Changes In Metabolic Biomarkers Research Articles

LC-MS/MS metabolomic profiling of the protective butylphthalide effect in cerebral ischemia/reperfusion mice

ObjectivesThis study was designed to investigate metabolic biomarker changes and related metabolic pathways of Butylphthalide (NBP) on cerebral ischemia/reperfusion. MethodsIn this study, a mouse cerebral ischemia/reperfusion (I/R) model was prepared using the middle cerebral artery occlusion method, and neurobehavioral score and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining experiments were used to confirm the obvious NBP anti-cerebral ischemia effect. The protective effect of NBP in the mouse cerebral I/R model and its metabolic pathway and mechanism were investigated using mouse blood samples. ResultsThe metabolic profiles of mice in the I/R+NBP, I/R, and sham groups were significantly different. Under the condition that I/R vs. sham was downregulated and I/R + NBP vs. I/R was upregulated, 88 differential metabolites, including estradiol, ubiquinone-2, 2-oxoarginine, and L-histidine trimethylbetaine, were screened and identified. The related metabolic pathways involved arginine and proline metabolism, oxidative phosphorylation, ubiquitin and other terpenoid-quinone biosynthesis, and estrogen signaling. ConclusionsMetabolomics was used to elucidate the NBP mechanism in cerebral ischemia treatment in mice, revealing synergistic NBP pharmacological characteristics with multiple targets.

A ketogenic diet reduces mechanical allodynia and improves epidermal innervation in diabetic mice.

Dietary interventions are promising approaches to treat pain associated with metabolic changes because they impact both metabolic and neural components contributing to painful neuropathy. Here, we tested whether consumption of a ketogenic diet could affect sensation, pain, and epidermal innervation loss in type 1 diabetic mice. C57Bl/6 mice were rendered diabetic using streptozotocin and administered a ketogenic diet at either 3 weeks (prevention) or 9 weeks (reversal) of uncontrolled diabetes. We quantified changes in metabolic biomarkers, sensory thresholds, and epidermal innervation to assess impact on neuropathy parameters. Diabetic mice consuming a ketogenic diet had normalized weight gain, reduced blood glucose, elevated blood ketones, and reduced hemoglobin-A1C levels. These metabolic biomarkers were also improved after 9 weeks of diabetes followed by 4 weeks of a ketogenic diet. Diabetic mice fed a control chow diet developed rapid mechanical allodynia of the hind paw that was reversed within a week of consumption of a ketogenic diet in both prevention and reversal studies. Loss of thermal sensation was also improved by consumption of a ketogenic diet through normalized thermal thresholds. Finally, diabetic mice consuming a ketogenic diet had normalized epidermal innervation, including after 9 weeks of uncontrolled diabetes and 4 weeks of consumption of the ketogenic diet. These results suggest that, in mice, a ketogenic diet can prevent and reverse changes in key metabolic biomarkers, altered sensation, pain, and axon innervation of the skin. These results identify a ketogenic diet as a potential therapeutic intervention for patients with painful diabetic neuropathy and/or epidermal axon loss.

Investigation of the idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. through metabolomics using GC-MS

BackgroundThe idiosyncratic hepatotoxicity of Polygonum multiflorum (PM) has attracted considerable interest, but the idiosyncratically hepatotoxic components and endogenous metabolite changes resulting from idiosyncratic hepatotoxicity of PM are not well understood. The aim of this study was to identify the idiosyncratically hepatotoxic components and potential endogenous metabolic biomarkers for PM-induced liver injury.MethodsSerum biochemical indicators and hematoxylin and eosin (H&E) staining were evaluated to identify pathological changes. Gas chromatography/mass spectrometry (GC-MS) was performed to identify changes in metabolic biomarkers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was applied to determine group clustering trends and differential metabolites.ResultsThe results for the liver index, the liver function index and liver pathology showed that Polygonum multiflorum ethanol extract (PME), 50% ethanol elution fractions and tetrahydroxystilbene glucoside (TSG) from PME can induce idiosyncratic hepatotoxicity. TSG was the main idiosyncratically hepatotoxic component. Forty endogenous metabolites were identified in the rat liver. Six biomarkers, including lower levels of L-valine and higher levels of 3-hydroxybutyric acid, hexadecanoic acid, ribose, phosphoric acid and oxalic acid, were related to PM-induced liver injury. These differential biomarkers led to disruptions in amino acid, fatty acid, oxalate, energy and glucose metabolism. A total of 32 types of endogenous metabolites were identified in rat serum. Ten biomarkers were related to the liver injury induced by TSG, including lower levels of L-valine and L-proline and higher levels of urea, caproic acid, DL-malic acid, D-mannose, 3-hydroxybutyric acid, D-galactose, octadecane and hexadecanoic acid. These differential biomarkers led to disruptions in amino acid, glucose and fat metabolism. The mechanism of idiosyncratic hepatotoxicity in PM involves TSG-induced disruptions in amino acid metabolism, lipid metabolism, energy metabolism and glucose metabolism.ConclusionsThese findings reflect the material basis and metabolic mechanism of idiosyncratic PM hepatotoxicity.

The Effects of a Mediterranean Diet Intervention on Targeted Plasma Metabolic Biomarkers among US Firefighters: A Pilot Cluster-Randomized Trial.

Metabolomics is improving the understanding of the mechanisms of the health effects of diet. Previous research has identified several metabolites associated with the Mediterranean Diet (MedDiet), but knowledge about longitudinal changes in metabolic biomarkers after a MedDiet intervention is scarce. A subsample of 48 firefighters from a cluster-randomized trial at Indianapolis fire stations was randomly selected for the metabolomics study at 12 months of follow up (time point 1), where Group 1 (n = 24) continued for another 6 months in a self-sustained MedDiet intervention, and Group 2 (n = 24), the control group at that time, started with an active MedDiet intervention for 6 months (time point 2). A total of 225 metabolites were assessed at the two time points by using a targeted NMR platform. The MedDiet score improved slightly but changes were non-significant (intervention: 24.2 vs. 26.0 points and control group: 26.1 vs. 26.5 points). The MedDiet intervention led to favorable changes in biomarkers related to lipid metabolism, including lower LDL-C, ApoB/ApoA1 ratio, remnant cholesterol, M-VLDL-CE; and higher HDL-C, and better lipoprotein composition. This MedDiet intervention induces only modest changes in adherence to the MedDiet and consequently in metabolic biomarkers. Further research should confirm these results based on larger study samples in workplace interventions with powerful study designs.

Effects of Internet Cognitive-Behavioral Therapy on Depressive Symptoms and Surrogates of Cardiovascular Risk in Human Immunodeficiency Virus: A Pilot, Randomized, Controlled Trial.

BackgroundDepression is associated with an increased risk of cardiovascular disease in human immunodeficiency virus (HIV). We hypothesized that reducing depressive symptoms would improve HIV-related cardiovascular risk.MethodsWe conducted a single-center, randomized (1:1), controlled, parallel-group, assessor-blinded, pilot trial comparing Beating the Blues US (BtB)—an evidence-based, 8-session, internet cognitive-behavioral therapy for depression—with usual care (UC) in HIV-positive participants receiving virologically suppressive antiretroviral therapy and with Patient Health Questionnaire (PHQ)-9 scores ≥10. The primary endpoint was change in brachial artery flow-mediated dilation (FMD) at 12 weeks. Secondary endpoints were FMD change at 24 weeks and inflammation, coagulation, and metabolic biomarker changes at 12 and 24 weeks.ResultsFifty-four participants were randomized (27 in each arm). Mean reductions in PHQ-9 scores were significantly greater with BtB versus UC at 12 weeks (−5.60 vs −1.52; P = .007) and 24 weeks (−6.00 vs −1.38; P = .008); reductions in the Hopkins Symptom Checklist Depression Scale-20 scores were also significantly greater with BtB versus UC at 24 weeks (−0.72 vs −0.35; P = .029). Changes in FMD between arms were not significantly different at 12 or 24 weeks. Significantly larger reductions in soluble (s)CD14 and sCD163 with BtB versus UC were found at 12 and 24 weeks, respectively.ConclusionsCompared with UC, internet cognitive-behavioral therapy using BtB resulted in greater improvements in depressive symptoms and monocyte activation markers but did not improve FMD in this pilot trial. These data support performing larger studies to determine the potential salutatory effects of behavioral therapies for depression on HIV-related inflammation.

Metabolomics coupled with integrative pharmacology reveals the therapeutic effect of l-borneolum against cerebral ischaemia in rats.

This study aimed to investigate metabolic biomarker changes and related metabolic pathways before and after treatment with l-borneolum in cerebral ischaemic rats. Rats were subjected to pMCAO surgery. The Zea-Longa scoring method was used to evaluate neurological deficits. TTC staining was used to observe cerebral infarction. HE staining was used to observe the pathological changes in brain tissue. The metabolomics method was used to analyse the changes in metabolism. The pharmacology changes of the H-B group were significantly different from those of the vehicle group. Moreover, according to the metabolomics method, identification of potential biomarkers in cerebral ischaemia treatment showed that the levels of l-valine and l-arginine were increased while the levels of N-succinyl-L,L-2,6-diaminopimelate and LysoPC (18:1(9Z)) were reduced, which were related to energy metabolism. Simultaneously, thermogenesis and bile secretion levels were inhibited by l-borneolum. Furthermore, elevated level of methotrexate might be related to an anti-inflammatory effect. The therapeutic effect of l-borneolum on cerebral ischaemia might be associated with the regulation of energy metabolism, thermogenesis and bile secretion. These metabolic changes and the core target changes, as well as the metabolic-target pathway network, help to elucidate the mechanisms governing the effect of l-borneolum on cerebral ischaemia.

Effects of six months of aerobic and resistance training on metabolic markers and bone mineral density in older men on androgen deprivation therapy for prostate cancer

BackgroundAndrogen deprivation therapy (ADT) for prostate cancer (PCa) is associated with metabolic perturbations and declines in bone mineral density (BMD). Exercise interventions provide multiple health benefits to older men on ADT; however, their effect on metabolic biomarkers and BMD remains unclear. MethodsA secondary analysis of a phase II randomized controlled trial was conducted to assess the effect of a six-month moderate-intensity aerobic and resistance exercise program on metabolic biomarkers and BMD in men on ADT. Participants were randomized to three different exercise delivery models: personal training; supervised group exercise; or home-based exercise. Analysis of metabolic biomarkers (lipid profile and glucose) was conducted at baseline, six and twelve months. BMD of the lumbar spine, femoral neck and hip were assessed at baseline and twelve months. Both within- and between-group analyses of change scores adjusted for baseline values were performed. ResultsForty-eight men (mean age 69.8y) were enrolled. Baseline values of metabolic biomarkers and BMD were comparable between groups and the three groups were combined for the primary analysis. At six months, no changes in metabolic biomarkers were found; however, at twelve months low-density lipoprotein (+0.28 mmol/L; 95%CI, 0.04 to 0.51) and total cholesterol (+0.31 mmol/L; 95%CI, 0.00 to 0.61) were significantly increased from baseline. No changes were found in BMD. In a secondary between-group analysis, no improvements were observed for any metabolic biomarker or BMD measurement. ConclusionsDifferent exercise prescription parameters (modality and intensity) or combined diet/exercise interventions may be needed to foster favorable metabolic and skeletal adaptations during ADT.

Metabolomics profiling of Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata extracts using UPLC-Q/TOF-MS

BackgroundThe side effects caused by Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP) have often appeared globally. There is no research on the changes of endogenous metabolites among PMR- and PMRP-treated rats. The aim of this study was to evaluate the varying metabolomic effects between PMR- and PMRP-treated rats. We tried to discover relevant differences in biomarkers and endogenous metabolic pathways.MethodsHematoxylin and eosin staining and immunohistochemistry staining were performed to find pathological changes. Biochemical indicators were also measured, one-way analysis of variance with Dunnett’s multiple comparison test was used for biochemical indicators comparison among various groups. Metabolomics analysis based on ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-Q/TOF-MS) was performed to find the changes in metabolic biomarkers. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to reveal group clustering trend, evaluate and maximize the discrimination between the two groups. MetaboAnalyst 4.0 was performed to find and confirm the pathways.ResultsPMR extracts exhibited slight hepatotoxic effects on the liver by increasing aspartate and alanine aminotransferase levels. Twenty-nine metabolites were identified as biomarkers, belonging to five pathways, including alpha-linolenic acid metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, arginine and proline metabolism, and primary bile acid biosynthesis.ConclusionThis study provided a comprehensive description of metabolomic changes between PMR- and PMRP-treated rats. The underlying mechanisms require further research.

Metabolic trajectories across early adolescence: differences by sex, weight, pubertal status and race/ethnicity

Background: Biomarkers of cardiovascular and metabolic risk track from adolescence into adulthood, therefore characterising the direction and magnitude of these changes is an important first step to identifying health trajectories that presage future disease risk.Aim: To characterise changes in metabolic biomarkers across early adolescence in a multi-ethnic cohort.Subjects and methods: Among 891 participants in Project Viva we estimated changes in insulin resistance (HOMA-IR), adipokines, lipids, and SBP between ages 6–10 years and 11–16 years. Next, we used multivariable linear regression to examine associations of sex, baseline overweight/obesity, baseline pubertal status and race/ethnicity with change in the biomarkers during follow-up.Results: Boys exhibited a larger decrement in adiponectin (−0.66 [95% CI = −1.14, −0.18)] ng/mL) and a greater increase in SBP (3.20 [2.10, 4.30] mmHg) than girls. Overweight/obese participants experienced larger increases in HOMA-IR, leptin, and triglycerides; and a steeper decrement in HDL. Pubertal youth showed larger decrements in total and LDL cholesterol than their pre-pubertal counterparts. In comparison to White participants, Black youth experienced a larger magnitude of increase in HOMA-IR, and Hispanic youth exhibited larger decrements in adiponectin and HDL.Conclusions: Change in metabolic biomarkers across early adolescence differed by sex, weight status, pubertal status and race/ethnicity. Some of the metabolic changes may reflect normal physiological changes of puberty, while others may presage future disease risk. Future studies are warranted to link metabolic changes during adolescence to long-term health.

Intense Exercise for Survival among Men with Metastatic Castrate-Resistant Prostate Cancer (INTERVAL-GAP4): a multicentre, randomised, controlled phase III study protocol

IntroductionPreliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance...

Branched Chain Amino Acids, Androgen Hormones, and Metabolic Risk Across Early Adolescence: A Prospective Study in Project Viva.

ObjectiveTo examine associations of two obesity-related metabolite patterns with changes in metabolic biomarkers during early adolescence.MethodsUsing multivariable linear regression, we examined associations of a branched chain amino acid (BCAA) and androgen hormone patterns with changes in glycemia (fasting glucose, insulin, HOMA-IR), adipokines (leptin, adiponectin), inflammation (C-reactive protein, interleukin-6), lipid profile, and blood pressure during ~5 years follow-up among 213 children aged 6–10 years at baseline. We adjusted for baseline age, pubertal status, biomarker level, and BMI percentile; and age at follow-up. We also tested for interactions with sex and baseline BMI percentile.ResultsMedian age at baseline was 7.7 years; 48.8% were boys. In adjusted models, each 1 unit of the BCAA pattern corresponded with a 4.82 (95% CI: 0.92, 8.71) mg/dL decrease in fasting glucose in boys. In girls, the BCAA pattern was associated with an increase in triglycerides (4.17 [0.03, 8.32] mg/dL). The androgen pattern was associated with decreased leptin (−2.35 [−4.34, −0.35] ng/dL) and increased CRP (0.28 [0.03, 0.54] mg/dL) in girls. These relationships did not differ by baseline BMI percentile.ConclusionsThe BCAA and androgen hormone metabolite patterns are related to changes in metabolic parameters in a sex-specific manner during early adolescence.

Metabolic characterization of menopause: cross-sectional and longitudinal evidence

BackgroundWomen who experience menopause are at higher cardiometabolic risk and often display adverse changes in metabolic biomarkers compared with pre-menopausal women. It remains elusive whether the changes in cardiometabolic biomarkers during the menopausal transition are due to ovarian aging or chronological aging. Well-conducted longitudinal studies are required to determine this. The aim of this study was to explore the cross-sectional and longitudinal associations of reproductive status, defined according to the 2012 Stages of Reproductive Aging Workshop criteria, with 74 metabolic biomarkers, and establish whether any associations are independent of age-related changes.MethodsWe determined cross-sectional associations of reproductive status with metabolic profiling in 3,312 UK midlife women. In a subgroup of 1,492 women who had repeat assessments after 2.5 years, we assessed how the change in reproductive status was associated with the changes in metabolic biomarkers. Metabolic profiles were measured by high-throughput quantitative nuclear magnetic resonance metabolomics. In longitudinal analyses, we compared the change in metabolic biomarkers for each reproductive-status category change to that of the reference of being pre-menopausal at both time points. As all women aged by a similar amount during follow-up, these analyses contribute to distinguishing age-related changes from those related to change in reproductive status.ResultsConsistent cross-sectional and longitudinal associations of menopause with a wide range of metabolic biomarkers were observed, suggesting the transition to menopause induces multiple metabolic changes independent of chronological aging. The metabolic changes included increased concentrations of very small very low-density lipoproteins, intermediate-density lipoproteins, low-density lipoproteins (LDLs), remnant, and LDL cholesterol, and reduced LDL particle size, all toward an atherogenic lipoprotein profile. Increased inflammation was suggested via an inflammatory biomarker, glycoprotein acetyls, but not via C-reactive protein. Also, levels of glutamine and albumin increased during the transition. Most of these metabolic changes seen at the time of becoming post-menopausal remained or became slightly stronger during the post-menopausal years.ConclusionsThe transition to post-menopause has effects on multiple circulating metabolic biomarkers, over and above the underlying age trajectory. The adverse changes in multiple apolipoprotein-B-containing lipoprotein subclasses and increased inflammation may underlie women’s increased cardiometabolic risk in their post-menopausal years.

Zearalenone induced embryo and neurotoxicity in zebrafish model (Danio rerio): Role of oxidative stress revealed by a multi biomarker study

In the present study, we evaluated the zearalenone induced adverse effects in zebrafish embryos using various endpoints like embryo toxicity, heart rate, oxidative stress indicators (reactive oxygen species (ROS), lipid peroxidation (LPO), Nitric oxide (NO)), antioxidant responses (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase enzyme (GST) and reduced glutathione (GSH), metabolic biomarkers (lactate dehydrogenase (LDH) and Nitric oxide (NO)), neurotoxicity (acetylcholinesterase (AChE)), genotoxicity (comet assay and acridine orange staining (AO)) and histological analysis. In this study, four concentrations 350, 550, 750 and 950 μg/L of ZEA were chosen based on LC10 and LC50 values of the previous report. The results shows that ZEA induces developmental defects like pericardial edema, hyperemia, yolk sac edema, spine curvature and reduction in heart rate from above 550 μg/L exposure and the severity was increased with concentration and time dependent manner. Significant induction in oxidative stress indices (ROS, LPO and NO), reduction in antioxidant defence system (SOD, CAT, GPx, GST and GSH) and changes in metabolic biomarkers (LDH and AP) were observed at higher ZEA exposed concentration. Neurotoxic effects of ZEA were observed with significant inhibition of AChE activity at higher exposure groups (750 and 950 μg/L). Moreover, we also noticed DNA damage, apoptosis and histological changes in the higher ZEA treatments at 96 h post fertilization (hpf) embryos. Hence, in the present study we concluded that oxidative stress is the main culprit in ZEA induced developmental, genotoxicity and neurotoxicity in zebrafish embryos.

PPAR-γ Agonists for the Treatment of Major Depression: A Review.

Introduction: Selective agonists of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ) are used for the treatment of type 2 diabetes. We reviewed their efficacy and safety for the treatment of major depression and the association of their potential antidepressant effects with changes in biomarkers of metabolism and inflammation. Methods: From 8 studies, 4 open-label trials, and 4 randomized controlled trials (RCT) (3 vs. placebo and 1 vs. metformin), 448 patients with major depression were included, of which 209 patients received PPAR-γ agonists (pioglitazone or rosiglitazone) for 6-12 weeks, either alone or in add-on therapy to conventional treatments. Results: PPAR-γ agonists have antidepressant effects in the 4 open-label studies and in 3 out of 4 RCT. No major adverse event was reported. Improvement in depression scores was associated with improvement in 3 biomarkers of insulin resistance (homeostatic model assessment [HOMA-IR], oral glucose tolerance test, and fasting plasma glucose) and 1 biomarker of inflammation (interleukin-6) among 21 biomarkers studied. Conclusion: PPAR-γ agonists may have antidepressant properties, which need to be assessed in further studies of major depressive episodes.

Fructose-containing sugars do not raise blood pressure or uric acid at normal levels of human consumption.

The impact of fructose, commonly consumed with sugars by humans, on blood pressure and uric acid has yet to be defined. A total of 267 weight-stable participants drank sugar-sweetened milk every day for 10 weeks as part of their usual, mixed-nutrient diet. Groups 1 and 2 had 9% estimated caloric intake from fructose or glucose, respectively, added to milk. Groups 3 and 4 had 18% of estimated caloric intake from high fructose corn syrup or sucrose, respectively, added to the milk. Blood pressure and uric acid were determined prior to and after the 10-week intervention. There was no effect of sugar type on either blood pressure or uric acid (interaction P>.05), and a significant time effect for blood pressure was noted (P<.05). The authors conclude that 10 weeks of consumption of fructose at the 50th percentile level, whether consumed as pure fructose or with fructose-glucose-containing sugars, does not promote hyperuricemia or increase blood pressure.

Changes in Adipose Tissue Depots and Metabolic Markers Following a 1-Year Diet and Exercise Intervention in Overweight and Obese Patients With Type 2 Diabetes

OBJECTIVEWe aim to characterize the effects on total body fat and distribution of a 1-year intensive lifestyle intervention (ILI) for weight loss in overweight and obese adults with type 2 diabetes and to examine whether changes in adipose tissue (AT) depots were associated with changes in metabolic biomarkers.RESEARCH DESIGN AND METHODSParticipants were 54 females and 38 males (age 57.8 ± 6.7 years [mean ± SD]; BMI 31.7 ± 3.5 kg/m2) enrolled in the Look AHEAD (Action for Health in Diabetes) trial randomized to ILI or diabetes support and education (DSE) from whom baseline and 1-year MRI measures of total AT (TAT) and regional (arm, trunk, leg) AT, including subcutaneous AT (SAT), visceral AT (VAT), and intermuscular AT (IMAT), were acquired. We tested whether mean changes in ILI and DSE were equal and, within groups, whether changes were different from zero. Regression models tested whether changes in AT compartments were associated with metabolic variable changes.RESULTSBody weight changed −0.52 ± 3.62 kg (P = 0.31) in DSE and −7.24 ± 5.40 kg (P < 0.0001) in ILI. Mean ILI changes were different from DSE (P < 0.001 for TAT, SAT, and IMAT and P < 0.01 for VAT in females). Within ILI, SAT and VAT decreased in males and females (P < 0.0001), but IMAT was unchanged (0.00 ± 0.54 kg; P = 0.99). In DSE, SAT and VAT did not change, but IMAT increased by 0.46 ± 0.55 kg (P < 0.001). Controlling for weight loss, reduction of specific AT depots was associated with improvement in metabolic biomarkers.CONCLUSIONSWeight loss of 7–10% from an ILI over 1 year reduced SAT and VAT and prevented an increase in IMAT. Reductions in AT depots were associated with improvements in biomarkers.

The effects of physical activity on breast cancer survivors after diagnosis.

Adverse health outcomes are often seen in breast cancer survivors due to prolonged treatment with side effects such as loss of energy and lack of physical strength. Physical activity (PA) has been proposed as an adequate intervention for women with breast cancer. Therefore, this review summarizes the effects of physical activity on breast cancer survivors after diagnosis. We searched electronic databases including PubMed, Medline, Embase, and Google Scholar for articles published between January 1980 and May 2013. We included a variety of studies such as randomized controlled trials, pilot studies, and clinical trials. We reviewed these studies for three major outcomes: changes in breast cancer mortality, physiological functions, and metabolic biomarkers. Of 127 studies, 33 studies were selected as eligible studies. These studies included physical activities of varying type, duration, frequency, and intensity (e.g., aerobic and resistance training) and examined changes in three major outcomes among breast cancer survivors. Many of the studies suggest that breast cancer survivors benefit from engaging in physical activity, but some studies were limited in their ability to provide adequate evidence due to relatively small sample sizes, short intervention periods, or high attrition. Based on epidemiological evidence, recent studies demonstrated that those breast cancer survivors who engaged in physical activity significantly lowered their risk of breast cancer mortality and improved their physiological and immune functions. Some studies demonstrated changes in metabolic biomarkers such as insulin and insulin-like growth factors. However, further investigation is required to support these findings because these results are not consistent.

Metabolomics Coupled with Proteomics Advancing Drug Discovery toward More Agile Development of Targeted Combination Therapies

To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.

The influence of salinity on toxicological effects of arsenic in digestive gland of clam Ruditapes philippinarum using metabolomics

Ruditapes philippinarum, a clam that thrives in intertidal zones of various salinities, is a useful biomonitor to marine contaminants. We investigated the influence of dilution to 75% and 50% of normal seawater salinity (31.1) on the responses of the digestive gland of R. philippinarum to arsenic exposure (20 mu g/L), using nuclear magnetic resonance (NMR)-based metabolomics. After acute arsenic exposure for 48 h, salinity-dependent differential metabolic responses were detected. In normal seawater, arsenic exposure increased the concentrations of branched-chain amino acids, and of threonine, proline, phosphocholine and adenosine, and it decreased the levels of alanine, hypotaurine, glucose, glycogen and ATP in the digestive glands. Differential changes in metabolic biomarkers observed at lower salinity (similar to 23.3) included elevation of succinate, taurine and ATP, and depletion of branched-chain amino acids, threonine and glutamine. Unique effects of arsenic at the lowest salinity (similar to 15.6) included down-regulation of glutamate, succinate and ADP, and up-regulation of phosphocholine. We conclude that salinity influences the metabolic responses of this clam to arsenic.

Impact of heavy metals on changes in metabolic biomarkers of carp fish, Cirrhinus mrigala

The Indian Major carp fish, Cirrhinus mrigala were exposed to 1/10 th sub lethal concentration of three toxic heavy metals – Cadmium chloride (CdCl 2 ), Lead chloride (PbCl 2 ) and Mercuric Chloride (HgCl 2 ) for a period of 3, 7, 15, 30 and 45 days to study their effect on biochemical and metabolic enzyme biomarkers. The glycogen contents in gill, liver and muscle tissues of carp fish, Cirrhinus mrigala were found to be decreased. The maximum percentage decrease (65.57%) was observed on day 45 in liver tissue under mercuric chloride toxic stress. The succinate dehydrogenase (SDH), malate dehydrogenase (MDA), cytochrome C-oxidase and protein contents in three tissues were gradually decreased, whereas lactate dehydrogenase (LDH), aspartate amino transferase (AAT) and alanine transferase (AIAT) showed a constant and gradual elevation throughout the experimental period of 45 days under the treatment of heavy metals intoxicated fish. It is observed that the increased / decreased percentage was very much pronounced by HgCl 2 ) in liver tissue in particular. These variations have assumed that the fish yields high energy demands to overcome the stress indicated by the existence of hypoproteinamea in all tissues of fish. // //