Apelin-13/APJ system delays intervertebral disc degeneration by activating the PI3K/AKT signaling pathway.

OBJECTIVE: To study the effect of Apelin-13/APJ system on intervertebral disc degeneration and its mechanism. PATIENTS AND METHODS: This study detected the expression of APJ in human intervertebral disc tissue with varying degrees of degeneration. IL-1ß is used to stimulate the degeneration of nucleus pulposus cells. We used recombinant human Apelin-13 and Ala13 to activate and inhibit the APJ receptor, respectively. The inhibitor LY294002 was used to inhibit the PI3K/AKT signaling pathway. We studied the effects of Apelin-13/APJ system on nucleus pulposus cells and its mechanism by Western blot, RT-PCR, and so on. RESULTS: APJ is lowly expressed in the nucleus pulposus of patients with a high degree of degeneration. IL-1ß stimulates the nucleus pulposus cells and reduces the expression of APJ in nucleus pulposus cells. Recombinant human Apelin-13 reduces the degradation of nucleus pulposus extracellular matrix, promotes proliferation, and reduces the levels of apoptosis and inflammation. In addition, the Apelin-13/APJ system increases the expression of PI3K and AKT and activates the PI3K/AKT signaling pathway. CONCLUSIONS: Apelin-13/APJ system activates PI3K/AKT signaling pathway activity, reduces the degradation of nucleus pulposus extracellular matrix, promotes proliferation, and reduces the level of apoptosis and inflammation, thus delaying the degeneration of the intervertebral disc.

Helicobacter pylori infection and normal colorectal mucosa-adenomatous polyp-adenocarcinoma sequence: a meta-analysis of 27 case-control studies.

AIM: The study aimed to determine whether Helicobacter pylori infection is associated with colorectal adenocarcinoma and to quantify the extent of the risk. METHOD: A literature search was performed to identify studies published between 1995 and 2012 for relevant risk estimates. Fixed and random effect meta-analytical techniques were conducted for colorectal adenocarcinoma and adenomatous polyp. RESULTS: Twenty-seven case-controlled studies involving 3450 adenocarcinoma patients, 1304 adenomatous polyp patients and more than 4000 controls were included. Helicobacter pylori was associated with an increased risk of colorectal adenocarcinoma and adenomatous polyp [odds ratio (OR) 1.24, 95% CI 1.12-1.37, P = 0.66; OR 1.87, 95% CI 1.53-2.28, P = 0.81]. There was a significant association between the CagA-positive strain and adenocarcinoma risk (OR 1.22, 95% CI 1.08-1.37, P = 0.05). In addition, there was an increased risk of tubular adenoma and villous adenoma formation (OR 3.06, 95% CI 1.98-4.73, P = 0.14; OR 2.05, 95% CI 0.84-4.97, P = 0.86). CONCLUSION: The meta-analysis suggests a promoting effect of Helicobacter pylori on the risk of adenocarcinoma. It also suggests that Helicobacter infection might have its influence at the start of the adenomatous polyp disease sequence.

Nonsteroidal anti-inflammatory drugs and esophageal inflammation - Barrett's esophagus - adenocarcinoma sequence: a meta-analysis.

The incidence of esophageal adenocarcinoma has markedly increased in the last few decades and Barrett's esophagus is regarded as the precursor lesion of this cancer. The aim of the study was to quantify the adenocarcinoma risk associated with nonsteroidal anti-inflammatory drug use and to determine at which stage chemoprevention with this drug is the most effective in esophageal inflammation - Barrett's esophagus - adenocarcinoma sequence. A literature search was performed to identify studies published between 1998 and 2009 for relevant risk estimates. Fixed and random effect meta-analytical techniques were conducted for aspirin, nonaspirin nonsteroidal anti-inflammatory drugs, and all nonsteroidal anti-inflammatory drugs. Four cohort and 10 case-control studies were included. Use of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs in normal population was associated with a reduced risk of adenocarcinoma (odds ratio [OR]: 0.73, 95% confidence interval [CI]: 0.65-0.83; OR: 0.84, 95% CI: 0.72-0.98, respectively). The use of all nonsteroidal anti-inflammatory drugs was associated with a reduced risk of adenocarcinoma (relative risk [RR]: 0.64, 95% CI: 0.42-0.96) in Barrett's esophagus patients. However, no obvious dose-effect relationships were found. In addition, we discovered a reverse association between drugs use and adenocarcinoma risk in people without a history of upper gastrointestinal tract disorders (OR: 0.57, 95% CI: 0.43-0.77, P= 0.12). Our meta-analyses suggest a protective effect of nonsteroidal anti-inflammatory drugs on the risk of adenocarcinoma. Our results also suggest that the drugs might act after the formation of Barrett's epithelium in the esophageal inflammation - Barrett's esophagus - adenocarcinoma sequence.