Orthogonal Partial Least-squares Analysis Research Articles

Characterizing the Impact of Cyanobacterial Blooms on the Photoreactivity of Surface Waters from New York Lakes: A Combined Statewide Survey and Laboratory Investigation.

Cyanobacterial blooms introduce autochthonous dissolved organic matter (DOM) into aquatic environments, but their impact on surface water photoreactivity has not been investigated through collaborative field sampling with comparative laboratory assessments. In this work, we quantified the apparent quantum yields (Φapp,RI) of reactive intermediates (RIs), including excited triplet states of dissolved organic matter (3DOM*), singlet oxygen (1O2), and hydroxyl radicals (•OH), for whole water samples collected by citizen volunteers from more than 100 New York lakes. Multiple comparisons tests and orthogonal partial least-squares analysis identified the level of cyanobacterial chlorophyll a as a key factor in explaining the enhanced photoreactivity of whole water samples sourced from bloom-impacted lakes. Laboratory recultivation of bloom samples in bloom-free lake water demonstrated that apparent increases in Φapp,RI during cyanobacterial growth were likely driven by the production of photoreactive moieties through the heterotrophic transformation of freshly produced labile bloom exudates. Cyanobacterial proliferation also altered the energy distribution of 3DOM* and contributed to the accelerated transformation of protriptyline, a model organic micropollutant susceptible to photosensitized reactions, under simulated sunlight conditions. Overall, our study provides insights into the relationship between the photoreactivity of surface waters and the limnological characteristics and trophic state of lakes and highlights the relevance of cyanobacterial abundance in predicting the photoreactivity of bloom-impacted surface waters.

Metabolomic Insight into Implications of Induction Chemotherapy Followed by Concomitant Chemoradiotherapy in Locally Advanced Head and Neck Cancer.

The present study compares two groups of locally advanced patients with head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (cCHRT), specifically those for whom it is a first-line treatment and those who have previously received induction chemotherapy (iCHT). The crucial question is whether iCHT is a serious burden during subsequent treatment for LA-HNSCC and how iCHT affects the tolerance to cCHRT. Of the 107 LA-HNSCC patients, 54 received cisplatin-based iCHT prior to cCHRT. The patients were clinically monitored at weekly intervals from the day before until the completion of the cCHRT. The 843 blood samples were collected and divided into two aliquots: for laboratory blood tests and for nuclear magnetic resonance (NMR) spectroscopy (a Bruker 400 MHz spectrometer). The NMR metabolites and the clinical parameters from the laboratory blood tests were analyzed using orthogonal partial least squares analysis (OPLS) and the Mann-Whitney U test (MWU). After iCHT, the patients begin cCHRT with significantly (MWU p-value < 0.05) elevated blood serum lipids, betaine, glycine, phosphocholine, and reticulocyte count, as well as significantly lowered NMR inflammatory markers, serine, hematocrit, neutrophile, monocyte, red blood cells, hemoglobin, and CRP. During cCHRT, a significant increase in albumin and psychological distress was observed, as well as a significant decrease in platelet, N-acetyl-cysteine, tyrosine, and phenylalanine, in patients who received iCHT. Importantly, all clinical symptoms (except the decreased platelets) and most metabolic alterations (except for betaine, serine, tyrosine, glucose, and phosphocholine) resolve until the completion of cCHRT. In conclusion, iCHT results in hematological toxicity, altered lipids, and one-carbon metabolism, as well as downregulated inflammation, as observed at the beginning and during cCHRT. However, these complications are temporary, and most of them resolve at the end of the treatment. This suggests that iCHT prior to cCHRT does not pose a significant burden and should be considered as a safe treatment option for LA-HNSCC.

Metal mixture and osteoporosis risk: Insights from plasma metabolite profiling

The pathophysiology of osteoporosis (OP) is influenced by exposure to nonessential harmful metals and insufficient or excessive intake of necessary metals. Investigating multiple plasma metals, metabolites, and OP risk among older adults may reveal novel clues of underlying mechanisms for metal toxicity on bone mass. A total of 294 adults ≥ 55 years from Wuhan communities were included. Plasma concentrations of 23 metals and metabolites were measured via inductively coupled plasma-mass spectrometry and global metabolite detection. To investigate the relationships between plasma metals, OP risk, and OP-related metabolites, three different statistical techniques were used: generalized linear regression model, two-way orthogonal partial least-squares analysis (O2PLS), and weighted quantile sum (WQS). The mean ages were 66.82 and 66.21 years in OP (n = 115) and non-OP (n = 179) groups, respectively. Of all 2999 metabolites detected, 111 differential between-group members were observed. The OP risk decreased by 58.5% (OR=0.415, 95% CI: 0.237, 0.727) per quartile increment in the WQS index indicative of metal mixture exposure. Consistency remained for bone mineral density (BMD) measurements. The O2PLS model identified the top five OP-related metabolites, namely, DG(18:2_22:6), 3-phenoxybenzoic acid, TG(16:1_16:1_22:6), TG(16:0_16:0_20:4), and TG(14:1_18:2_18:3), contributing most to the joint covariation between the metal mixture and metabolites. Significant correlations between each of them and the metal mixture were found using WQS regression. Furthermore, the five metabolites mediated the associations of the metal mixtures, BMD, and OP risk. Our findings shed additional light on the mediation functions of plasma metabolites in the connection between multiple metal co-exposure and OP pathogenesis and offer new insights into the probable mechanisms underpinning the bone effects of the metal mixture.

Spectrum-effect relationship between UPLC fingerprints and melanogenic effect of Ruta graveolens L

A total of 29 batches of R. graveolens were used in this study, their fingerprints were obtained by ultra-performance liquid chromatography (UPLC) and their melanogenesis activities were evaluated. The common peaks were identified by quadrupole-orbitrap high-resolution mass spectrometry (Q-Orbitrap-HRMS). Eleven coumarins, six alkaloids, three flavonoids, three phenolic acids, and four other compounds were found. The spectrum-effect relationships between R. graveolens’ chemical fingerprints, the melanin synthesis, and tyrosine’s activation activities were established through chemometrics methods which in detail principal component analysis (PCA), gray correlation analysis (GRA), bivariate correlation analysis (BCA) and orthogonal partial least squares analysis (OPLS). The results showed that P18 (bergapten), P22 (isoimperatorin), P15 (kokusaginine), P7 (rutin), P12 (psoralen), and P13 (graveolinine) were relevant to intracellular melanin synthesis activity and tyrosinase activity. Among them, P18 (bergapten), P15 (kokusaginine), and P12 (psoralen) were validated with good melanogenesis activities. This study provides a research basis for future quality control and medicinal application of R. graveolens.

Metabolome-Wide Association Study of Multiple Plasma Metals with Serum Metabolomic Profile among Middle-to-Older-Aged Chinese Adults.

Metal exposure has been associated with risk of various cardio-metabolic disorders, and investigation on the association between exposure to multiple metals and metabolic responses may reveal novel clues to the underlying mechanisms. Based on a metabolome-wide association study of 17 plasma metals with untargeted metabolomic profiling of 189 serum metabolites among 1992 participants within the Dongfeng-Tongji cohort, we replicated two metal-associated pathways, linoleic acid metabolism and aminoacyl-tRNA biosynthesis, with novel metal associations (false discovery rate, FDR < 0.05), and we also identified two novel pathways, including biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism, as associated with metal exposure (FDR < 0.05). Moreover, two-way orthogonal partial least-squares analysis showed that five metabolites, including aspartylphenylalanine, free fatty acid 14:1, uridine, carnitine C14:2, and LPC 18:2, contributed most to the joint covariation between the two data matrices (12.3%, 8.3%, 8.0%, 7.4%, and 7.3%, respectively). Further BKMR analysis showed significant positive joint associations of plasma Al, As, Ba, and Zn with aspartylphenylalanine and of plasma Ba, Co, Mn, and Pb with carnitine C14:2, when all the metals were at the 55th percentiles or above, compared with the median. We also found significant interactions between As and Ba in the association with aspartylphenylalanine (P for interaction = 0.048) and between Ba and Pb in the association with carnitine C14:2 (P for interaction < 0.001). Together, these findings may provide new insights into the mechanisms underlying the adverse health effects induced by metal exposure.

The changes of umami substances and influencing factors in preserved egg yolk: pH, endogenous protease, and proteinaceous substance.

The study investigated the changes of nucleotides, succinic acid, and free amino acids amounts in yolk and the causes leading to the changes after pickling to uncover the fundamental umami component of preserved egg yolk. The findings demonstrated that while the contents of 5′-adenosine monophosphate (AMP), 5′-cytidine monophosphate (CMP), 5′-guanosine monophosphate (GMP), 5′-uridine monophosphate (UMP), and succinic acid increased after slightly decreasing aspartic acid (Asp) content in preserved egg yolk increased gradually. The contents of 5′-inosine monophosphate (IMP) and other free amino acids were gradually decreased. Comparing the taste activity value (TAV), it was found that the single umami substance, succinic acid, played a key role in inducing the umami taste. In combination with the Spearman correlation analysis, it was shown that the proteinaceous substance, which is the most significant umami component in preserved egg yolk, tended to condense first and subsequently disintegrate in an alkaline environment. The orthogonal partial least squares analysis (OPLS) found that pH was also affected by the changes in proteinaceous substance. These findings offer suggestions for enhancing the pickling procedure and investigating the optimal pickling period for preserved eggs.

Dryness comparison of different fractions of Aurantii Fructus extract on normal mice and gastrointestinal motility disorder rats and spectrum-dryness study

Aurantii Fructus is a commonly used qi-regulating medicinal herb in China. Both traditional Chinese medicine theory and modern experimental research demonstrate that Aurantii Fructus has dryness effect, the material basis of which remains unclear. In recent years, spectrum-effect relationship has been widely employed in the study of active ingredients in Chinese medicinal herbs, the research ideas and methods of which have been constantly improved. Based on the idea of spectrum-effect study, the ultra-high perfor-mance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) fingerprints of different fractions of Aurantii Fructus extract were established for the identification of total components. Then, the dryness effects of the fractions on normal mice and gastrointestinal motility disorder(GMD) rats were systematically compared. Finally, principal component analysis(PCA), Pearson bivariate correlation analysis and orthogonal partial least squares analysis(OPLS) were integrated to identify the dryness components of Aurantii Fructusextract. The results showed that narirutin, naringin, naringenin, poncirin, oxypeucedanin, and eriodictyol-7-O-glucoside had significant correlations with and contributed to the expression of AQP2 in kidney, AQP3 in colon, and AQP5 in submandibular gland, which were the main dryness components in Aurantii Fructus.

The effect of strength-endurance training on serum and urine metabolic profiles of female adolescent volleyball athletes.

Limited investigations on metabolic responses to exercise training in female adolescent volleyball athletes exist. The aim of this study was to obtain serum and urine metabolite markers in female adolescent volleyball athletes within 2-week strength-endurance training using a metabolomics approach coupled with biochemical analysis, which would be potential biomarkers for evaluating the physiological state of athletes. Twelve female adolescent volleyball athletes were recruited for 2-week strength-endurance training. Differential serum and urine metabolic profiles between the pre- and post-training group were obtained on gas chromatography coupled to mass spectrometry (GC-MS) and data subsequently underwent orthogonal partial least-squares analysis (OPLS). Strength-endurance training exerted a significant influence on the athletes' serum and urine metabolic profiles. The changed metabolites were primarily involved in energy metabolism, lipid metabolism and amino acids metabolism. Results support the hypothesis that female athletes displayed an increased propensity to oxidize lipids as the major energy source. Exposure to strength-endurance training also led to a significant increase in cortisol, but a decrease in testosterone, indicating disordered hormone adjustment. Exercise-induced oxidative stress occurred, as was evidenced by the decrease in reduced glutathione, and increases in blood malondialdehyde and oxidized glutathione. Since the muscle damage markers creatine kinase and lactate dehydrogenase did not show significant changes, the training might not cause cell membrane damage and the athletes did not cross the adaptive injury level. By measurement of endogenous metabolites, the metabolomics study has the potential to reveal the global physiological changes in response to exercise training.

Gas chromatography/mass spectrometry-based metabolite profiling of coffee beans obtained from different altitudes and origins with various postharvest processing

Coffee is a popular beverage because of its pleasant aroma and distinctive flavor. The flavor of coffee results from chemical transformations influenced by various intrinsic and extrinsic factors, including altitude, geographical origin, and postharvest processing. Despite is the importance of grading coffee quality, there is no report on the dominant factor that influences the metabolomic profile of green coffee beans and the correlated metabolites for each factor. This study investigated the total metabolite profile of coffees from different altitudes and coffees subjected to different postharvest processing. Arabica green coffee beans obtained from different geographical origins and different altitudes (400 and 800m) and produced by different postharvest processes (dry, honey, and washed process) were used in this study. Coffee samples obtained from altitudes of 400-1600m above sea level from various origins that were produced by the washed method were used for further study with regard to altitudes. Samples were subjected to gas chromatography/mass spectrometry (GC/MS) analysis and visualized using principal component analysis (PCA) and orthogonal partial least squares (OPLS) regression analysis. The PCA results showed sample separation based on postharvest processing in PC1 and sample separation based on altitude in PC2. A clear separation between samples from different altitudes was observed if the samples were subjected to the same postharvest processing method, and the samples were of the same origin. Based on this result, OPLS analysis was conducted using coffee samples obtained from various altitudes with the same postharvest processing. An OPLS model using altitude as a response variable and 79 metabolites annotated from the GC/MS analysis as an explanatory variable was constructed with good R2 and Q2 values. Postharvest processing was found to be the dominant factor affecting coffee metabolite composition; this was followed by geographical origin and altitude. The metabolites glutamic acid and galactinol were associated with the washed and honey process, while glycine, lysine, sorbose, fructose, glyceric acid, and glycolic acid were associated with the dry process. Two metabolites with high variable influence on projection scores in the OPLS model for altitude were inositol and serotonin, which showed positive and negative correlations, respectively. This is the first study to report characteristic coffee metabolites obtained from different altitudes.

Impact of air‐frying on the plasmalogens deterioration and oxidation in oyster revealed by mild acid hydrolysis and HILIC‐MS‐based lipidomics analysis

Oyster is rich in plasmalogens that are ether phospholipids with biological functions to human body. Air-frying is a popular technique for preparing delicious oyster but makes the plasmalogens vulnerable to oxidation. In this study, the effect of air-frying processing on plasmalogens oxidation was studied by lipidomic approach. Plasmalogens were always mixed with normal phospholipids, thus the lipid extract was treated with mild acid hydrolysis to rapidly degrade plasmalogens owing to the acid lability of vinyl ether linkage at sn-1 position. After hydrophilic interaction chromatography MS/MS analysis, there were three plasmalogen classes, plasmanylcholine, plasmanylethanolamine, and plasmanylinositol, completely separated, and each plasmalogen molecular species was identified and quantified. It indicated that the content of plasmalogens underwent an obvious decrease during the air-frying process. To weaken such effect, the influence of air-frying temperature was further inspected by multivariate statistical analyses. The main variables, including the ions of m/z 756.4927, 784.5486, 828.5812, etc., were revealed by unsupervised principle component analysis, supervised orthogonal partial least-square analysis, and variable importance in projection plot. As a conclusion, air-frying has health benefits in reducing fat content but destructive to plasmalogens, thus interventions are recommended to prevent the degradation of plasmalogens.

Estimation of Early Postmortem Interval of Asphyxial Death Rats at Different Ambient Temperatures by GC-MS-Based Metabolomics

Objective To establish the orthogonal partial least square （OPLS） model for the estimation of early postmortem interval （PMI） of asphyxial death rats in four ambient temperatures based on gas chromatography-mass spectrometry （GC-MS） metabolomics. Methods The 96 rats were divided into four temperature groups （5 ℃, 15 ℃, 25 ℃ and 35 ℃）. Each temperature group was further divided into 3 h, 6 h, 12 h and 24 h after death, and 6 other rats were taken as the control group. The cardiac blood was collected at the set time points for the four temperature groups and 0 h after death for the control group for the metabolomics analysis by GC-MS. By OPLS analysis, the variable importance in projection （VIP）>1 and the result of Kruskal-Wallis test P<0.001 were used to screen out the differential metabolite related to PMIs in the cardiac blood of rats of different temperature groups. Then OPLS regression models of different temperature groups were established with these metabolites. At the same time, a prediction group for investigating the prediction ability of these models was set up. Results Through the analysis of OPLS, 18, 15, 24 and 30 differential metabolites （including organic acids, amino acids, sugars and lipids） were screened out from the rats in groups of 5 ℃, 15 ℃, 25 ℃ and 35 ℃, respectively. The prediction results of the four temperature group models showed that the prediction deviation of 5 ℃ model was larger than that of other groups. The prediction results of other temperature groups were satisfactory. Conclusion There are some differences in the changes of metabolites in cardiac blood of rats at different ambient temperatures. The influence of ambient temperature should be investigated in the study of PMI estimation by metabolomics, which may improve the accuracy of PMI estimation.

Real-time assessing the lipid oxidation of prawn (Litopenaeus vannamei) during air-frying by iKnife coupling rapid evaporative ionization mass spectrometry

Air-frying is a novel way of preparing fried food but easily induces lipid oxidation because of the direct contact between the raw product and circulated hot air in the fryer chamber. In this study, a lipidomics approach for real-time monitoring and assessing the dynamic oxidation characteristics of lipids in prawn was explored by an iKnife coupled to rapid evaporative ionization mass spectrometry (REIMS) method. The effect of air-frying on the lipid oxidation in prawn at different temperatures was investigated. The obtained profiling data were statistically analyzed by multivariate statistical analysis, including principle component analysis (PCA) and orthogonal partial least-square analysis (OPLS-DA), which showed that the difference in fatty acid (FA) and phospholipid molecular species (PMS) was statistically significant (p < 0.05) with R2(cum) and Q2 (cum) values > 0.8. Based on the shared and unique structures plot, the ions of m/z 255.23, 764.52, 766.53, and 816.55 were regarded as the major contributors for the discrimination of various processed prawn samples, and their effectiveness was further verified by receiver operating characteristic (ROC) curve. The results indicated that the proposed iKnife-REIMS could serve as an in-situ and real-time method for monitoring and assessing the lipids, and be employed as a front-line fast detection mean to ensure the fried product quality.

Analysis of volatile compound change in tuna oil during storage using a laser irradiation based HS-SPME-GC/MS

Tuna oil (TO) is susceptible to oxidation thus induce unpleasant flavor during storage. Herein, a novel and efficient laser irradiation desorption headspace solid-phase microextraction coupling gas chromatography-mass spectrometry method was developed for fast analysis of flavor change in TO at different storage periods. The data were statistically analyzed by multivariate statistical analyses, including principle component analysis (PCA) and orthogonal partial least-square analysis (OPLS-DA), which showed superb classification accuracy and validation (R2(X) = 0.915, Q2 = 0.834) and was further verified by permutation test. The variation of volatile compounds in TOs along with the extension of storage time was statistically analyzed to be significant (p < 0.05). Nonanal, heptanal, 2-octanone, and hexadecanoic acid, ethyl ester were regarded as the dominant indicators with significant effect on the data matrix. The LID-HS-SPME GC/MS technique could be employed as a front-line fast detect method to ensure the lipid quality.

Analysis of volatile organic compounds released from SW480 colorectal cancer cells and the blood of tumor-bearing mice.

BackgroundVolatile organic compound (VOC) analysis provides an elegant approach for colorectal cancer screening. An organic compound with a high vapor pressure or volatility can be detected in the headspace of cancer cells or blood samples. Therefore, analyzing VOCs in the blood of rats inoculated with colorectal cancer tissue and in SW480 medium from cultured colorectal cancer cells may provide accurate results.MethodsAfter collecting venous blood from rats inoculated with cancer cells at different times, the cancer tissue was removed from the inoculated rats, and the medium was harvested from the cancer cells and cultured in the presence or absence of a chemotherapy drug of intestinal epithelial cells. We used solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) to analyze the headspace of the blood and media to evaluate the VOC profiles. Statistical analysis was conducted using principal component analysis (PCA) and orthogonal partial least-squares analysis (OP-LSDA).ResultsThe in vivo and in vitro analyses of the colorectal cancer samples revealed a variety of compounds, such as cyclohexanone, 1-hexanol, 2-ethyl-, butylated hydroxytoluene, cyclotrisiloxane, hexamethyl-, pentanoic acid, 2,2,4-trimethyl-3-hydroxy-isobutyl ester and acetone. Butylated hydroxytoluene is unique with regard to its presence during tumor growth and resection; it is also present during tumor cell growth and necrosis. Acetone showed unique trends in the in vivo experimental group.ConclusionsBy analyzing VOC fingerprints related to colorectal cancer (CRC), we found that butylated hydroxytoluene and acetone have unique signatures that may provide the basis for clinical diagnosis and disease assessment.

Development of an intelligent surgical knife rapid evaporative ionization mass spectrometry based method for real-time differentiation of cod from oilfish

Oilfish is banned in some countries because of the unpleasant side-effects of eating oilfish. However, oilfish was easily mislabeled and sold as cod due to their closed appearance. In this study, an in situ and real-time method was developed to distinguish cod from oilfish by coupling intelligent surgical knife (iKnife) and rapid evaporative ionization mass spectrometry (REIMS). The fillets collected from the same position of adult fishes were analyzed directly without sample preparation. The iKnife-REIMS conditions were optimized as cutting speed ca. 5 mm·s−1 and stripe length 2 cm, power output 30 W, and flow rate of auxiliary solvent (propan-2-ol) 100 μL·min–1. 200 spectral data from oilfish and cod was acquired in negative ionization mode and the data was processed by background subtraction, peak detection, and absolute counts calculation, which were further statistically analyzed by multivariate statistical analyses, including principal component analysis (PCA) and orthogonal partial least-square analysis (OPLS-DA). The major contributors of cluster separation were verified by permutation test and receiver operating characteristic (ROC) analysis. The identities of oilfish and cod (Greenland cod, Pacific cod, and Atlantic cod) were successfully recognized with accuracy 96–100%. This study filled the application niche of REIMS in cod authenticity and paved the way for the administration of food security and quality for related functional departments and bureaus.

Untargeted Metabolomics Based on GC-MS and Chemometrics: A New Tool for the Early Diagnosis of Strawberry Anthracnose Caused by Colletotrichum theobromicola.

To prevent the spread of anthracnose in strawberry plants and characterize the metabolic changes occurring during plant-pathogen interactions, we developed a method for the early diagnosis of disease based on an analysis of the metabolome by gas chromatography-mass spectrometry. An examination of the metabolic profile revealed 189 and 202 total ion chromatogram peaks for the control and inoculated plants, respectively. A partial least squares discriminant analysis (PLS-DA) model was conducted for the reliable and accurate discrimination between healthy and diseased strawberry plants, even in the absence of disease symptoms (e.g., early stages of infection). ANOVA (analysis of variance) and orthogonal partial least squares analysis (OPLS) identified 20 metabolites as tentative biomarkers of Colletotrichum theobromicola infection (e.g., citric acid, d-xylose, erythrose, galactose, gallic acid, malic acid, methyl α-galactopyranoside, phosphate, and shikimic acid). At least some of these potential biomarkers may be applicable for the early diagnosis of anthracnose in strawberry plants. Moreover, these metabolites may be useful for characterizing pathogen infections and plant defense responses. This study confirms the utility of metabolomics research for developing diagnostic tools and clarifying the mechanism underlying plant-pathogen interactions. Furthermore, the data presented herein may be relevant for developing new methods for preventing anthracnose in strawberry seedlings cultivated under field conditions.

Plasma Protein Pattern Correlates With Pain Intensity and Psychological Distress in Women With Chronic Widespread Pain.

Objectives: Although generalized muscle pain, tiredness, anxiety, and depression are commonly present among chronic widespread pain (CWP) patients, the molecular mechanisms behind CWP are not fully elucidated. Moreover, the lack of biomarkers often makes diagnosis and treatment problematic. In this study, we investigated the correlation between pain intensity, psychological distress, and plasma proteins among CWP patients and controls (CON).Methods: The plasma proteome of CWP (n = 15) and CON (n = 23) was analyzed using two-dimensional gel electrophoresis. Orthogonal Partial Least Square analysis (OPLS) was used to determine proteins associated with pain intensity (numeric rating scale) in CWP and psychological distress (Hospital and Depression Scale, HADS) in CWP and CON. Significant proteins were identified by MALDI-TOF and tandem MS.Results: In CWP, pain intensity was associated with plasma proteins mostly involved in metabolic and immunity processes (e.g., kininogen-1, fibrinogen gamma chain, and ceruloplasmin), and psychological distress was associated with plasma proteins related to immunity response, iron ion, and lipid metabolism (e.g., complement factor B, complement C1r subcomponent, hemopexin, and clusterin).Discussion: This study suggests that different plasma protein patterns are associated with different pain intensity and psychological distress in CWP. Proteins belonging to the coagulation cascade and immunity processes showed strong associations to each clinical outcome. Using the plasma proteome profile of CWP to study potential biomarker candidates provides a snapshot of ongoing systemic mechanisms in CWP.

PO-58 The influence of different intensity exercise on DEN-induced hepatocellular carcinoma and liver metabonomic study

Objective To study the influence of high internal intensity exercise and long-term moderate intensity endurance exercise on DEN-induced hepatocellular carcinoma (HCC) by metabonomics approach, and compare the anti-tumor effect between the different intensity exercise. &#x0D; Methods From 8 to 26 weeks of age, mice with DEN treatment run on the treadmill at different intensity. NC: injection saline only. DEN: injection DEN only. HIT: treatment DEN, running on the treadmill at 1.5km/h, alternating run 2 minutes and rest 2 minutes for 40 minutes once a day, 5 days a week. ET: treatment DEN, running on the treadmill at o.8 km/h for 40 minutes once a day, 5 days a week. Gas chromatograph time-of-flight mass spectrometry (GC−TOFMS) test liver samples of mice and multi-dimensional statistical methods fond differential metabolites in all group.&#x0D; Results We observed that tumor incidence was similar between DEN and HIT; however, it was signicicantly smaller in ET compared to DEN and HIT. Orthogonal partial least squares analysis (OPLS) model was generated based on identified metabolites and showed clear discrimination from only DEN injection group and endurance exercise group, endurance exercise group and high intensity interval exercise group. Compared to DEN group, the level of galactinol, timonacic, glycine, cholesterol, carbamate and palmitic acid significantly decreased in endurance exercise group. Nevertheless, the level of malonic acid, ornithine and glutamic acid obviously increased in endurance group. &#x0D; Conclusions Long-term endurance exercise inclines the hepatic tumor incidence by regulating the level of liver palmitic acid and glutamic acid metabolism . In addition, high intensity interval exercise does not have the effect to prevent tumor development.

Diterpenoid fingerprints in pine foliage across an environmental and chemotypic matrix: Isoabienol content is a key trait differentiating chemotypes

Diterpenoids constitute an important part of oleoresin in conifer needles, but the environmental and genetic controls on diterpenoid composition are poorly known. We studied the presence of diterpenoids in four pine populations spanning an extensive range of nitrogen (N) availability. In most samples, isoabienol was the main diterpenoid. Additionally, low contents of (Z)-biformene, abietadiene isomers, manoyl oxide isomers, labda-7,13,14-triene and labda-7,14-dien-13-ol were quantified in pine needles. According to the occurrence and content of diterpenoids it was possible to distinguish ‘non diterpenoid pines’, ‘high isoabienol pines’, ‘manoyl oxide – isoabienol pines’ and ‘other diterpenoid pines’. ‘Non diterpenoid pines’, ‘high isoabienol pines’ and ‘other diterpenoid pines’ were characteristic to the dry forest, yet the majority of pines (>80%) of the bog Laeva represented ‘high isoabienol pines’. ‘Manoyl oxide – isoabienol pines’ were present only in the wet sites. Additionally, orthogonal partial least-squares analysis showed, that in the bogs foliar nitrogen content per dry mass (NM) correlated to diterpenoids. Significant correlations existed between abietadienes, isoabienol and foliar NM in ‘manoyl oxide – isoabienol pines’, and chemotypic variation was also associated by population genetic distance estimated by nuclear microsatellite markers. Previously, the presence of low and high Δ-3-carene pines has been demonstrated, but the results of the current study indicate that also diterpenoids form an independent axis of chemotypic differentiation. Further studies are needed to understand whether the enhanced abundance of diterpenoids in wetter sites reflects a phenotypic or genotypic response.

A metabolomics approach to study the dual modulation by characterization of chemical alteration during processing of Gardeniae Fructus using UPLC-ESI-QTOF

Dual modulation is an interesting phenomenon that may occur during Chinese Materia Medica (CMM) processing whereby the crude and processed products have completely opposite therapeutic effects in vivo due to chemical component alteration. Therefore, a comprehensive study of the chemical alteration in order to shed light on the reason behind dual modulation is of critical importance. Metabolomics employs an untargeted approach to obtain an overview on secondary metabolites in multi-component systems using high resolution LC-MS2, which fulfills the requirement of a comprehensive analysis to clarify the mechanism of dual modulation. Gardeniae Fructus (GF), is one of the many widely used medicines across Asia, and its processed product exhibits completely opposite therapeutic effects on blood stasis. Therefore, we chose crude and processed GF to examine changes in secondary metabolites using UPLC-ESI-QTOF. In the subsequent chemometric analysis, both principal component analysis (PCA, unsupervised feature extraction) and orthogonal partial least-squares analysis (OPLSA, supervised feature extraction) were used to find out the chemical changes during processing. Iridoid Glycosides – jaminoside B, genipine-1-β-gentiobioside, 6α-hydroxygeniposide, and geniposide – and other ingredients such as mannitol and crocin were found to have decreased three to four fold in processed GF compared to crude GF, whereas another iridoid glycoside with a carboxyl group, mussaenosidic acid, was found to increase two fold in the processed product. This rapid yet reliable screening method can be also applied to other CMM to characterize the chemical changes and further explain the reasons behind dual modulation.