Guoqiang Lv

The TNF-Alpha-238 Polymorphism and Cancer Risk: A Meta-Analysis

Background and Objectives Tumor necrosis factor-α (TNF-α) plays a very important role in the development and progress of cancer. Some TNF-α polymorphisms have been confirmed to increase cancer risks; however, the association between TNF-α-238 polymorphism and cancers remains controversial and ambiguous. The aim of this study is to explore a more precise estimation of its relationship with cancer using meta-analysis. Methods Electronic searches of several databases were conducted for all publications on the association between this variant and cancer through March 2011. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association in the random-effect model. Results Thirty four studies with 34,679 cancer patients and 41,186 healthy controls were included. This meta-analysis showed no significant association between TNF-α-238 polymorphism and cancers (AA+GA vs GG: OR = 1.09, 95%CI = 0.88–1.34). In Caucasian and Asian subgroups, OR values (95% CI) were 1.14 (0.91–1.43) and 0.97 (0.58–1.61), respectively. In the subgroups of cancer type, no significant association was detected. The sensitivity analysis further strengthened the validity of these negative associations. No publication bias was observed in this study. Conclusions No significant association was found between the TNF-α-238 polymorphism and the risk for cancer.

Lower irisin level in patients with type 2 diabetes mellitus: A case‐control study and meta‐analysis

Irisin is a newly identified myokine in mice and humans. Many studies have reported irisin concentrations in patients with type 2 diabetes mellitus (T2DM). The large variations in irisin concentrations in different studies may be attributable to differences in sample size or populations. The aim of the present study was to establish an accurate confidence interval of irisin levels in T2DM patients using a case‐control study and large‐scale meta‐analysis.

Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

Half of the worlds population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK-HO-1 signaling.

AMP-activated protein kinase activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis

Helicobacter pylori (H pylori), infecting half of the worlds population, causes gastritis, duodenal and gastric ulcer, and gastric cancers. AMP-activated protein kinase (AMPK) is a highly conserved regulator of cellular energy and metabolism. Recent studies indicated an important role for AMPK in promoting cell survival. In this study, we discovered that H Pylori induced AMPK activation in transformed (GEC-1 line) and primary human gastric epithelial cells (GECs). Inhibition of H Pylori-stimulated AMPK kinase activity by AMPK inhibitor compound C exacerbated apoptosis in transformed and primary GECs. Meanwhile, downregulation of AMPK expression by targeted shRNAs promoted apoptosis in H pylori-infected GECs. In contrast, A-769662 and resveratrol, two known AMPK activators, or AMPKα1 over-expression, enhanced H Pylori-induced AMPK activation, and inhibited GEC apoptosis. Our data suggested that transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) could be the upstream kinase for AMPK activation by H pylori. Partial depletion of TAK1 by shRNAs not only inhibited AMPK activation, but also suppressed survival of H pylori-infected GECs. Taken together, these results suggest that TAK1-dependent AMPK activation protects GECs from H pylori-Induced apoptosis.

Lack of Association of SULT1A1 R213H Polymorphism with Colorectal Cancer: A Meta-Analysis

Background A number of case-control studies were conducted to investigate the association of SULT1A1 R213H polymorphisms with colorectal cancer (CRC) in humans. But the results were not always consistent. We performed a meta-analysis to examine the association between the SULT1A1 R213H polymorphism and CRC. Methods and Findings Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Excerpta Medica Database, and Chinese Biomedical Literature Database, with the last report up to September 2010. A total of 12 studies including 3,549 cases and 5,610 controls based on the search criteria were involved in this meta-analysis. Overall, no significant association of this polymorphism with CRC was found (H versus R: OR = 1.04, 95%CI = 0.94–1.16, P = 0.46; HR+HH versus RR: OR = 1.01, 95%CI = 0.92–1.11, P = 0.81; HH versus RR+HR: OR = 1.01, 95%CI = 0.74–1.38, P = 0.95; HH versus RR: OR = 1.00, 95%CI = 0.77–1.31, P = 0.98; HR versus RR: OR = 1.01, 95%CI = 0.92–1.11, P = 0.86). In subgroup analysis, we also did not find any significant association in Cauasians (H versus R: OR = 1.02, 95%CI = 0.92–1.15, P = 0.68; HR+HH versus RR: OR = 0.99, 95%CI = 0.91–1.09, P = 0.90; HH versus RR+HR: OR = 1.01, 95%CI = 0.73–1.39, P = 0.97; HH versus RR: OR = 0.99, 95%CI = 0.75–1.31, P = 0.94; HR versus RR: OR = 0.99, 95%CI = 0.90–1.09, P = 0.85). The results were not materially altered after the studies which did not fulfill Hardy-Weinberg equilibrium were excluded (H versus R: OR = 1.06, 95%CI = 0.95–1.19, P = 0.31; HR+HH versus RR: OR = 1.03, 95%CI = 0.93–1.13, P = 0.56; HH versus RR+HR: OR = 1.10, 95%CI = 0.78–1.56, P = 0.57; HH versus RR: OR = 1.09, 95%CI = 0.83–1.44, P = 0.53; HR versus RR: OR = 1.02, 95%CI = 0.92–1.13, P = 0.75). Conclusion This meta-analysis demonstrates that there is no association between the SULT1A1 R213H polymorphism and CRC.

Dandelion root extract suppressed gastric cancer cells proliferation and migration through targeting lncRNA-CCAT1

Gastric cancer (GC) is one of the most common tumors worldwide. Standard treatment after early detection involves surgical excision (recurrence is possible), and metastatic gastric cancer is refractory to immuno-, radio-, and most harmful chemotherapies. Various natural compounds have shown efficacy in killing different cancers, albeit not always specifically. In this study, we show that dandelion root extract (DRE) specifically and effectively suppresses proliferation and migration in human gastric cells without inducing toxicity in noncancerous cells. Long noncoding RNAs (lncRNAs) are known to promote tumorigenesis in many cancer types. Here, we showed that the lncRNA colon cancer-associated transcript-1 (CCAT1) was down-regulated in dandelion-treated GC cells. Furthermore, downregulation of CCAT1 inhibited proliferation and migration of gastric cells. We also found that DRE exerted its function in GC cells partially through targeting CCAT1. This data will provide a basis on which further research in cancer treatment through DRE can be executed.

Comments on adolescent intakes of vitamin D and calcium and incidence of proliferative benign breast disease

We read with great interest the article by Su et al. [1] published in May 2012. This retrospective study reported some interesting observations and discussions on vitamin D intake and incidence of proliferative benign breast disease from a large population. However, we feel that it might be necessary to discuss some concerns on the methods and conclusions out of interpretation in this study. Recently, some interesting articles about the associations between the vitamin D and breast diseases have been published in this journal [2–8]. However, vitamin D intake does not represent the extent of vitamin D deficiency, which is mostly defined by the serum vitamin D level (25(OH) D.\20–30 ng/mL) [2, 3, 6, 9]. Because vitamin D deficiency is related to dietary, sun exposure, and/or metabolic factors: 20 % vitamin D is obtained from food (fish, eggs, animal livers, dairy products), while 80 % from skin synthesis as a product of skin 7-dehydrocholesterol transformations, induced by ultraviolet radiation [10]. In their study, it might be unreliable to use vitamin D intake to determine the associations between vitamin D status and incidence of proliferative benign breast disease. We believe that the sun exposure should be taken into consideration as covariate, and also the true serum vitamin D levels should be included for sample grouping as previous studies conducted [2, 3, 11, 12]. If these analyses could not be conducted, these confounding factors should be welldiscussed in this article. Another point is that whether lifestyles of the subjects were changed after high school. If the lifestyles were changed significantly, researchers may consider its influence when drawing the final conclusions. We believe that information on these issues mentioned above would, with no doubt, help readers understand the findings of this article more clearly.