Epidemiological characterization and risk factors of rhinitis and rhinoconjunctivitis among preschool children in Shanghai, China.

BACKGROUND: Previous studies have reported an increasing prevalence of childhood allergic rhinitis in developing countries. There is still a lack of the recent epidemiology of allergic rhinitis among Chinese preschool children. Therefore, this study explored the prevalence of rhinitis symptoms and identified their associations with potential risk factors among children at the age of 3-6 in Shanghai, China. METHODS: Validated International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was adopted to collect information about rhinitis symptoms and potential risk factors. Univariate and multivariate logistic regression analyses were used to assess associations between risk factors and allergic rhinitis and rhinoconjunctivitis. RESULTS: A total of 6183 questionnaires were included in our study. The prevalence of rhinitis ever, current rhinitis, and physician-diagnosed rhinitis were 32.6%, 29.2%, and 14.3%, respectively, while the prevalence of current rhinoconjunctivitis was 11.3%. The higher prevalence was observed in boys than in girls in terms of rhinitis ever, current rhinitis, current rhinoconjunctivitis and doctor-diagnosed rhinitis. Autumn had the highest prevalence among four seasons. In our multivariate logistic regression analyses, history of allergic diseases and paracetamol use in the last year showed positive associations with the increased risk of both current rhinitis and rhinoconjunctivitis, and antibiotic use was an independent significant risk factor only for current rhinitis. Genetic factors, including maternal and paternal rhinitis, asthma, and eczema, were significantly associated with the prevalence of current rhinitis. Similar associations were seen between these factors and current rhinoconjunctivitis, except for paternal eczema. Among environmental factors, smoking exposure at home, heavy truck traffic in home's street, floor heating system were independent risk factors for both current rhinitis and rhinoconjunctivitis in the adjusted model, while cleaning the house less than once a week was only associated with current rhinitis. CONCLUSION: The prevalence of current rhinitis was 29.2% among children aged 3-6 in Shanghai, China. Sex differences and seasonal variations were observed in the prevalence of rhinitis symptoms. The identified risk factors would provide a basis for policy makers and medical experts to take intervention measures to prevent allergic rhinitis and rhinoconjunctivitis.

Immobilized lipase for sustainable hydrolysis of acidified oil to produce fatty acid.

Acidified oil is obtained from by-product of crops oil refining industry, which is considered as a low-cost material for fatty acid production. Hydrolysis of acidified oil by lipase catalysis for producing fatty acid is a sustainable and efficient bioprocess that is an alternative of continuous countercurrent hydrolysis. In this study, lipase from Candida rugosa (CRL) was immobilized on magnetic Fe3O4@SiO2 via covalent binding strategy for highly efficient hydrolysis of acidified soybean oil. FTIR, XRD, SEM and VSM were used to characterize the immobilized lipase (Fe3O4@SiO2-CRL). The enzyme properties of the Fe3O4@SiO2-CRL were determined. Fe3O4@SiO2-CRL was used to catalyze the hydrolysis of acidified soybean oil to produce fatty acids. Catalytic reaction conditions were studied, including amount of catalyst, reaction time, and water/oil ratio. The results of optimization indicated that the hydrolysis rate reached 98% under 10 wt.% (oil) of catalyst, 3:1 (v/v) of water/oil ratio, and 313 K after 12 h. After 5 cycles, the hydrolysis activity of Fe3O4@SiO2-CRL remained 55%. Preparation of fatty acids from high-acid-value by-products through biosystem shows great industrial potential.

Effect of Glutaraldehyde Multipoint Covalent Treatments on Immobilized Lipase for Hydrolysis of Acidified Oil.

Immobilized lipase is a green and sustainable catalyst for hydrolysis of acidified oil. Glutaraldehyde is widely used for lipase immobilization while the appropriate strategy optimizes the catalytic performance of lipase. In this research, lipase from Candida rugosa (CRL) was immobilized on spherical silica (SiO2) by glutaraldehyde multipoint covalent treatments, including covalent binding method and adsorption-crosslinking method. The enzymatic stability properties and performance in hydrolysis of refined oil and acidified oil were studied. We confirmed that the residual activity decreased while the stability increased because of the influence on secondary structure of lipase after multipoint covalent treatments. In the comparison of different immobilization strategies in multipoint covalent treatment, SiO2-CRL (covalent binding method) showed lower loading capacity than SiO2-CRL (adsorption-crosslinking method), resulting in low activity. However, SiO2-CRL (covalent binding method) showed better reusability and stability. Immobilized lipase via covalent binding method was more potential in the application of catalytic hydrolysis of acidified oils.

Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry.

BACKGROUND: Identifying T cell epitopes on pancreatic ductal adenocarcinoma (PDAC) associated antigens or neoantigens has been a challenge. In this study, we attempted to identify PDAC T cell epitopes by mass spectrometry (MS). METHODS: We isolated HLA class I (HLA-I) and HLA class II (HLA-II)-restricted peptides, respectively, from tissues of human PDAC by using the pan-HLA-I or pan-HLA-II affinity purification column and identified T cell epitopes by peptidome analysis with MS. RESULTS: Through peptidome analysis, we identified T cell epitopes shared by multiple patients with different HLA types and those containing sequences of both anti-HLA-I and HLA-II antibodies-affinity purified peptides. The identified epitopes bound non-matched HLA molecules and induced T cell response in peripheral T cells from both HLA-type matched and non-matched patients. Peptides containing both HLA class I and class II epitopes were able to induce polyfunctional cytokine responses in peripheral T cells. CONCLUSIONS: T cell epitopes in PDAC can be discovered by the MS approach and can be designed into vaccine and TCR-T cell therapies for both HLA-type matched and non-matched patients.

High specific surface CeO2-NPs doped loose porous C3N4for enhanced photocatalytic oxidation ability.

Porous C3N4(PCN) is favored by researchers because it has more surface active sites, higher specific surface area and stronger light absorption ability than traditional g-C3N4. In this study, cerium dioxide nanoparticles (CeO2-NPs) with mixed valence state of Ce3+and Ce4+were doped into the PCN framework by a two-step method. The results indicate that CeO2-NPs are highly dispersed in the PCN framework, which leads to a narrower band gap, a wider range of the light response and an improved the separation efficiency of photogenerated charge in PCN. Moreover, the specific surface area (145.69 m2g-1) of CeO2-NPs doped PCN is a 25.5% enhancement than that of PCN (116.13 m2g-1). In the experiment of photocatalytic selective oxidation of benzyl alcohol, CeO2-NPs doped porous C3N4exhibits excellent photocatalytic activity, especially Ce-PCN-30. The conversion rate of benzyl alcohol reaches 74.9% using Ce-PCN-30 as photocatalyst by 8 h of illumination, which is 25.7% higher than that of pure porous C3N4. Additionally, CeO2-NPs doped porous C3N4also exhibits better photocatalytic efficiency for other aromatic alcohols.

Novel Human Insulin Isoforms and Cα-Peptide Product in Islets of Langerhans and Choroid Plexus.

Human insulin (INS) gene diverged from the ancestral genes of invertebrate and mammalian species millions of years ago. We previously found that mouse insulin gene (Ins2) isoforms are expressed in brain choroid plexus (ChP) epithelium cells, where insulin secretion is regulated by serotonin and not by glucose. We further compared human INS isoform expression in postmortem ChP and islets of Langerhans. We uncovered novel INS upstream open reading frame isoforms and their protein products. In addition, we found a novel alternatively spliced isoform that translates to a 74-amino acid (AA) proinsulin containing a shorter 19-AA C-peptide sequence, herein designated Cα-peptide. The middle portion of the conventional C-peptide contains ß-sheet (GQVEL) and hairpin (GGGPG) motifs that are not present in Cα-peptide. Islet amyloid polypeptide (IAPP) is not expressed in ChP, and its amyloid formation was inhibited in vitro more efficiently by Cα-peptide than by C-peptide. Of clinical relevance, the ratio of the 74-AA proinsulin to proconvertase-processed Cα-peptide was significantly increased in islets from type 2 diabetes mellitus autopsy donors. Intriguingly, 100 years after the discovery of insulin, we found that INS isoforms are present in ChP from insulin-deficient autopsy donors.

Primary angle closure glaucoma is characterized by altered extracellular matrix homeostasis in the iris.

PURPOSE: To characterize the proteome of the iris in primary angle closure glaucoma (PACG). EXPERIMENTAL DESIGN: In this cross-sectional study, iris samples were obtained from surgical iridectomy of 48 adults with PACG and five normal controls. Peptides from iris were analysed using liquid chromatography-tandem mass spectrometry on an Orbitrap Q Exactive Plus mass spectrometer. Verification of proteins of interest was conducted using selected reaction monitoring on a triple quadrupole mass spectrometer. The main outcome was proteins with a log2 two-fold difference in expression in iris between PACG and controls. RESULTS: There were 3,446 non-redundant proteins identified in human iris, of which 416 proteins were upregulated and 251 proteins were downregulated in PACG compared with controls. Thirty-two upregulated proteins were either components of the extracellular matrix (ECM) (fibrillar collagens, EMILIN-2, fibrinogen, fibronectin, matrilin-2), matricellular proteins (thrombospondin-1), proteins involved in cell-matrix interactions (integrins, laminin, histidine-rich glycoprotein, paxillin), or protease inhibitors known to modulate ECM turnover (α-2 macroglobulin, tissue factor pathway inhibitor 2, papilin). Two giant proteins, titin and obscurin, were up- and down-regulated, respectively, in the iris in PACG compared with controls. CONCLUSIONS AND CLINICAL RELEVANCE: This proteomic study shows that ECM composition and homeostasis are altered in the iris in PACG.

Prevalence and Risk Factors of Asthma in Preschool Children in Shanghai, China: A Cross-Sectional Study.

BACKGROUND: Previous studies have shown the increasing prevalence of childhood asthma around the world as well as in China. Nevertheless, little is known about the epidemiology of asthma in preschool children. Thus, the present study investigated the prevalence and severity of asthma in Shanghai, China, and identified related risk factors for asthma in children at the age of 3-6. METHODS: Information was obtained through the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Risk factor analysis was carried out using univariate and multivariate logistic regression. The odds ratio (OR)/adjusted odds ratio (aOR) and the 95% confidence interval (CI) were determined. RESULTS: A total of 6,183 children (3,165 boys and 3,018 girls) covering 12 communities were included in our study, with an average age of 4.2 ± 0.7 years. The prevalence of ever asthma, current asthma, and physician-diagnosed asthma was 16.0, 11.2, and 5.3%, respectively. Parental allergic history, including rhinitis and asthma, was significantly associated with asthma symptoms. The strongest association with current asthma was paternal asthma (aOR = 5.91, 95% CI 3.87-9.01), and maternal asthma had the second strongest association with current asthma (3.85; 2.40-6.17). Among personal factors, allergic rhinitis history, eczema history, food allergy history, and antibiotic use in the first year of life were significantly associated with current asthma (aOR = 1.89, 95% CI 1.52-2.34; aOR = 1.34, 95% CI 1.09-1.64; aOR = 1.68, 95% CI 1.37-2.06; aOR = 1.53, 95% CI 1.25-1.87, respectively). More than once paracetamol use per year and per month were associated with current asthma in a dose-response manner. Additionally, female sex was an independent protective factor for ever asthma (0.82; 0.70-0.96). Among environmental factors, dampness or mildew at home was an independent risk factor for ever asthma (1.50; 1.15-1.97) and current asthma (1.63; 1.21-2.19). Floor heating system was significantly associated with ever asthma (1.57; 1.25-1.98) and current asthma (1.36; 1.04-1.78). Furthermore, dampness or mildew, infrequent house cleaning, and truck traffic in residential streets were significantly associated with asthma symptoms only in old communities, while paracetamol use in the first year of life and flooring materials were significant factors only in new communities. CONCLUSION: The prevalence of asthma has increased among preschool children in Shanghai over the past three decades. The identified risk factors indicated the combined effects of genetic, personal, and environmental factors on asthma symptoms. Differentiated strategies should be taken for preventing asthma in old and new communities.

Elevated Plasma Growth and Differentiation Factor 15 Is Associated With Slower Gait Speed and Lower Physical Performance in Healthy Community-Dwelling Adults.

BACKGROUND: Growth and differentiation factor 15 (GDF-15) has been associated with obesity, muscle wasting, and cachexia. The receptor for GDF-15 was recently identified in the brainstem and regulates food intake and metabolism. The relationship of plasma GDF-15 with the age-associated decline of muscle mass and strength, gait speed, and physical performance in adults has not been well characterized. METHODS: Plasma GDF-15, grip strength, 6-m gait speed, 400-m walking test time, lower extremity physical performance score, appendicular lean mass, and fat mass were measured in 194 healthy adult participants, aged 22-93 years, of the Baltimore Longitudinal Study of Aging. RESULTS: Plasma GDF-15 concentrations increased with age (p < .001) and were higher in whites compared with blacks and Asians (p = .04). Adults with higher plasma GDF-15 had slower 6-m gait speed, longer 400-m walking time, and lower physical performance score in multivariable analyses adjusting for age and race. Plasma GDF-15 was not associated with grip strength, appendicular lean mass, or fat mass. CONCLUSIONS: Elevated plasma GDF-15 is associated with slower gait speed, higher 400-m walking time, and lower physical performance in very healthy community-dwelling adults. The relationship between plasma GDF-15 and sarcopenia-related outcomes may be stronger in the population not selected to be healthy, and this hypothesis should be tested in a representative population.

Tetra-linoleoyl cardiolipin depletion plays a major role in the pathogenesis of sarcopenia.

Sarcopenia, the progressive loss of muscle mass, strength, and physical performance that occurs during aging, is highly prevalent among the elderly. Sarcopenia increases the risk of falls, disability, and death. The biological basis for sarcopenia is not well understood. There are no specific preventive or therapeutic strategies for sarcopenia except exercise. The elucidation of biological pathways and identification of therapeutic targets for treating or preventing sarcopenia remain a high priority in aging research. Mitochondria play a critical role in skeletal muscle by providing energy in the form of ATP, regulation of signaling, calcium homeostasis, autophagy, and other functions. Cardiolipin, a unique dimeric phospholipid specific to mitochondria and an essential component of mitochondrial membranes, is involved in mitochondrial protein transport, maintaining structural organization of mitochondrial membranes, cellular signaling, regulating enzymes involved in ß-oxidation of fatty acids, and facilitating normal electron transport chain (ETC) function and generation of ATP. The fatty acid species composition of cardiolipin is critical to mitochondrial bioenergetics, as cardiolipin affects membrane biophysical properties, binds and stabilizes ETC protein complexes, and shapes the curvature of the mitochondrial cristae. Tetra-linoleoyl cardiolipin (18:2)4 comprises ∼80% of cardiolipin in mitochondria in normal human skeletal and cardiac muscle and is optimal for effective ETC function and ATP generation. Aging is associated with a decrease in cardiolipin content, decrease in tetra-linoleoyl cardiolipin (18:2)4 and replacement of linoleic acid (18:2) with other fatty acids in cardiolipin composition, decline of ETC function, and increased generation of reactive oxygen species in muscle. Together, these findings from the literature prompt the hypothesis that depletion of the cardiolipin (18:2)4 species may be at the root of mitochondrial dysfunction with aging, in turn leading to sarcopenia. Corroboration of the tetra-linoleoyl cardiolipin depletion hypothesis suggests new leads for the prevention and treatment of sarcopenia by enhancing the biosynthesis, accretion, and integrity of tetra-linoleoyl cardiolipin.

Low plasma lysophosphatidylcholines are associated with impaired mitochondrial oxidative capacity in adults in the Baltimore Longitudinal Study of Aging.

The decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects muscle strength and physical performance. Factors that are associated with this decrease have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, are predictive of aging phenotypes such as cognitive impairment and decline of gait speed in older adults. Therefore, we tested the hypothesis that low plasma LPC are associated with impaired skeletal muscle mitochondrial oxidative capacity. Skeletal muscle mitochondrial oxidative capacity was measured using in vivo phosphorus magnetic resonance spectroscopy (31 P-MRS) in 385 participants (256 women, 129 men), aged 24-97 years (mean 72.5) in the Baltimore Longitudinal Study of Aging. Postexercise recovery rate of phosphocreatine (PCr), kPCr , was used as a biomarker of mitochondrial oxidative capacity. Plasma LPC were measured using liquid chromatography-tandem mass spectrometry. Adults in the highest quartile of kPCr had higher plasma LPC 16:0 (p = 0.04), 16:1 (p = 0.004), 17:0 (p = 0.01), 18:1 (p = 0.0002), 18:2 (p = 0.002), and 20:3 (p = 0.0007), but not 18:0 (p = 0.07), 20:4 (p = 0.09) compared with those in the lower three quartiles in multivariable linear regression models adjusting for age, sex, and height. Multiple machine-learning algorithms showed an area under the receiver operating characteristic curve of 0.638 (95% confidence interval, 0.554, 0.723) comparing six LPC in adults in the lower three quartiles of kPCr with the highest quartile. Low plasma LPC are associated with impaired mitochondrial oxidative capacity in adults.

Targeted Metabolomics Shows Low Plasma Lysophosphatidylcholine 18:2 Predicts Greater Decline of Gait Speed in Older Adults: The Baltimore Longitudinal Study of Aging.

Background: Gait speed is an important measure of lower extremity physical performance in older adults and is predictive of disability and mortality. The biological pathways involved in the decline of lower extremity physical performance are not well understood. We used a targeted metabolomics approach to identify plasma metabolites predictive of change in gait speed over time. Methods: Gait speed was measured at baseline and over median follow-up of 50.5 months in 504 adults, aged ≥50 years, who had two or more study visits in the Baltimore Longitudinal Study of Aging (BLSA). Plasma metabolites were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates). Results: Of 148 plasma metabolites (amino acids, biogenic amines, hexoses, glycerophospholipids) measured, eight were significantly associated with gait speed at baseline, independent of age and sex: hexoses (r = -0.148, p < .001), [sphingomyelin (SM) 16:1 (r = -0.091, p = .0009), SM 18:0 (r = -0.085, p = .002), SM 18:1 (r = -0.128, p < .0001], phosphatidylcholine aa 32:3 (r = -0.088, p = .001), lysophosphatidylcholine (LPC) 17:0 (r = 0.083, p = .003), LPC 18:1 (r = 0.089, p = .001), and LPC 18:2 (r = 0.104, p < .0001). Adjusting for baseline age, sex, and chronic diseases, baseline plasma LPC 18:2 was an independent predictor of the rate of change of gait speed over subsequent follow-up (p = .003). No other plasma metabolites were significantly associated longitudinal changes of gait speed over time. Conclusions: Low plasma LPC 18:2, which has previously been shown to predict impaired glucose tolerance, insulin resistance, type 2 diabetes, coronary artery disease, and memory impairment, is an independent predictor of decline in gait speed in older adults.

Relationship of Circulating Growth and Differentiation Factors 8 and 11 and Their Antagonists as Measured Using Liquid Chromatography-Tandem Mass Spectrometry With Age and Skeletal Muscle Strength in Healthy Adults.

Background: Growth and differentiation factors 8 (GDF8) and 11 (GDF11) have attracted attention as targets for rejuvenating interventions. The biological activity of these proteins may be affected by circulating antagonists such as their respective prodomains, follistatin (FST315), WFIKKN1, and WFIKKN2. Reports of the relationship of GDF8 and GDF11 and their antagonists with aging and aging phenotypes such as skeletal muscle strength have been conflicting possibly because of difficulties in measuring these proteins and polypeptides. Methods: Plasma GDF8 and GDF11 and their antagonists were measured using a multiplexed selected reaction monitoring assay and liquid chromatography-tandem mass spectrometry in 160 healthy adults aged 22-93 years. Quadriceps strength was measured by knee extensor torque using isokinetic dynamometry. Results: Spearman correlations with age were the following: GDF11 prodomain (r = .30, p = .001), GDF11 mature protein (r = .23, p = .004), FST315 (r = .32, p < .0001), WFIKKN1 (r = -.21, p = 0.008), and WFIKKN2 (r = .18, p = .02). Independent of age, FST315 and WFIKKN1 were negatively associated with knee strength (p = .02, p = .03, respectively) in a multivariable model that included both GDF8 and GDF11 mature proteins. Conclusions: When measured by an antibody-free selected reaction monitoring assay, GDF8, GDF11, and their antagonists are found in the circulation in the ng/mL range. In healthy adults, plasma GDF11 and antagonists FST315, WFIKKN1, and WFIKKN2 differed by age. Antagonists of GDF8 and GDF11, but not GDF8 and GDF11, were independently associated with skeletal muscle strength. Further work is needed to characterize the relationship of these protein and polypeptides with sarcopenia-related phenotypes such as physical function and walking disability.

Catalytic developments in the epoxidation of vegetable oils and the analysis methods of epoxidized products.

Functionalization of vegetable oils (VOs) including edible, non-edible, and waste cooking oil (WCOs) to epoxides (EVOs) is receiving great attention by many researchers from academia and industry because they are renewable, versatile, sustainable, non-toxic, and eco-friendly, and they can partially or totally replace harmful phthalate plasticizers. The epoxidation of VOs on an industrial scale has already been developed by the homogeneous catalytic system using peracids. Due to the drawbacks of this method, other systems including acidic ion exchange resins, polyoxometalates, and enzymes are becoming alternative catalysts for the epoxidation reaction. We have reviewed all these catalytic systems including their benefits and drawbacks, reaction mechanisms, intensification of each system in different ways as well as the physicochemical properties of VOs and EVOs and new findings in recent years. Finally, the current methods including titrimetric methods as well as ATR-FTIR and 1H NMR for determination of conversion, epoxidation, and selectivity of epoxidized vegetable oils (EVOs) are also briefly described.

Plasma proteomic signature of age in healthy humans.

To characterize the proteomic signature of chronological age, 1,301 proteins were measured in plasma using the SOMAscan assay (SomaLogic, Boulder, CO, USA) in a population of 240 healthy men and women, 22-93 years old, who were disease- and treatment-free and had no physical and cognitive impairment. Using a p ≤ 3.83 × 10-5 significance threshold, 197 proteins were positively associated, and 20 proteins were negatively associated with age. Growth differentiation factor 15 (GDF15) had the strongest, positive association with age (GDF15; 0.018 ± 0.001, p = 7.49 × 10-56 ). In our sample, GDF15 was not associated with other cardiovascular risk factors such as cholesterol or inflammatory markers. The functional pathways enriched in the 217 age-associated proteins included blood coagulation, chemokine and inflammatory pathways, axon guidance, peptidase activity, and apoptosis. Using elastic net regression models, we created a proteomic signature of age based on relative concentrations of 76 proteins that highly correlated with chronological age (r = 0.94). The generalizability of our findings needs replication in an independent cohort.

Altered Plasma Amino Acids and Lipids Associated With Abnormal Glucose Metabolism and Insulin Resistance in Older Adults.

Context and Objectives: Glucose metabolism becomes progressively impaired with older age. Fasting glucose and insulin resistance are risk factors for premature death and other adverse outcomes. We aimed to identifying plasma metabolites associated with altered glucose metabolism and insulin resistance in older community-dwelling adults. Participants and Methods: A targeted metabolomics approach was used to identify plasma metabolites associated with impaired fasting plasma glucose, 2-hour plasma glucose on oral glucose tolerance testing, and homeostatic model assessment insulin resistance (HOMA-IR) in 472 participants who participated in the Baltimore Longitudinal Study of Aging, with a mean (SD) age of 70.7 (9.9) years. Results: We measured 143 plasma metabolites. In ordinal logistic regression analyses, using a false discovery rate of 5% and adjusting for potential confounders, we found that alanine, glutamic acid, and proline were significantly associated with increased odds of abnormal fasting plasma glucose. Phosphatidylcholine (diacyl C34:4, alkyl-acyl C32:1, C32:2, C34:2, C34:3, and C36:3) was associated with decreased odds of abnormal fasting plasma glucose. Glutamic and acid phosphatidylcholine alkyl-acyl C34:2 were associated with increased and decreased odds of 2-hour plasma glucose, respectively. Glutamic acid was associated with increased odds of higher tertiles of HOMA-IR. Glycine; phosphatidylcholine (diacyl C32:0, alkyl-acyl C32:1, C32:2, C34:1, C34:2, C34:3, C36:2, C36:3, C40:5, C40:6, C42:3, C42:4, and C42:5); sphingomyelin C16:0, C24:1, and C26:1; and lysophosphatidylcholine C18:1 were associated with decreased odds of abnormal HOMA-IR. Conclusions: Targeted metabolomics identified four plasma amino acids and 16 plasma lipid species, primarily containing polyunsaturated fatty acids, that were associated with abnormal glucose metabolism and insulin resistance in older adults.

The Human Eye Proteome Project: Updates on an Emerging Proteome.

The human eye is a complex organ consisting of multiple compartments with unique and specialized properties that reflect their varied functions. Although there have been advancements in ocular imaging and therapeutics over the past decade, the pathogenesis of many common eye diseases remains poorly understood. Proteomics is an invaluable tool to gain insight into pathogenesis, diagnosis, and treatment of eye diseases. By 2013, when the Human Eye Proteome Project (also known as the EyeOme) was founded, there were 4842 nonredundant proteins identified in the human eye. Twenty-three recent papers on the human eye proteome were identified in PubMed searches. These papers were used to compile an updated resource of 9782 nonredundant proteins in the human eye. This updated catalogue sheds light on the molecular makeup of previously undescribed proteomes within the human eye, including optic nerve, sclera, iris, and ciliary body, while adding additional proteins to previously characterized proteomes such as aqueous humor, lens, vitreous, retina, and retinal pigment epithelium/choroid. Although considerable advances have been made to characterize the complete proteome of the human eye, additional high-quality data are needed to confirm and quantify previously discovered eye proteins in both health and disease.

A proteomic approach to understanding the pathogenesis of idiopathic macular hole formation.

Idiopathic macular holes (IMH) are full-thickness defects of retinal tissue that cause severe vision loss due to disruption of the anatomic fovea. Abnormal vitreous traction is involved in the formation of macular holes. Both glial cells and hyalocytes contribute to epiretinal membrane formation in IMH. In order to gain further insight into the pathophysiology of IMH, we conducted a discovery phase investigation of the vitreous proteome in four patients with macular holes and six controls using one-dimensional gel fractionation and liquid chromatography-tandem mass spectrometry analyses on an Orbitrap Elite mass spectrometer. Of a total of 5912 vitreous proteins, 32 proteins had increased and 39 proteins had decreased expression in IMH compared with controls, using a false discovery rate approach with p value < 0.001 and q value < 0.05. IMH was associated with increased expression of proteins in the complement pathway, α-2-macroglobulin, a major inducer of Müller glial cell migration, fibrinogen, and extracellular matrix proteins, and decreased expression of proteins involved in protein folding and actin filament binding. A proteomic approach revealed proteins and biological pathways that may be involved in the pathogenesis of IMH and could be targeted for future studies.

Heart Failure-Related Hyperphosphorylation in the Cardiac Troponin I C Terminus Has Divergent Effects on Cardiac Function In Vivo.

BACKGROUND: In human heart failure, Ser199 (equivalent to Ser200 in mouse) of cTnI (cardiac troponin I) is significantly hyperphosphorylated, and in vitro studies suggest that it enhances myofilament calcium sensitivity and alters calpain-mediated cTnI proteolysis. However, how its hyperphosphorylation affects cardiac function in vivo remains unknown. METHODS AND RESULTS: To address the question, 2 transgenic mouse models were generated: a phospho-mimetic cTnIS200D and a phospho-silenced cTnIS200A, each driven by the cardiomyocyte-specific α-myosin heavy chain promoter. Cardiac structure assessed by echocardiography and histology was normal in both transgenic models compared with littermate controls (n=5). Baseline in vivo hemodynamics and isolated muscle studies showed that cTnIS200D significantly prolonged relaxation and lowered left ventricular peak filling rate, whereas ejection fraction and force development were normal (n=5). However, with increased heart rate or ß-adrenergic stimulation, cTnIS200D mice had less enhanced ejection fraction or force development versus controls, whereas relaxation improved similarly to controls (n=5). By contrast, cTnIS200A was functionally normal both at baseline and under the physiological stresses. To test whether either mutation impacted cardiac response to ischemic stress, isolated hearts were subjected to ischemia/reperfusion. cTnIS200D were protected, recovering 88±8% of contractile function versus 35±15% in littermate controls and 28±8% in cTnIS200A (n=5). This was associated with less cTnI proteolysis in cTnIS200D hearts. CONCLUSIONS: Hyperphosphorylation of this serine in cTnI C terminus impacts heart function by depressing diastolic function at baseline and limiting systolic reserve under physiological stresses. However, paradoxically, it preserves heart function after ischemia/reperfusion injury, potentially by decreasing proteolysis of cTnI.

A targeted proteomic assay for the measurement of plasma proteoforms related to human aging phenotypes.

Circulating polypeptides and proteins have been implicated in reversing or accelerating aging phenotypes, including growth/differentiation factor 8 (GDF8), GDF11, eotaxin, and oxytocin. These proteoforms, which are defined as the protein products arising from a single gene due to alternative splicing and PTMs, have been challenging to study. Both GDF8 and GDF11 have known antagonists such as follistatin (FST), and WAP, Kazal, immunoglobulin, Kunitz, and NTR domain-containing proteins 1 and 2 (WFIKKN1, WFIKKN2). We developed a novel multiplexed SRM assay using LC-MS/MS to measure five proteins related to GDF8 and GDF11 signaling, and in addition, eotaxin, and oxytocin. Eighteen peptides consisting of 54 transitions were monitored and validated in pooled human plasma. In 24 adults, the mean (SD) concentrations (ng/mL) were as follows: GDF8 propeptide, 11.0 (2.4); GDF8 mature protein, 25.7 (8.0); GDF11 propeptide, 21.3 (10.9); GDF11 mature protein, 16.5 (12.4); FST, 29.8 (7.1); FST cleavage form FST303, 96.4 (69.2); WFIKKN1, 38.3 (8.3); WFIKKN2, 32.2 (10.5); oxytocin, 1.9 (0.9); and eotaxin, 2.3 (0.5). This novel multiplexed SRM assay should facilitate the study of the relationships of these proteoforms with major aging phenotypes.