate altered RAS conformation and dynamics to be more similar to KRASG12D in comparison to the unmodified protein, as assessed by molecular dynamics simulations. Taken together, these findings provide insight for future KRASG12C drug discovery efforts, and identify the occurrence of G12C oxidation with currently unknown biological ramifications.

Redox integration of signaling and metabolism in a head and neck cancer model of radiation resistance using COSMRO.

Redox metabolism is increasingly investigated in cancer as driving regulator of tumor progression, response to therapies and long-term patients' quality of life. Well-established cancer therapies, such as radiotherapy, either directly impact redox metabolism or have redox-dependent mechanisms of action defining their clinical efficacy. However, the ability to integrate redox information across signaling and metabolic networks to facilitate discovery and broader investigation of redox-regulated pathways in cancer remains a key unmet need limiting the advancement of new cancer therapies. To overcome this challenge, we developed a new constraint-based computational method (COSMro) and applied it to a Head and Neck Squamous Cell Cancer (HNSCC) model of radiation resistance. This novel integrative approach identified enhanced capacity for H2S production in radiation resistant cells and extracted a key relationship between intracellular redox state and cholesterol metabolism; experimental validation of this relationship highlights the importance of redox state in cellular metabolism and response to radiation.

Expression of LINE-1 retrotransposon in early human spontaneous abortion tissues.

BACKGROUND: The aim of this study is to investigate a new mechanism that may affect spontaneous abortions (SA): Can long interspersed nuclear element-1 (LINE-1) insertions in embryo cells lead to early SA? METHODS: The method involves prospective study on new mechanism of human early SA. Twenty SA tissues and 10 induced abortion (IA) tissues were utilized for this experiment. Western Blot, Immunohistochemistry (IHC), and reverse transcription-polymerase chain reaction were used to analyze different LINE-1 proteins and mRNA expression between early SA tissues and early IA tissues. SPSS software version 21.0 was used for statistical analysis. RESULTS: Western Blot demonstrated that the LINE-1 protein expression in SA tissues (Mean: 60.2%) is higher than in IA tissues (Mean: 30.3%) in 91% of the compared samples. reverse transcription-polymerase chain reaction showed that LINE-1 mRNA expression in SA tissues (Mean: 64.2%) is higher than in IA tissues (Mean: 29.2%) in 6 primer pairs in 89% of the compared samples. IHC showed that the LINE-1 protein expression in SA tissues (Mean: 59.2%) is higher than in IA tissues (Mean: 28.8%) in 83% of the compared samples. CONCLUSIONS: Expression of LINE-1 in early SA tissues is higher than in IA tissues, LINE-1 may lead to early SA and LINE-1 plays a role in early SA, this shows that a new mechanism may be involved in SA.

Antagonists targeting eEF2 kinase rescue multiple aspects of pathophysiology in Alzheimer's disease model mice.

It is imperative to develop novel therapeutic strategies for Alzheimer's disease (AD) and related dementia syndromes based on solid mechanistic studies. Maintenance of memory and synaptic plasticity relies on de novo protein synthesis, which is partially regulated by phosphorylation of eukaryotic elongation factor 2 (eEF2) via its kinase eEF2K. Abnormally increased eEF2 phosphorylation and impaired mRNA translation have been linked to AD. We recently reported that prenatal genetic suppression of eEF2K is able to prevent aging-related cognitive deficits in AD model mice, suggesting the therapeutic potential of targeting eEF2K/eEF2 signaling in AD. Here, we tested two structurally distinct small-molecule eEF2K inhibitors in two different lines of AD model mice after the onset of cognitive impairments. Our data revealed that treatment with eEF2K inhibitors improved AD-associated synaptic plasticity impairments and cognitive dysfunction, without altering brain amyloid ß (Aß) and tau pathology. Furthermore, eEF2K inhibition alleviated AD-associated defects in dendritic spine morphology, post-synaptic density formation, protein synthesis, and dendritic polyribosome assembly. Our results may offer critical therapeutic implications for AD, and the proof-of-principle study indicates translational implication of inhibiting eEF2K for AD and related dementia syndromes. Cover Image for this issue: https://doi.org/10.1111/jnc.15392.

[18F]Fluoro-DCP, a first generation PET radiotracer for monitoring protein sulfenylation in vivo.

Redox metabolism plays essential functions in the pathology of cancer and many other diseases. While several radiotracers for imaging redox metabolism have been developed, there are no reports of radiotracers for in vivo imaging of protein oxidation. Here we take the first step towards this goal and describe the synthesis and kinetic properties of a new positron emission tomography (PET) [18F]Fluoro-DCP radiotracer for in vivo imaging of protein sulfenylation. Time course biodistribution and PET/CT studies using xenograft animal models of Head and Neck Squamous Cell Cancer (HNSCC) demonstrate its capability to distinguish between tumors with radiation sensitive and resistant phenotypes consistent with previous reports of decreased protein sulfenylation in clinical specimens of radiation resistant HNSCC. We envision further development of this technology to aid research efforts towards improving diagnosis of patients with radiation resistant tumors.

Specificity of Human Sulfiredoxin for Reductant and Peroxiredoxin Oligomeric State.

Human peroxiredoxins (Prx) are a family of antioxidant enzymes involved in a myriad of cellular functions and diseases. During the reaction with peroxides (e.g., H2O2), the typical 2-Cys Prxs change oligomeric structure between higher order (do)decamers and disulfide-linked dimers, with the hyperoxidized inactive state (-SO2H) favoring the multimeric structure of the reduced enzyme. Here, we present a study on the structural requirements for the repair of hyperoxidized 2-Cys Prxs by human sulfiredoxin (Srx) and the relative efficacy of physiological reductants hydrogen sulfide (H2S) and glutathione (GSH) in this reaction. The crystal structure of the toroidal Prx1-Srx complex shows an extended active site interface. The loss of this interface within engineered Prx2 and Prx3 dimers yielded variants more resistant to hyperoxidation and repair by Srx. Finally, we reveal for the first time Prx isoform-dependent use of and potential cooperation between GSH and H2S in supporting Srx activity.

Platelet-derived growth factor receptor beta activates Abl2 via direct binding and phosphorylation.

Abl family kinases are nonreceptor tyrosine kinases activated by diverse cellular stimuli that regulate cytoskeleton organization, morphogenesis, and adhesion. The catalytic activity of Abl family kinases is tightly regulated in cells by a complex set of intramolecular and intermolecular interactions and post-translational modifications. For example, the platelet-derived growth factor receptor beta (PDGFRß), important for cell proliferation and chemotaxis, is a potent activator of Abl family kinases. However, the molecular mechanism by which PDGFRß engages and activates Abl family kinases is not known. We show here that the Abl2 Src homology 2 domain directly binds to phosphotyrosine Y771 in the PDGFRß cytoplasmic domain. PDGFRß directly phosphorylates multiple novel sites on the N-terminal half of Abl2, including Y116, Y139, and Y161 within the Src homology 3 domain, and Y299, Y303, and Y310 on the kinase domain. Y116, Y161, Y272, and Y310 are all located at or near the Src homology 3/Src homology 2-kinase linker interface, which helps maintain Abl family kinases in an autoinhibited conformation. We also found that PDGFRß-mediated phosphorylation of Abl2 in vitro activates Abl2 kinase activity, but mutation of these four tyrosines (Y116, Y161, Y272, and Y310) to phenylalanine abrogated PDGFRß-mediated activation of Abl2. These findings reveal how PDGFRß engages and phosphorylates Abl2 leading to activation of the kinase, providing a framework to understand how growth factor receptors engage and activate Abl family kinases.

Integrated Redox Proteomic Analysis Highlights New Mechanisms of Sensitivity to Silver Nanoparticles.

Silver nanoparticles (AgNPs) are widely used nanomaterials in both commercial and clinical biomedical applications, but the molecular mechanisms underlying their activity remain elusive. In this study we profiled proteomics and redox proteomics changes induced by AgNPs in two lung cancer cell lines: AgNPs-sensitive Calu-1 and AgNPs-resistant NCI-H358. We show that AgNPs induce changes in protein abundance and reversible oxidation in a time and cell-line-dependent manner impacting critical cellular processes such as protein translation and modification, lipid metabolism, bioenergetics, and mitochondrial dynamics. Supporting confocal microscopy and transmission electron microscopy (TEM) data further emphasize mitochondria as a target of AgNPs toxicity differentially impacting mitochondrial networks and morphology in Calu-1 and NCI-H358 lung cells. Proteomics data are available via ProteomeXchange with identifier PXD021493.

Identification of sulfenylation patterns in trophozoite stage Plasmodium falciparum using a non-dimedone based probe.

Plasmodium falciparum causes the deadliest form of malaria. Adequate redox control is crucial for this protozoan parasite to overcome oxidative and nitrosative challenges, thus enabling its survival. Sulfenylation is an oxidative post-translational modification, which acts as a molecular on/off switch, regulating protein activity. To obtain a better understanding of which proteins are redox regulated in malaria parasites, we established an optimized affinity capture protocol coupled with mass spectrometry analysis for identification of in vivo sulfenylated proteins. The non-dimedone based probe BCN-Bio1 shows reaction rates over 100-times that of commonly used dimedone-based probes, allowing for a rapid trapping of sulfenylated proteins. Mass spectrometry analysis of BCN-Bio1 labeled proteins revealed the first insight into the Plasmodium falciparum trophozoite sulfenylome, identifying 102 proteins containing 152 sulfenylation sites. Comparison with Plasmodium proteins modified by S-glutathionylation and S-nitrosation showed a high overlap, suggesting a common core of proteins undergoing redox regulation by multiple mechanisms. Furthermore, parasite proteins which were identified as targets for sulfenylation were also identified as being sulfenylated in other organisms, especially proteins of the glycolytic cycle. This study suggests that a number of Plasmodium proteins are subject to redox regulation and it provides a basis for further investigations into the exact structural and biochemical basis of regulation, and a deeper understanding of cross-talk between post-translational modifications.

Discovery of Spilanthol Endoperoxide as a Redox Natural Compound Active against Mammalian Prx3 and Chlamydia trachomatis Infection.

Chlamydia trachomatis (Ct) is a bacterial intracellular pathogen responsible for a plethora of diseases ranging from blindness to pelvic inflammatory diseases and cervical cancer. Although this disease is effectively treated with antibiotics, concerns for development of resistance prompt the need for new low-cost treatments. Here we report the activity of spilanthol (SPL), a natural compound with demonstrated anti-inflammatory properties, against Ct infections. Using chemical probes selective for imaging mitochondrial protein sulfenylation and complementary assays, we identify an increase in mitochondrial oxidative state by SPL as the underlying mechanism leading to disruption of host cell F-actin cytoskeletal organization and inhibition of chlamydial infection. The peroxidation product of SPL (SPL endoperoxide, SPLE), envisioned to be the active compound in the cellular milieu, was chemically synthesized and showed more potent anti-chlamydial activity. Comparison of SPL and SPLE reactivity with mammalian peroxiredoxins, demonstrated preferred reactivity of SPLE with Prx3, and virtual lack of SPL reaction with any of the reduced Prx isoforms investigated. Cumulatively, these findings support the function of SPL as a pro-drug, which is converted to SPLE in the cellular milieu leading to inhibition of Prx3, increased mitochondrial oxidation and disruption of F-actin network, and inhibition of Ct infection.

Use of Metabolomic Profiling to Understand Variability in Adiposity Changes Following an Intentional Weight Loss Intervention in Older Adults.

Inter-individual response to dietary interventions remains a major challenge to successful weight loss among older adults. This study applied metabolomics technology to identify small molecule signatures associated with a loss of fat mass and overall weight in a cohort of older adults on a nutritionally complete, high-protein diet. A total of 102 unique metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) for 38 adults aged 65-80 years randomized to dietary intervention and 36 controls. Metabolite values were analyzed in both baseline plasma samples and samples collected following the six-month dietary intervention to consider both metabolites that could predict the response to diet and those that changed in response to diet or weight loss.Eight metabolites changed over the intervention at a nominally significant level: D-pantothenic acid, L-methionine, nicotinate, aniline, melatonin, deoxycarnitine, 6-deoxy-L-galactose, and 10-hydroxydecanoate. Within the intervention group, there was broad variation in the achieved weight-loss and dual-energy x-ray absorptiometry (DXA)-defined changes in total fat and visceral adipose tissue (VAT) mass. Change in the VAT mass was significantly associated with the baseline abundance of α-aminoadipate (p = 0.0007) and an additional mass spectrometry peak that may represent D-fructose, myo-inositol, mannose, α-D-glucose, allose, D-galactose, D-tagatose, or L-sorbose (p = 0.0001). This hypothesis-generating study reflects the potential of metabolomic biomarkers for the development of personalized dietary interventions.

Mass Spectrometry in Advancement of Redox Precision Medicine.

Redox (portmanteau of reduction-oxidation) reactions involve the transfer of electrons between chemical species in biological processes fundamental to life. It is of outmost importance that cells maintain a healthy redox state by balancing the action of oxidants and antioxidants; failure to do so leads to a multitude of diseases including cancer, diabetes, fibrosis, autoimmune diseases, and cardiovascular and neurodegenerative diseases. From the perspective of precision medicine, it is therefore beneficial to interrogate the redox phenotype of the individual-similar to the use of genomic sequencing-in order to design tailored strategies for disease prevention and treatment. This chapter provides an overview of redox metabolism and focuses on how mass spectrometry (MS) can be applied to advance our knowledge in redox biology and precision medicine.