Yihua Wu

Aspirin use after diagnosis but not prediagnosis improves established colorectal cancer survival: a meta-analysis

Objective The objective of this meta-analysis was to systematically assess the survival benefit of aspirin use before or after diagnosis for patients with colorectal cancer (CRC). Design Relevant studies were identified through searching PubMed, Embase and Cochrane databases before May 2014. Two investigators extracted data independently for baseline characteristics and outcomes from the included studies. Either a fixed-effects or a random-effects model was derived to composite the pooled HR for overall mortality and CRC-specific mortality of CRC. Results Seven studies on postdiagnosis aspirin therapy and seven studies on prediagnosis aspirin use were finally included in this meta-analysis. The overall survival benefit associated with postdiagnosis aspirin use represented an HR of 0.84 (95% CI 0.75 to 0.94). This effect was observed both in colon cancer (HR=0.78, 95% CI 0.64 to 0.96) and in rectal cancer (HR=0.90, 95% CI 0.83 to 0.98). Besides, the survival benefit of postdiagnosis aspirin use appeared to be confined to those patients with positive prostaglandin endoperoxide synthase 2 (PTGS2, also known as cyclooxygenase-2, COX-2) expression (HR=0.65, 95% CI 0.50 to 0.85) and with mutated PIK3CA tumours (HR=0.58, 95% CI 0.37 to 0.90). Aspirin use postdiagnosis was not associated with CRC-specific mortality (HR=0.77, 95% CI 0.52 to 1.14). We observed no evidence of an association between prediagnosis aspirin use and CRC overall mortality (HR=1.01, 95% CI 0.96 to 1.06) or CRC-specific mortality (HR=0.93, 95% CI 0.82 to 1.05). Conclusions These findings provide further indication that postdiagnosis aspirin therapy improved CRC overall survival, especially for patients with positive PTGS2 (COX-2) expression and mutated PIK3CA tumours.

Effects of dietary supplementation of methionine and lysine on milk production and nitrogen utilization in dairy cows.

The effect of the content of lysine and methionine in metabolizable protein (MP) on lactation performance and N utilization in Chinese Holstein cows was determined. A control diet (C) was formulated to be adequate in energy but slightly limiting in MP. The concentration of Met and Lys in MP was 1.87 and 5.93%, respectively. The treatments were as follows (% of Met or Lys in MP): L=diet C supplemented with L-lysine-HCl at 0.49% on a dry matter (DM) basis (Met, 1.87; Lys, 7.00); M=diet C supplemented with 2-hydroxy-4-(methylthio)-butanoic acid (HMB) at 0.15% (Met, 2.35; Lys, 5.93); ML=diet C supplemented with 0.49% L-lysine HCl and 0.15% HMB (Met, 2.39; Lys, 7.10). The diets were fed to 60 Chinese Holsteins in mid-lactation (average days in milk=120, and milk yield=32.0 kg/d) for 8 wk. Milk yield was increased by supplementation of either Lys (1.5 kg/d) or Met (2.0 kg/d), and supplementation of both Lys and Met further increased milk yield (3.8 kg/d). There was no significant difference in dry matter intake across treatment groups. Cows on treatments M (3.95%) and ML (3.90%) had higher milk fat content than those on C (3.60%) and L (3.67%), but there were no significant differences in milk protein and lactose contents or somatic cell count among treatments. Supplementation of Met or Lys significantly increased Met or Lys concentration in arterial plasma. Treatment ML had a higher conversion of intake N to milk N and lower urea N concentrations in serum, urine, and milk than did treatment C. Supplementing HMB and L-lysine-HCl to provide approximately 2.3% Met and 7.0% Lys of the MP in diets slightly limiting in MP increased milk production, milk protein yield, and N utilization efficiency.

Association between dietary fiber intake and risk of coronary heart disease: A meta-analysis

BACKGROUND & AIMS The association between coronary heart disease (CHD) and dietary fiber intake is not consistent, especially for the subtypes of dietary fiber. The aim of our study was to conduct a meta-analysis of existing cohort published studies assessing the association between dietary fiber intake and risk of CHD, and quantitatively estimating their dose-response relationships. METHODS We searched PubMed and EMBASE before May 2013. Random-effect model was used to calculate the pool relative risk (RRs) for the incidence and mortality of CHD. Dose-response, subgroup analyses based on fiber subtypes, heterogeneity and publication bias were also carried out. RESULTS Eighteen studies involving 672,408 individuals were finally included in the present study. The pooled-adjusted RRs of coronary heart disease for the highest versus lowest category of fiber intake were 0.93 (95% confidence interval (CI), 0.91-0.96, P < 0.001) for incidence of all coronary events and 0.83 (95% CI, 0.76-0.91, P < 0.001) for mortality. Further subgroup analyses based on fiber subtypes (cereal, fruit, and vegetable fiber), indicated that RRs were 0.92 (95% CI, 0.85-0.99, P = 0.032), 0.92 (95% CI, 0.86-0.98, P = 0.01), 0.95 (95% CI, 0.89-1.01, P = 0.098) respectively for all coronary event and 0.81 (95% CI, 0.72-0.92, P = 0.001), 0.68 (95% CI, 0.43-1.07, P = 0.094), 0.91 (95% CI, 0.74-1.12, P = 0.383) for mortality. In addition, a significant dose-response relationship was observed between fiber intake and the incidence and mortality of CHD (P < 0.001). CONCLUSIONS Our results indicate that consumption of dietary fiber is inversely associated with risk of coronary heart disease, especially for fiber from cereals and fruits. Besides, soluble and insoluble fibers have the similar effect. A significant dose-response relationship is also observed between fiber intake and CHD risk.

MiR-22 regulates 5-FU sensitivity by inhibiting autophagy and promoting apoptosis in colorectal cancer cells

Autophagy has become one of the most important mechanisms of chemotherapy resistance by supporting the survival of tumor cells under metabolic and therapeutic stress. Here, we showed that miR-22 inhibited autophagy and promoted apoptosis to increase the sensitivity of colorectal cancer (CRC) cells to 5-fluorouracil (5-FU) treatment both in vitro and in vivo. B-cell translocation gene 1 (BTG1) was identified as a new target of miR-22, which could reverse the inhibition of autophagy induced by miR-22. Thus, miR-22 may function as an important switch between autophagy and apoptosis to regulate 5-FU sensitivity through post-transcriptional silencing of BTG1. Promisingly, miR-22 could be considered as both a predictor of 5-FU sensitivity for personalized treatment and a therapeutic target for colorectal cancer.

Diagnostic value of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography for the detection of metastases in non-small-cell lung cancer patients

In the recent years, fluorine 18 fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET)/computed tomography (CT) has emerged as a new modality for staging non–small‐cell lung cancer (NSCLC) patients. The aim of this meta‐analysis was to assess the diagnostic value of 18F‐FDG PET/CT in detecting metastatic lesions in NSCLC patients. Meta‐analysis methods were used to pool sensitivity, specificity, positive and negative likehood ratios, diagnostic odd ratios and to construct a summary receiver‐operating characteristic curve. Data from included studies were pooled to compare the diagnostic accuracy between PET/CT and PET or CT alone in nodal staging. Totally, 56 studies involving 8,699 patients met the inclusion criteria. The pooled sensitivities and specificities of 18F‐FDG PET/CT were 0.72 [95% confidence interval (CI): 0.65–0.78] and 0.91 (95% CI: 0.86–0.94) in determining mediastinal nodal staging; 0.71 (95% CI: 0.60–0.80) and 0.83 (95% CI: 0.77–0.88) in intrathoracic staging; 0.78 (95% CI: 0.64–0.87) and 0.90 (95% CI: 0.84–0.94) in intrathoracic staging on a per‐node basis. For detecting extrathoracic metastases, the pooled sensitivities and specificities of 18F‐FDG PET/CT were 0.77 (95% CI: 0.47–0.93) and 0.95 (95% CI: 0.92–0.97) for all extrathoracic metastases; 0.91 (95% CI: 0.80–0.97) and 0.98 (95% CI: 0.94–0.99) for bone metastases. 18F‐FDG PET/CT is beneficial in detecting lymph node metastases and extrathoracic metastases although PET/CT showed low sensitivity in detecting brain metastases. 18F‐FDG PET/CT confers significantly higher sensitivity and specificity than contrast‐enhanced CT (both p < 0.01) and higher sensitivity than 18F‐FDG PET in staging NSCLC (p < 0.05).

Long non-coding RNA LINC01133 inhibits epithelial–mesenchymal transition and metastasis in colorectal cancer by interacting with SRSF6

Long non-coding RNAs (lncRNAs) play crucial roles in many biological and pathological processes, including tumor metastasis. Here we reported a novel lncRNA, LINC01133 that was downregulated by TGF-β, which could inhibit epithelial-mesenchymal transition (EMT) and metastasis in colorectal cancer (CRC) cells. An alternative splicing factor SRSF6 was identified to directly interact with LINC01133, and SRSF6 promoted EMT and metastasis in CRC cells independent of LINC01133 And we confirmed that the EMT process was regulated by LINC01133 in CRC cells dependent on the presence of SRSF6. The observation for LINC01133 to inhibit metastasis was also verified in vivo. Moreover clinical data showed that the LINC01133 expression was positively correlated with E-cadherin, and negatively correlated with Vimentin, and there was a robust association of low LIINC01133 expression in tumors with poor survival in CRC samples. These data suggest that LINC01133 inhibits the EMT and metastasis by directly binding to SRSF6 as a target mimic, and may serve as a prognostic biomarker and an effective target for anti-metastasis therapies for CRC.

GDF15 promotes EMT and metastasis in colorectal cancer

Metastasis is the major cause of cancer deaths, and the epithelial–mesenchymal transition (EMT) has been considered to be a fundamental event in cancer metastasis. However, the role of growth differentiation factor 15 (GDF15) in colorectal cancer (CRC) metastasis and EMT remains poorly understood. Here, we showed that GDF15 promoted CRC cell metastasis both in vitro and in vivo. In addition, the EMT process was enhanced by GDF15 through binding to TGF-β receptor to activate Smad2 and Smad3 pathways. Clinical data showed GDF15 level in tumor tissues, and the serum was significantly increased, in which high GDF15 level correlated with a reduced overall survival in CRC. Thus, GDF15 may promote colorectal cancer metastasis through activating EMT. Promisingly, GDF15 could be considered as a novel prognostic marker for CRC in the clinic.

Association between dietary antioxidant vitamins intake/blood level and risk of gastric cancer.

We aimed to systematically evaluate the association between dietary intake/blood levels of antioxidant vitamins (vitamin C, vitamin E, β‐carotene, and α‐carotene) and gastric cancer risk. Systematic literature searches were conducted until April 2013 in Pubmed and Embase to identify relevant studies. Either a fixed‐ or a random‐effects model was adopted to estimate overall odds ratios (ORs). Dose–response, meta‐regression, subgroup, and publication bias analyses were applied. Forty articles were finally included in the present study. Higher dietary intake of vitamin C, vitamin E, β‐carotene, and α‐carotene was inversely associated with gastric cancer risk (for vitamin C, pooled OR = 0.58, 95% CI 0.51–0.65; for vitamin E, pooled OR = 0.65, 95% CI 0.57–0.74; for β‐carotene, pooled OR = 0.59, 95% CI 0.49–0.70; for α‐carotene, pooled OR = 0.69, 95% CI 0.52–0.93). Subgroup analyses suggested the effects of these antioxidant vitamins were different in gastric cancer subtypes. As indicated by dose–response analysis, a 100 mg/day increment of vitamin C intake conferred an OR of 0.78 (95% CI 0.67–0.90); a 15 mg/day increment of vitamin E intake conferred an OR of 0.79 (95% CI 0.66–0.94); and a 5 mg/day increment in β‐carotene intake conferred an OR of 0.80 (95% CI 0.60–1.04). No significant association was observed between blood vitamin C, α‐tocopherol, γ‐ tocopherol, β‐carotene and α‐carotene levels and gastric cancer risk. In conclusion, dietary intake of vitamin C, vitamin E, β‐carotene and α‐carotene was inversely associated with gastric cancer risk while no such association was observed for blood levels of these antioxidant vitamins, thus the results should be interpreted cautiously.

Cypermethrin Induces Macrophages Death through Cell Cycle Arrest and Oxidative Stress-Mediated JNK/ERK Signaling Regulated Apoptosis

Cypermethrin is one of the most highly effective synthetic pyrethroid insecticides. The toxicity of cypermethrin to the reproductive and nervous systems has been well studied. However, little is known about the toxic effect of cypermethrin on immune cells such as macrophages. Here, we investigated the cytotoxicity of cypermethrin on macrophages and the underlying molecular mechanisms. We found that cypermethrin reduced cell viability and induced apoptosis in RAW 264.7 cells. Cypermethrin also increased reactive oxygen species (ROS) production and DNA damage in a dose-dependent manner. Moreover, cypermethrin-induced G1 cell cycle arrest was associated with an enhanced expression of p21, wild-type p53, and down-regulation of cyclin D1, cyclin E and CDK4. In addition, cypermethrin treatment activated MAPK signal pathways by inducing c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 ERK1/2 phosphorylation, and increased the cleaved poly ADP-ribose polymerase (PARP). Further, pretreatment with antioxidant N-acetylcysteine (NAC) effectively abrogated cypermethrin-induced cell cytotoxicity, G1 cell cycle arrest, DNA damage, PARP activity, and JNK and ERK1/2 activation. The specific JNK inhibitor (SP600125) and ERK1/2 inhibitor (PD98059) effectively reversed the phosphorylation level of JNK and ERK1/2, and attenuated the apoptosis. Taken together, these data suggested that cypermethrin caused immune cell death via inducing cell cycle arrest and apoptosis regulated by ROS-mediated JNK/ERK pathway.

Association between zinc intake and risk of digestive tract cancers: A systematic review and meta-analysis

BACKGROUND & AIMS Association between zinc intake and digestive tract cancers risk has been reported in several epidemiological studies, while the results were controversial. The aim of our study was to get a systemic review of this issue. METHODS PUBMED and EMBASE were searched up to April 2013, supplemented with manual-screening for relevant articles. Two independent reviewers independently extracted data from eligible studies, risk ratio (RR) or odds ratio (OR) with 95% CIs for the highest versus lowest categories of zinc intake was adopted. Either a fixed- or a random-effects model was adopted to estimate overall odds ratios. Besides, dose-response, subgroup, and publication bias analyses were applied. RESULTS Nineteen studies with approximately 400,000 participants were included in this meta-analysis. The pooled relative risk (RR) of overall digestive tract cancers for the highest versus lowest categories of zinc intake was 0.82 (95% CI: 0.70-0.96; p = 0.013). Comparing the highest with lowest categories, higher zinc intake was significantly associated with reduced colorectal cancer risk (pooled RR = 0.80, 95% CI: 0.70-0.92; p = 0.002), while zinc intake was not statistically associated with gastric cancer risk (pooled RR = 0.91, 95% CI: 0.64-1.29; p = 0.581) or esophageal cancer risk (pooled RR = 0.72, 95% CI: 0.44-1.17; p = 0.187). However, subgroup analyses showed that zinc intake was significantly associated with esophageal cancer risk and gastric cancer risk in Asia, but not in America and Europe. CONCLUSIONS Dietary zinc intake was inversely associated with digestive tract cancers, especially colorectal cancer risk in this study.