Metabolomics Reveals Novel Serum Metabolic Signatures in Gastric Cancer by a Mass Spectrometry Platform.

Gastric cancer (GAS) is one of the malignant tumors of the gastrointestinal system. Alterations in metabolite composition can reflect pathological processes of GAS and constitute a basis for diagnosis and treatment improvements. In this study, a total of 301 serum samples from 150 GAS patients at different tumor-node-metastasis (TNM) stages and 151 healthy controls were collected. Mass spectrometry platforms were performed to investigate the changes in GAS-related metabolites and explore the new potential serum biomarkers and the metabolic dysregulation associated with GAS progression. Twelve differential metabolites (ethyl 2,4-dimethyl-1,3-dioxolane-2-acetate, D-urobilinogen, 14-HDoHE, 13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid, 5,6-dihydroxyprostaglandin F1a, 9'-carboxy-gamma-tocotrienol, glutaric acid, alanine, tyrosine, C18:2(FFA), adipic acid, and suberic acid) were identified to establish the diagnosis model for GAS. The defined biomarker panel was also statistically significant for GAS progression with different TNM stages. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment revealed the metabolic dysregulation associated with GAS progression. In conclusion, a diagnostic panel was established and validated, which could be used to further stage the early and advanced GAS patients from healthy controls. These findings may provide useful information for explaining the GAS metabolic alterations and try to facilitate the characterization of GAS patients in the early stage.

Causal associations of histidine and 12 site-specific cancers: a bidirectional Mendelian randomization study.

An increasing number of studies indicate that cancer patients' histidine (HIS) circulating levels have changed. However, the causality between HIS and cancer is still not well established. Thus, to ascertain the causal link between HIS and cancers, we performed a bidirectional Mendelian randomization (MR) analysis. Summary-level data are derived from publicly available genome-wide association studies (GWAS). The causal effects were mainly estimated using the inverse-variance weighted method (IVW). The weighted-median (WM) method and MR-Egger regression were conducted as sensitivity analyses. In the forward-MR, we found malignant neoplasm of respiratory system and intrathoracic organs (OR: 1.020; 95% CI: 1.006-1.035; pIVW = 0.007) genetically associated with circulating HIS. And there was no significant genetic correlation between HIS and another 11 site-specific cancers using IVW method. In the reversed-MR, we did not observe the causal relationship between HIS and 12 site-specific cancers. Our findings help clarify that HIS, as a biomarker for malignant neoplasms of respiratory system and intrathoracic organs, is causal rather than a secondary biomarker of the cancerous progression. The mechanism between histidine and cancer progression deserves further investigation.

Dose-response relationships between dairy intake and non-communicable chronic diseases: an NHANES-based cross-sectional study.

The purpose of this study was to explore the possible association between dairy and NCDs and identify possible dairy types that could lower the odds of NCDs. Data were from the 2003-2016 NHANES, a cross-sectional study with 20,297 adults. Multivariable logistic regression analyses and restricted cubic spline (RCS) models were conducted. In the highest intake group (>250 g/d, 1 daily serving), yogurt and milk were inversely associated with the odds of general obesity and central obesity [OR (95% CI), general obesity, 0.74 (0.60-0.91) and 0.75 (0.68-0.83); central obesity, 0.70 (0.56-0.87), and 0.77 (0.70-0.86), respectively, p < 0.05]. Higher milk intake is inversely associated with diabetes, and higher cream intake is associated with a lower likelihood of hyperlipidaemia. The intake of yogurt, milk, cheese, and butter was 0-308 g/d (0-1.2 daily servings), 0-887 g/d (0-3.5 daily servings), <75 g/d (1.7 daily servings), and <15 g/d (0.5 daily servings), respectively.

Dietary isoflavones intake is inversely associated with non-alcoholic fatty liver disease, hyperlipidaemia and hypertension.

This study investigated associations between total isoflavones and their categories (daidzein, genistein, glycitein) intake and the risks for metabolic disorders. We used the data of 6786 Chinese adults from the Nutrition Health Atlas Project. We performed multiple logistic regression and restricted cubic spline models assessing the risks for metabolic disorders (non-alcoholic fatty liver disease (NAFLD), hyperlipidaemia, hypertension, diabetes and overweight/obesity) in each category of isoflavones. Higher total isoflavones, daidzein and genistein intake were inversely associated with NAFLD (p < .05). Higher total isoflavones, daidzein, genistein and glycitein intake were also inversely associated with hyperlipidaemia (p < .01) and hypertension (p < .01). Dose-response analyses revealed that total isoflavones, daidzein, genistein and glycitein intakes were associated with the risks of metabolic disorders in a nonlinear trend. In conclusion, total isoflavones, daidzein and genistein intake were inversely associated with NAFLD, hyperlipidaemia and hypertension. Glycitein was inversely associated with hyperlipidaemia and hypertension.

EWASdb: epigenome-wide association study database.

DNA methylation, the most intensively studied epigenetic modification, plays an important role in understanding the molecular basis of diseases. Furthermore, epigenome-wide association study (EWAS) provides a systematic approach to identify epigenetic variants underlying common diseases/phenotypes. However, there is no comprehensive database to archive the results of EWASs. To fill this gap, we developed the EWASdb, which is a part of 'The EWAS Project', to store the epigenetic association results of DNA methylation from EWASs. In its current version (v 1.0, up to July 2018), the EWASdb has curated 1319 EWASs associated with 302 diseases/phenotypes. There are three types of EWAS results curated in this database: (i) EWAS for single marker; (ii) EWAS for KEGG pathway and (iii) EWAS for GO (Gene Ontology) category. As the first comprehensive EWAS database, EWASdb has been searched or downloaded by researchers from 43 countries to date. We believe that EWASdb will become a valuable resource and significantly contribute to the epigenetic research of diseases/phenotypes and have potential clinical applications. EWASdb is freely available at http://www.ewas.org.cn/ewasdb or http://www.bioapp.org/ewasdb.

Lipid profile and risk of ovarian tumours: a meta-analysis.

BACKGROUND: Existing data from several reports on the association between lipid profile and ovarian tumour (OT) suggests divergent conclusions. Our aim was to examine whether circulating lipid profile: total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) differed between cases and non-cases of OT. METHODS: Electronic repositories; PUBMED, EMBASE and Cochrane library were explored through December 2019 to retrieve published articles for inclusion in the meta-analysis after quality assessment. Heterogeneity was assessed using I2 statistics, the effect of individual studies on the overall effect size was tested using sensitivity analysis and funnel plot was used to evaluate publication bias. RESULTS: Twelve studies, involving 1767 OT cases and 229,167 non-cases of OT were included in this meta-analysis and I2 statistics ranged between 97 and 99%. Mean circulating TC (- 16.60 [- 32.43, - 0.77]mg/dL; P = 0.04) and HDL (- 0.25[- 0.43, - 0.08]mmol/L; P = 0.005) were significantly lower among OT cases compared to non-OT cases. CONCLUSION: Decreased TC and HDL profiles were observed among subjects with OT in this collection of reports. The implications of TC and HDL in tumour manifestations and growth need to be validated in a large multi-ethnic longitudinal cohort adjusting for relevant confounders.

Association between dairy consumption and prevalence of obesity in adult population of northeast China: An internet-based cross-sectional study.

BACKGROUND AND OBJECTIVES: Dairy has been shown to reduce the risk of obesity in many epidemiological studies. However, few studies have been fully conducted in China in this respect. We aimed to investigate the association between dairy consumption and prevalence of obesity in an adult Chinese population. METHODS AND STUDY DESIGN: A cross-sectional study was performed in an adult population of 5598 in northeast China, aged ≥18. Intakes of dairy products were obtained by internet-based dietary questionnaire for the Chinese (IDQC). The associations between total and individual dairy consumption and prevalence of overall and abdominal obesity were examined by logistic regression. Sex stratification was performed. RESULTS: A total of 3871 participants, including 1700 men and 2171 women, were eligible for analysis. Men who consumed ≥100 g/day of yogurt had lower risks of abdominal obesity (multivariate-adjusted OR=0.41; 95% CI: 0.24-0.70) than men who did not consume yogurt. Women who consumed ≥200 g/day of milk had lower risks of overall obesity (multivariate-adjusted OR=0.47; 95% CI: 0.24-0.91) than women who did not consume milk. CONCLUSIONS: Increased dairy consumption was associated with lower risk of obesity in adult population in northeast China. Further studies are needed to confirm these observational findings and explain the observed gender-specific difference.

EWAS: epigenome-wide association study software 2.0.

Motivation: With the development of biotechnology, DNA methylation data showed exponential growth. Epigenome-wide association study (EWAS) provide a systematic approach to uncovering epigenetic variants underlying common diseases/phenotypes. But the EWAS software has lagged behind compared with genome-wide association study (GWAS). To meet the requirements of users, we developed a convenient and useful software, EWAS2.0. Results: EWAS2.0 can analyze EWAS data and identify the association between epigenetic variations and disease/phenotype. On the basis of EWAS1.0, we have added more distinctive features. EWAS2.0 software was developed based on our 'population epigenetic framework' and can perform: (i) epigenome-wide single marker association study; (ii) epigenome-wide methylation haplotype (meplotype) association study and (iii) epigenome-wide association meta-analysis. Users can use EWAS2.0 to execute chi-square test, t-test, linear regression analysis, logistic regression analysis, identify the association between epi-alleles, identify the methylation disequilibrium (MD) blocks, calculate the MD coefficient, the frequency of meplotype and Pearson's correlation coefficients and carry out meta-analysis and so on. Finally, we expect EWAS2.0 to become a popular software and be widely used in epigenome-wide associated studies in the future. Availability and implementation: The EWAS software is freely available at http://www.ewas.org.cn or http://www.bioapp.org/ewas.

Higher intakes of energy-adjusted dietary amino acids are inversely associated with obesity risk.

We assessed the relationship between energy-adjusted amino acids (EAA) intakes and obesity risk using data on nutrient intakes derived from the Chinese food composition tables to determine dietary intakes (DI) among 1109 obese and 3009 normal weight subjects. Dietary patterns (DP) were identified using principal component analysis, multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) of obesity risk by quartiles of EAA intakes was estimated using logistic regression with two-sided P < 0.05. Multivariable-adjusted OR and 95% CI for obesity risk were 1.00, 0.801 (0.573, 1.119), 0.718 (0.504, 1.024) and 0.532 (0.353, 0.803) P-trend = 0.003 across energy-adjusted quartiles of total AA intakes. Similarly, higher DI of 13 AA; isoleucine, leucine, valine, lysine, cysteine, phenylalanine, tyrosine, threonine, histidine, aspartic acid, glutamic acid, proline, and serine were associated with lower risk of obesity. Furthermore, six DP; 'Wheaten food and Rice', 'Fruit, Vegetables and Milk', 'Snack, Beverage and Ice cream', 'Potatoes, Soybean & Egg', 'Livestock & Poultry meat' and 'Fish' were identified. Multivariable-adjusted OR and 95% CI across quartiles of DP adherence for obesity risk were 1.00, 0.737 (0.535, 1.017), 0.563 (0.406, 0.779), 0.724 (0.518, 1.011) P-trend = 0.018 for 'Fruit, Vegetables and Milk', 1.00, 0.734 (0.531, 1.013), 0.841(0.609, 1.161), 0.657 (0.478, 0.904) P-trend = 0.027 for 'Potatoes, Soybean & Egg' and 1.00, 1.106 (0.791, 1.548), 1.367(0.975, 1.917), 1.953 (1.399, 2.726) P-trend = 0.000 for 'Fish'. Additionally, lower adherence to 'Snack, Beverage and Ice cream' and 'Fish' patterns is associated with a protective higher AA intake-obesity risk relationship. Energy-adjusted AA intakes were inversely associated with obesity risk, but the associations appear modifiable by DP adherence of respondents.

Both WHR and FLI as Better Algorithms for Both Lean and Overweight/Obese NAFLD in a Chinese Population.

GOALS: To compare current nonalcoholic fatty liver disease (NAFLD)-related algorithms to find suitable algorithms for NAFLD, especially lean NAFLD in middle-aged and elderly Chinese population. BACKGROUND: NAFLD is the most common cause of chronic liver disease in the world today. Various algorithms based on obesity indicators, blood lipids, and liver enzymes, etc. have been developed to screen NAFLD. MATERIALS AND METHODS: General, anthropometric and biochemical characteristics were collected. One-way analysis of variance and the χ test were applied to test the differences in continuous and categorical variables, respectively. Multivariable logistic regression analyses, adjusted by age, gender, body mass index, tobacco use, alcohol consumption, and physical activities, were used to investigate the associations between NAFLD-related algorithms and NAFLD. The accuracy and cut-off point of NAFLD-related algorithms to detect NAFLD were evaluated by area under the receiver operator characteristic curve and the maximum Youden index analysis, respectively. RESULTS: In 8 NAFLD-related algorithms, the receiver operator characteristic of fatty liver index (FLI) and waist circumstance-to-height ratio (WHR) for NAFLD were in the whole (0.83 and 0.84), lean (0.74 and 0.74), and overweight/obese (0.71 and 0.72) population, respectively, which were higher than those of other algorithms. The cut-off points of WHR and FLI for NAFLD were different in the overall (0.50 and 20), lean (0.47 and 10), and overweight/obese (0.53 and 45) population. CONCLUSIONS: WHR and FLI could be the most accurate of 8 algorithms for the noninvasive diagnosis of NAFLD in both lean and overweight/obese population.

Lean non-alcoholic fatty liver disease patients had comparable total caloric, carbohydrate, protein, fat, iron, sleep duration and overtime work as obese non-alcoholic fatty liver disease patients.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease that involves a complex interaction between genetics, diet, and lifestyle. Although closely related with obese subjects, it is also common in lean humans. This study aimed to characterize the diet and lifestyle of lean and obese NAFLD patients in China. METHODS: To characterize the diet and lifestyle of lean and obese NAFLD patients, we conducted a matched case-control study that included 351 Chinese adults. General characteristics, dietary intake, and lifestyle were gathered by using a valid and reliable dietary questionnaire. We compared the dietary intake and lifestyle between lean and obese NAFLD patients. RESULTS: All NAFLD patients had more total caloric, calorigenic nutrients (carbohydrate, fat, and protein), grain, potato, fruit, and iron with higher levels of waist circumference and overtime work but shorter sleep duration than their corresponding controls. Particularly, lean NAFLD patients consumed comparable total caloric, calorigenic nutrients, iron, sleep duration, and overtime work as obese NAFLD patients, though they consumed lower levels of grain, potato, and fruit (lean NAFLD patients vs. obese NAFLD patients: mean ± SD, g/day grain: 291.8 ± 83.8, 365.2 ± 89.0; potato: 63.5 ± 33.1, 80.4 ± 37.6; fruit: 324.3 ± 148.4, 414.0 ± 220.4; P < 0.0001). CONCLUSION: Non-alcoholic fatty liver disease patients had higher total caloric, calorigenic nutrients, grain, potato, fruit, iron, and overtime work but shorter sleep duration. Lean NAFLD patients had comparable total caloric, calorigenic nutrients, iron, sleep duration, and overtime work as obese NAFLD patients. These features could be used to the nutritional education and therapeutic guidance for lean NAFLD patients in the future.

Increasing extracellular Ca2+ sensitizes TNF-alpha-induced vascular cell adhesion molecule-1 (VCAM-1) via a TRPC1/ERK1/2/NFκB-dependent pathway in human vascular endothelial cells.

Increasing circulating Ca2+ levels within the normal range has been reported to positively correlate with the incidence of fatal cardiovascular diseases (CVDs). However, limited studies have been able to delineate the potential mechanism(s) linking circulating Ca2+ to CVD. In this study, we exposed primary human umbilical vein endothelial cells (HUVECs) and human umbilical vein cell line (EA.hy926) to different extracellular Ca2+ to mimic the physiological state. Our data revealed that increasing extracellular Ca2+ significantly enhanced susceptibility to tumor necrosis factor (TNF)-alpha-stimulated vascular cell adhesion molecule (VCAM)-1 expression and monocytes adhesion. Knocking-down VCAM-1 by siRNA abolished calcium-induced monocytes adhesion on HUVECs. Follow up mechanistic investigations identified that extracellular Ca2+-increased calcium influx contributed to the activation of VCAM-1. This was mediated via upregulation of transient receptor potential channel (TRPC)1 in a nuclear factor (NF)κB-dependent manner. Most importantly, we found that a novel TRPC1-regulated extracellular signal-regulated kinase 1/2 (ERK1/2) pathway exclusively contributed to calcium-induced NFκB activation. This study provided direct evidence that increasing extracellular Ca2+ enhanced TNF-alpha-induced VCAM-1 activation and monocytes adhesion. Moreover, we identified a novel TRPC1/ERK1/2/NFκB signaling pathway mediating VCAM-1 activation and monocyte adhesion in this pathological process. Our studies indicate that blood calcium levels should be strictly monitored to help prevent CVD, and that TRPC1 might act as a potential target for the treatment and prevention against increased circulating calcium-enhanced CVDs.

Associations of dietary phytosterols with blood lipid profiles and prevalence of obesity in Chinese adults, a cross-sectional study.

BACKGROUND: It has been established in RCTs that high dose of phytosterols can significantly reduce blood cholesterol. However, it was uncertain whether low dose of phytosterols from daily diets was effective. In this study, we evaluated the associations between dietary phytosterols and body mass index (BMI), waist circumference (WC), blood glucose, serum lipid profiles and prevalence of overweight/obesity and abdominal obesity in healthy subjects. METHODS: Four hundred nine men and 503 women aged 18-60 years were included in this study. Dietary intakes of phytosterols were estimated using a validated food frequency questionnaire. Height, body weight, WC and blood pressure were measured, an oral glucose tolerance test was performed. Moreover, fasting serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDLc) and low density lipoprotein cholesterol (LDLc) were further determined. RESULTS: When comparing extreme quartiles of dietary phytosterols, significant differences of BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum TC and LDLc were found. Dietary phytosterols presented a negative association with BMI, WC, SBP, DBP, serum TC and LDLc (with and without adjustment for energy). After adjustment for confounders, we found higher dietary phytosterols were linked with lower prevalence of overweight/obesity (OR highest vs. lowest quartile = 0.487; 95% CI 0.234, 0.918 for men; OR highest vs. lowest quartile = 0.277; 95% CI 0.124, 0.619 for women) and abdominal obesity (OR highest vs. lowest quartile = 0.344; 95% CI 0.144, 0.819 for men; OR highest vs. lowest quartile = 0.321; 95% CI 0.140, 0.571 for women). CONCLUSIONS: Higher dietary phytosterols were associated with lower BMI, WC, blood pressure, serum TC and LDLc and lower prevalence of overweight/obesity and abdominal obesity in Chinese adults.

Dietary Sulfur-Containing Amino Acids Are Associated with Higher Prevalence of Overweight/Obesity in Northern Chinese Adults, an Internet-Based Cross-Sectional Study.

BACKGROUND/AIMS: Elevation of plasma sulfur-containing amino acids (SAAs) is generally associated with higher body mass index (BMI) and unfavorable lipid profiles. It is not known how dietary SAAs relate to these associations in humans. METHODS: A convenient tool named internet-based dietary questionnaire for Chinese (IDQC) was used to estimate dietary SAAs intake. A total of 936 participants were randomly recruited and asked to complete the IDQC. Furthermore, 90 subjects were randomly selected to perform a subgroup study. The associations between dietary SAAs and prevalence of obesity, lipid profiles, and status of insulin resistance (IR), inflammation and oxidative stress were assessed. RESULTS: Dietary total SAAs and cysteine of overweight/obese participants were significantly higher. Dietary total SAAs and cysteine were positively associated with BMI and waist circumference. Higher dietary total SAAs were associated with higher prevalence of overweight/obesity. Higher dietary total SAAs and cysteine also associated with higher serum triglyceride (total cholesterol), low density lipoprotein, fasting blood glucose, 2 h-postprandial glucose, and homeostasis model assessment of IR. In the subgroup study, positive associations between dietary SAAs and inflammation biomarkers were also observed. CONCLUSIONS: Dietary SAAs are associated with higher prevalence of overweight/obesity, unfavorable lipid profiles and status of IR, and inflammation.

Effects of Histidine Supplementation on Global Serum and Urine 1H NMR-based Metabolomics and Serum Amino Acid Profiles in Obese Women from a Randomized Controlled Study.

The aim of current study was to investigate the metabolic changes associated with histidine supplementation in serum and urine metabolic signatures and serum amino acid (AA) profiles. Serum and urine 1H NMR-based metabolomics and serum AA profiles were employed in 32 and 37 obese women with metabolic syndrome (MetS) intervened with placebo or histidine for 12 weeks. Multivariable statistical analysis were conducted to define characteristic metabolites. In serum 1H NMR metabolic profiles, increases in histidine, glutamine, aspartate, glycine, choline, and trimethylamine-N-oxide (TMAO) were observed; meanwhile, decreases in cholesterol, triglycerides, fatty acids and unsaturated lipids, acetone, and α/ß-glucose were exhibited after histidine supplement. In urine 1H NMR metabolic profiles, citrate, creatinine/creatine, methylguanidine, and betaine + TMAO were higher, while hippurate was lower in histidine supplement group. In serum AA profiles, 10 AAs changed after histidine supplementation, including increased histidine, glycine, alanine, lysine, asparagine, and tyrosine and decreased leucine, isoleucine, ornithine, and citrulline. The study showed a systemic metabolic response in serum and urine metabolomics and AA profiles to histidine supplementation, showing significantly changed metabolism in AAs, lipid, and glucose in obese women with MetS.

Free fatty acids profile among lean, overweight and obese non-alcoholic fatty liver disease patients: a case - control study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) given its association with obesity and diabetes may perhaps exert distinct free fatty acids (FFA) pattern, but the understanding of this phenomenon is limited. To this effect, we evaluated FFA profiles among healthy subjects and NAFLD patients stratified by body weight, to identify FFA valuable for early diagnosis of NAFLD. METHODS: Serum FFA profiles of healthy and NAFLD (lean, overweight and obese) subjects was determined using gas chromatography-mass spectrometry (GC-MS) and distinctions in FFA patterns were evaluated using one-way ANOVA while Receiver operating characteristics (ROC) and logistic regression models were used to explore FFA significant for diagnosing NAFLD. RESULTS: NAFLD patients presented significantly higher (P < 0.05) serum FFA profiles compared to healthy controls (HC). While total FFA profiles were insignificantly different between lean (2093.33 ± 558.11 µg/ml) and overweight (2420.81 ± 555.18 µg/ml) NAFLD patients, obese NAFLD (2739.01 ± 810.35 µg/ml) presented most significantly elevated (P < 0.05) total FFA profiles compared with HC. Of the four FFA; myristic acid (14:0), palmitoleic acid (16:1), γ-linolenic acid (γ-18:3) and cis-7,10,13,16,19-docosapentaenoic acid (22:5), selected in ROC analysis given their high Youden's index and AUC, only 14:0; 5.58(1.37, 22.76) and 16:1; 4.36(1.34, 14.13) had statistical significant odd ratios. CONCLUSION: Our findings suggest 14:0 and 16:1 are promising for early diagnosis of NAFLD.

Effects of tea or tea extract on metabolic profiles in patients with type 2 diabetes mellitus: a meta-analysis of ten randomized controlled trials.

As consumption of tea has been confirmed as a protective factor for type 2 diabetes mellitus (T2DM), it would be interesting to know if T2DM patients could benefit from tea. Because of small sample sizes and inconsistent results of previous studies, we performed this meta-analysis to reevaluate the effects of tea or tea extract on all available outcomes in patients with T2DM. We systematically searched electronic databases of PubMed, Cochrane Library and EMBASE to identify randomized controlled trials of tea in T2DM patients up to January 2015. Weight mean differences for the changes in all outcomes were pooled by Review Manager 5.2 (Cochrane Collaboration, Oxford, England). A total of ten trials including 608 subjects were identified. The meta-analysis found that tea could alleviate the decrease of fasting blood insulin [1.30 U/L, 95% CI (0.36, 2.24)], and reduced waist circumference only in more than 8-week intervention [-2.70 cm, 95% CI (-4.72, -0.69)], whereas there were no statistically significant differences with regard to homeostasis model of insulin resistance 0.38 (-0.18, 0.95), fasting blood glucose -0.05 mmol/L (-0.51, 0.40), low density lipoprotein-cholesterol 0.07 mmol/L (-0.15, 0.29), high density lipoprotein-cholesterol 0.01 mmol/L (-0.08, 0.09), body mass index -0.15 kg/m(2) (-0.50, 0.21), SBP 0.35 mmHg (-3.54, 4.24), DBP -1.02 mmHg (-3.53, 1.48), triglycerides -0.11 mmol/L (-0.28, 0.05) and fasting cholesterol -0.05 mmol/L (-0.20, 0.11) in patients with T2DM, and leptin, ADPN, CRE and UA were also non-significant. The intervention of tea or tea extraction could maintain a stable fasting blood insulin and reduce waist circumference in the T2DM patients; however, the effects on other outcomes were not significant. Copyright © 2015 John Wiley & Sons, Ltd.

Pathway analysis of genome-wide association study and transcriptome data highlights new biological pathways in colorectal cancer.

Colorectal cancer (CRC) is a common malignancy that meets the definition of a complex disease. Genome-wide association study (GWAS) has identified several loci of weak predictive value in CRC, however, these do not fully explain the occurrence risk. Recently, gene set analysis has allowed enhanced interpretation of GWAS data in CRC, identifying a number of metabolic pathways as important for disease pathogenesis. Whether there are other important pathways involved in CRC, however, remains unclear. We present a systems analysis of KEGG pathways in CRC using (1) a human CRC GWAS dataset and (2) a human whole transcriptome CRC case-control expression dataset. Analysis of the GWAS dataset revealed significantly enriched KEGG pathways related to metabolism, immune system and diseases, cellular processes, environmental information processing, genetic information processing, and neurodegenerative diseases. Altered gene expression was confirmed in these pathways using the transcriptome dataset. Taken together, these findings not only confirm previous work in this area, but also highlight new biological pathways whose deregulation is critical for CRC. These results contribute to our understanding of disease-causing mechanisms and will prove useful for future genetic and functional studies in CRC.

CLU rs2279590 polymorphism contributes to Alzheimer's disease susceptibility in Caucasian and Asian populations.

It is reported that CLU rs2279590 polymorphism is significantly associated with Alzheimer's disease (AD) in European ancestry. Recent studies investigated rs2279590 polymorphism in Asian population (Chinese, Japanese and Korean). Four studies showed negative association and two studies showed weak association between rs2279590 and AD. We believe that the weak association or no association may be caused by the relatively small sample size in Asian population. Here, we reinvestigated the association in Asian population. Meanwhile, to investigate the genetic heterogeneity of the rs2279590 polymorphism in Asian and Caucasian populations, we searched the PubMed and AlzGene databases and selected 11 independent studies (6 studies in Asian population and 5 studies in Caucasian population) including 20,655 individuals (8,605 cases and 12,050 controls) for meta-analysis. Our results showed significant association between rs2279590 polymorphism and AD in Asian population with P = 2.00E-04 and P = 2.00E-04 using additive and recessive models, respectively. We observed no significant heterogeneity between Asian and Caucasian populations. We believe that our results may be helpful to understand the mechanisms of CLU in AD pathogenesis and will be useful for future genetic studies in AD.

Histidine supplementation alleviates inflammation in the adipose tissue of high-fat diet-induced obese rats via the NF-κB- and PPARγ-involved pathways.

Obesity is considered to be accompanied by a chronic low-grade inflammatory state that contributes to the occurrence of many chronic diseases. Our previous study has demonstrated that histidine supplementation significantly ameliorates inflammation and oxidative stress in obese women. However, the in vivo potential mechanisms are not known. The present study was conducted to investigate the mechanisms underlying the effects of histidine on inflammation in a high-fat diet (HFD)-induced female obese rat model. An obese model was established in female Sprague-Dawley rats by HFD feeding for 8 weeks and followed by histidine supplementation for another 4 weeks. The results revealed that HFD-increased body weight and HFD-lowered serum histidine concentrations were significantly reversed by histidine supplementation (P< 0·05). In addition, the serum concentrations of TNF-α, IL-6, C-reactive protein (CRP) and malondialdehyde were significantly reduced and those of superoxide dismutase (SOD) were significantly increased by histidine supplementation when compared with those in obese rats (P< 0·05). Correspondingly, the mRNA expressions of TNF-α, IL-6 and CRP in the adipose tissue were significantly down-regulated and that of CuZnSOD was significantly up-regulated by histidine supplementation (P< 0·05). Histidine supplementation significantly reduced the HFD-induced translocation of NF-κB p65 into the nucleus (P= 0·032) by reducing the phosphorylation of the inhibitor of κBα in the adipose tissue. The results also revealed that the expression of adiponectin was markedly increased both in the serum and in the adipose tissue after histidine supplementation, accompanied by the activation of PPARγ (P= 0·021). These findings indicate that histidine is an effective candidate for ameliorating inflammation and oxidative stress in obese individuals via the NF-κB- and PPARγ-involved pathways.