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Abstract. Scientists proposed that curcumin could be used for treatment of non-alcoholic fatty liver disease (NAFLD). In this article, we aimed to identify the effect of curcumin on NAFLD improvement. Fifty patients with NAFLD, were divided into two groups in this randomized, double-blind, and controlled clinical trial. Patients in the curcumin group received 250 mg/day of phytosomal curcumin, while those in the control group received 250 mg/day of placebo for duration of eight weeks. Anthropometric measurements and fasting blood samples were taken once at the baseline and once at the end of the study. Analysis was performed on 45 patients (curcumin group n = 22, placebo group n = 22). According to between groups analysis, curcumin significantly reduced the carboxymethyl lisine (CML) (148 ± 108 ng/mL vs 197 ± 101 ng/mL, P = 0.04), 8-hydroxy-2’ -deoxyguanosine (8-OHdG) (46.9 ± 31.1 ng/mL vs 52.1 ± 43.1 ng/mL P = 0.03), liver enzymes (P

Background. Celiac disease (CeD) is an autoimmune intestinal disorder caused by gluten protein consumption in genetically predisposed individuals. As biopsy sampling is an invasive procedure, finding novel noninvasive serological markers for screening of at-risk CeD population is a priority. Metabolomics is helpful in monitoring metabolite changes in body fluids and tissues. In the present study, we evaluated serum metabolite levels of CeD patients relative to healthy controls with the aim of introducing new biomarkers for population screening. Method. We compared the serum metabolic profile of CeD patients ( n = 42 ) and healthy controls ( n = 22 ) using NMR spectroscopy and multivariate analysis. Result. 25 metabolites were identified by serum metabolic profiling. Levels of 3-hydroxyisobutyric acid and isobutyrate showed significant differences in CeD patients’ samples compared with healthy controls ( p < 0.05 ). According to pathway analysis, our data demonstrated that changes in nine metabolic pathways were significantly disrupted/affected in patients with CeD. These enriched pathways are involved in aminoacyl-tRNA biosynthesis; primary bile acid biosynthesis; nitrogen metabolism; glutamine and glutamate metabolism; valine, leucine, and isoleucine biosynthesis and degradation; taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and arginine biosynthesis. Conclusion. In summary, our results demonstrated that changes in the serum level of 25 metabolites may be useful in distinguishing CeD patients from healthy controls, which have the potential to be considered candidate biomarkers of CeD.

Purpose: Non-alcoholic fatty liver disease (NAFLD) is the most preventable type of chronic liver disease worldwide and a risk factor for developing cirrhosis or hepatocellular carcinoma (HCC) if untreated. Although experts have performed lots of efforts to find the underlying mechanisms of NAFLD, it remains a challenge to recognize them. The aim of this study is to distinguish common gene signature and pathways in the human liver during NAFLD progression through the systems biology method.Methods: In this study, the three microarray datasets, GSE48452, GSE63067 and GSE89632, were selected from the NCBI GEO database to explore differentially expressed genes (DEGs) among healthy controls, simple steatosis and non-alcoholic steatohepatitis (NASH) patients. Furthermore, protein-protein interaction (PPI) networks and pathway enrichment analysis were used to detect common genes and biological pathways in different stages of NAFLD.Results: The current study was included 47 healthy subjects, 36 patients with simple steatosis and 46 NASH patients. Common high degree genes among all three sets were CHI3L1, GFBP2, NRG1, PEG10 and FADS2. The top five genes in the hepatic PPI networks of three datasets were STAT3, JUN, CANX, FN1 and MYC. Signal transduction, immune response, and anti-apoptosis were the most important biological pathways between healthy vs. NASH, while cell communication, signal transduction and immune response were three top biological pathways between healthy vs. simple steatosis. Also, the most eminent biological pathways between NASH vs. simple steatosis were metabolism and energy pathways. Conclusion: The present study represented the unique and shared key genes and pathways between different stages of NAFLD, which may facilitate the understanding of the NAFLD mechanism and identify potential therapeutic targets in this disease.

Preeclampsia is a multifactorial disorder defined by hypertension and increased urinary protein excretion during pregnancy. It is a significant cause of maternal and neonatal deaths worldwide. Despite various research efforts to clarify pathogenies of preeclampsia and predict this disease before beginning of symptoms, the pathogenesis of preeclampsia is unclear. Early prediction and diagnosis of women at risk of preeclampsia has not markedly improved. Therefore, the objective of this study was to perform a review on metabolomic articles assessing predictive and diagnostic biomarkers of preeclampsia. Four electronic databases including PubMed/Medline, Web of Science, Sciencedirect, and Scopus were searched to identify studies of preeclampsia in humans using metabolomics from inception to March 2018. Twenty-one articles in a variety of biological specimens and analytical platforms were included in the present review. Metabolite profiles may assist in the diagnosis of preeclampsia and discrimination of its subtypes. Lipids and their related metabolites were the most generally detected metabolites. Although metabolomic biomarkers of preeclampsia are not routinely used, this review suggests that metabolomics has the potential to be developed into a clinical tool for preeclampsia diagnosis and could contribute to an improved understanding of disease mechanisms.PE: preeclampsia; sFlt-1: soluble FMS-like tyrosine kinase-1; PlGF: placental growth factor; GC-MS: gas chromatography-mass spectrometry; LC-MS: liquid chromatography-mass spectrometry; NMR: nuclear magnetic resonance spectroscopy; HMDB: human metabolome database; RCT: randomized control trial; e-PE: early-onset PE; l-PE: late-onset PE; PLS-DA: partial least-squares-discriminant analysis; CRL: crown-rump length; UtPI: uterine artery Doppler pulsatility index; BMI: body mass index; MAP: mean arterial pressure; OS: oxidative stress; PAPPA: plasma protein A; FTIR: Fourier transform infrared; BCAA: branched chain amino acids; Arg: arginine; NO: nitric oxide.

Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid with attractive biological activities. Numerous studies have been conducted on the inflammation-lowering effects of CLA in in vitro and animal models. However, the effects of CLA treatment on the inflammatory markers in humans are controversial. Therefore, the objective of this study was to perform a systematic review and meta-analysis on controlled clinical trials (RCT) assessing the effects of CLA supplementation on the circulating inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The literature search of RCTs was performed using Pubmed/Medline, Scopus, ScienceDirect, Web of science, Cochrane, and Google Scholar databases from inception to March 2017. Weighted mean differences were estimated and the pooled effect size was calculated by a random effects model. Of the 427 identified studies, eleven RCTs, including 420 subjects were included in the statistical analysis. Findings suggested that CLA supplementation increased blood levels of CRP by 0.89 mg/l (95% CI: 0.11, 1.68; P = 0.025) and TNF-α levels by 0.39 pg/ml (95% CI: 0.23, 0.55; P

Background The main causes of the progression of non-alcoholic fatty liver disease (NAFLD) are enhanced levels of reactive oxygen species and lipid peroxidation products. Therefore, the usage of antioxidant agents for the prevention and remedy of this disorder was recommended. Curcumin is proposed to treat NAFLD due to its high antioxidative activity. The aim of this study was to examine the effect of curcumin with piperine supplementation on oxidative stress in subjects with NAFLD. Methods In this double-blind, placebo-controlled trial, 55 subjects were randomly divided into two groups (curcumin with piperine and placebo). The participants received administrations of curcumin (500 mg) in combination with piperine (5 mg) and placebo daily for 8 weeks. Oxidative stress was assessed by measuring serum pro-oxidant and antioxidant balance (PAB) assay before and after the intervention. Results The serum PAB values did not significantly change between the treatment group vs. age and gender-matched placebo group after 8 weeks of supplementation. Also, curcumin in combination with piperine did not show a significant decrease (p = 0.06) in PAB levels compared to baseline. Conclusions The present study demonstrated that a dose of curcumin, co-supplied with piperine might be less than a dose in which curcumin can significantly decrease PAB values in these patients.

Focal segmental glomerulosclerosis (FSGS) is a common glomerulonephritis, and its rates of occurrence are increasing worldwide. Proteinuria is a clinical defining feature of FSGS which correlates with the severity of podocyte injury in patients with nephrotic-range protein excretion. Metabolite biomarkers corresponding with the level of proteinuria could be considered as non-invasive complementary prognostic factors to proteinuria. The urine samples of 15 patients (n = 6 women and n = 9 men) with biopsy-proven FSGS were collected and subjected to nuclear magnetic resonance (NMR) analysis for metabolite profiling. Multivariate statistical analyses, including principal component analysis and orthogonal projection to latent structure discriminant analysis, were applied to construct a predictive model based on patients with proteinuria >3000 mg/day and

Curcumin, a natural polyphenol compound in the spice turmeric, has been found to have potent anti-oxidative and anti-inflammatory activity. Curcumin may treat non-alcoholic fatty liver disease (NAFLD) through its beneficial effects on biomarkers of oxidative stress (OS) and inflammation, which are considered as two feature of this disease. However, the effects of curcumin on NAFLD have been remained poorly understood. This investigation evaluated the effects of administrating curcumin on metabolic status in NAFLD patients. Fifty-eight NAFLD patients participated in a randomized, double-blind, placebo-controlled parallel design of study. The subjects were allocated randomly into two groups, which either received 250 mg phospholipid curcumin or placebo, one capsule per day for a period of 8 weeks. Fasting blood samples were taken from each subject at the start and end of the study period. Subsequently, metabolomics analysis was performed for serum samples using NMR. Compared with the placebo, supplementing phospholipid curcumin resulted in significant decreases in serum including 3- methyl-2-oxovaleric acid, 3-hydroxyisobutyrate, kynurenine, succinate, citrate, α-ketoglutarate, methylamine, trimethylamine, hippurate, indoxyl sulfate, chenodeoxycholic acid, taurocholic acid, and lithocholic acid. This profile of metabolic biomarkers could distinguish effectively NAFLD subjects who were treated with curcumin and placebo groups, achieving value of 0.99 for an area under receiver operating characteristic curve (AUC). Characterizing the serum metabolic profile of the patients with NAFLD at the end of the intervention using NMR-based metabolomics method indicated that the targets of curcumin treatment included some amino acids, TCA cycle, bile acids, and gut microbiota.

Our objective was to perform a systematic review and meta-analysis on randomized controlled trials (RCTs) assessing the effect of green tea on serum adiponectin concentration.We searched PubMed, ISI Web of Science, Scopus, and the Google Scholar databases up to November 2016. RCTs conducted among human adults studied the effects of green tea and green tea extract on serum adiponectin concentrations as an outcome variable was included. The weighted mean differences and standard deviations (SD) of change in serum adiponectin levels were calculated. The random effects model was used for deriving a summary of mean estimates with their corresponding SDs. The protocol was registered with PROSPERO (No. CRD42017057716).Fourteen RCTs were eligible to be included in the systematic review and the meta-analysis. Our analysis showed that green tea did not significantly affect adiponectin concentrations in comparison with placebo (weighted mean difference = -0.02 µg/ml, 95% confidence interval [CI], -0.41, 0.38; p = 0.936). There was a substantial heterogeneity between studies (IGreen tea could not change the circulatory adiponectin levels. The dose and duration of green tea could not change the result. RCTs with longer follow-up periods and higher doses are needed to replicate our results.

Objective The purpose of this study was to conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of green tea on serum leptin and ghrelin concentrations. Methods We searched PubMed, ISI Web of Science, Scopus, and Google scholar databases up to December 2016. The searches included RCTs conducted in human adults, and studies on the effect of green tea and green tea extract on serum leptin and ghrelin concentrations as outcome variables. Weighted mean differences (WMDs) and standard errors (SEs) of changes in serum ghrelin and leptin levels were calculated. The random effects model was used to derive the summary mean estimates with their corresponding SEs. Results Eleven RCTs were eligible to be included in the systematic review and the meta-analysis. Our analysis indicated that green tea did not significantly affect leptin and ghrelin concentrations in comparison to placebo (WMD = 1.28 ng/mL, 95% confidence interval: −0.49 to 3.05; P = 0.156, and WMD = 21.49 pg/mL, 95% confidence interval: −40.86 to 83.84; P = 0.499, respectively). However, green tea was associated with an increase in leptin concentration in studies that lasted for more than 12 wk and an increase in ghrelin in women and non-Asians. Conclusions Green tea or green tea extract might not be able to change circulatory leptin and ghrelin levels, especially with short-term interventions. More RCTs with longer duration of treatment and higher doses are necessary to assess green tea's effect on fat mass and obesity hormones.

Background Increased oxidative stress (OS) and lipid peroxidation may be involved in the pathogenesis of preeclampsia (PE). We conducted a case-control study to evaluate the levels of plasma lipids and trace elements as well as activity of superoxide dismutase (SOD) in PE. Materials and Methods The study consisted of 100 patients who had been diagnosed with PE and 100 normotensive pregnant women who underwent medical checkups that served as the control group. Lipid profile, zinc (Zn) and copper (Cu) levels and SOD activities were measured in the plasma of all subjects. Results Our results showed that the plasma levels of triglycerides and SOD activity were significantly elevated and the levels of Zn and Cu were significantly reduced in patients with PE compared with healthy controls. Increased levels of SOD may indicate antioxidant protective mechanisms against OS in PE-complicated pregnancies. This finding may suggest an involvement of OS in the pathophysiology of PE. Conclusion This study demonstrated a significant negative correlation between SOD activity and levels of trace elements. Furthermore, we suggest that higher triglyceride levels and SOD activity combined with lower Zn and Cu levels may be associated with an increased risk of PE.

Sulfur mustard (SM) is a vesication chemical warfare agent for which there is currently no antidote. Despite years of research, there is no common consensus about the pathophysiological basis of chronic pulmonary disease caused by this chemical warfare agent. In this study, we combined chemometric techniques with nuclear magnetic resonance (NMR) spectroscopy to explore the metabolic profile of sera from SM-exposed patients. A total of 29 serum samples obtained from 17 SM-injured patients, and 12 healthy controls were analyzed by Random Forest. Increased concentrations of seven amino acids, glycerol, dimethylamine, ketone bodies, lactate, acetate, citrulline and creatine together with the decreased very low-density lipoproteins (VLDL) levels were observed in patients compared with control subjects. Our study reveals the metabolic profile of sera from SM-injured patients and indicates that NMR-based methods can distinguish these patients from healthy controls.

Sulfur mustard (SM) is a strong alkylating agent that primarily targets the skin, eye and lung. The current study evaluated the pro-oxidant-antioxidant balance (PAB) assay in human serum of SM-exposed patients.sera of 35 SM-exposed patients and 19 healthy volunteers were recruited. Both groups had nonsmoker and nonalcoholic people with no diseases such as diabetes, heart disease and other pulmonary diseases (COPD because of smoking, asthma and so on). All patients had documented exposure to SM. The PAB was measured.SM-exposed patients with normal values for pulmonary function test and severe obstructive pulmonary disease demonstrated a significant increase in PAB value in compared with healthy volunteers (the PAB values in healthy volunteers, normal and severe patients were 48.74 ± 21.07 HK, 101.45 ± 32.68 HK and 120.23 ± 31.55 HK, respectively). However, the level of oxidation is not related to the severity of disease defined by spirometry findings. A significant negative correlation was established between the PAB value and FEV1.The increased PAB value in chemical casualties showed that these patients are exposed to oxidative stress.

Introduction: Sulfur mustard (SM) is a strong alkylating agent that primarily targets the skin, eye, and lung. Mustard airway is a major late complication of SM exposure. Aims and objectives: Current study evaluated long-term effect of SM on oxidizing and reducing agents values using new method prooxidant-antioxidant balance (PAB) assay in human plasma of SM-injured patients. Methods: sera of 35 SM-exposed patients and 19 healthy controls were recruited. Both groups had nonsmoker and nonalcoholic people with no diseases. The PAB was measured by a new method, recently developed by hamidi, by using 3,3′,5,5′-Tetramethylbenzidine (TMB) and two different kinds of reactions; one enzymatic reaction and a chemical reaction that noted prooxidant– antioxidant balance (PAB) assay. Results: Mean PAB values in control group were 48.74±21.07 HK (Hamidi and Koliakos), PAB levels were 101.45±32.68 HK in SM-exposed patients with normal pulmonary function test and 120.23±31.55 HK in severe obstruction pulmonary disease. . Conclusions: the level of oxidation is not related to the severity of disease defined by spirometry findings and a significant negative correlation was established between the PAB value and FEV 1 . The increased PAB value in chemical casualties showed that these patients are exposed to oxidative stress.Likely, at first cytotoxic levels of SM can directly induce oxidative stress (OS), but many years after exposure the levels of OS were elevated through indirectly effects of inflammatory process.

Introduction: Nuclear magnetic resonance (NMR) spectroscopy is an ideal platform for the metabolic analysis of biofluids. Sulfur mustard (SM) is a alkylating chemical warfare agent that cause lung injury and despite years of research there is no common consensus about the pathophysiological basis of mustard airway disease. Aims and objectives: we used 1H NMR spectroscopy to explore the metabolic profile of sera from mustard airway disease patients. Methods: A total of twenty nine serum samples obtained from SM-injured patients (n=17) and healthy controls (n=12) were investigated. Random forest (RF) analysis was capable of distinguishing SM-exposed patients from controls. Results: A total of 18 metabolites differed significantly in intensity between the two groups. Serum samples from SM-injured patients were characterized by increased concentrations of amino acid metabolism (L-glutamine, L-glutamate, L-asparagine, L-lysine, L-glycine, L-proline, and 4-hydroxyproline), lipid metabolism, citrate, ketone bodies, organic acid (lactate and acetate), urea pathway (citrulline), and creatine, relative to control subjects. Discussion: Our study reveals the metabolic profile of sera from SM-injured patients and indicates that NMR-based methods can distinguish these patients from healthy controls. .Also, serum Metabolomic profile of COPD patients differ with mustard airway disease by increased levels of methylhistidine (a muscle protein) and reduced levels of branched-chain amino acids as well as 4-hydroxyproline and proline. It suggests that Metabolomic-based diagnostics not only can distinguish mustard airway disease with healthy controls, but also can diagnose from COPD.

Chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) are characterized by airway obstruction and an inflammatory process. Reaching early diagnosis and discrimination of subtypes of these respiratory diseases are quite a challenging task than other chronic illnesses. Metabolomics is the study of metabolic pathways and the measurement of unique biochemical molecules generated in a living system. In the last decade, metabolomics has already proved to be useful for the characterization of several pathological conditions and offers promises as a clinical tool. In this article, we review the current state of the metabolomics of COPD, asthma and CF with a focus on the different methods and instrumentation being used for the discovery of biomarkers in research and translation into clinic as diagnostic aids for the choice of patient-specific therapies.

BACKGROUND AND OBJECTIVE: Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of degenerative dementia with progressive loss of cognitive abilities and memory loss. AD is an irreversible, progressive chronic disease that it is the cause of behavior changes and deterioration of thinking ability. Since exact mechanism of neuro-toxicity by beta amyloid has not been identified yet, in this study, the histopathological lesions in CA1 of hippocampus after injection of beta-amyloid in a rat model of AD was studied.METHODS: In this experimental study, 30 adult male Albino Wistar rats weighing (250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups control, sham and BETA-amyloid (ABETA) injection. The lesion was induced by injection of 4µLof ABETA(1-40) into the hippocampal fissure. For behavioral analysis Y-maze and shuttle box were used respectively at the 14 and 16 days post-lesion. For histological studies, Nissl and Bielschowsky staining were done.FINDINGS: The mean scores of alternation behavior for sham, control, and AD group were 80.56%, 86.7%, and 46.2%, respectively. AD group showed a significant reduction in alternation behavior as compared to control and sham group (p