AICAR attenuates postoperative abdominal adhesion formation by inhibiting oxidative stress and promoting mesothelial cell repair.

BACKGROUND: Postoperative abdominal adhesion is one of most common complications after abdominal operations. 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) is an adenosine 5'-monophosphate activated protein kinase (AMPK) pathway agonist that inhibits inflammation, reduces cell fibrosis and cellular reactive oxygen species (ROS) injury, promotes autophagy and mitochondrial function. This study aimed to explore the mechanism of AICAR in inhibiting adhesion formation. MATERIALS AND METHODS: Forty rats were randomly divided into five groups. All of the rats except the sham group received cecal abrasion to establish an adhesion model. The rats in the sodium hyaluronate group were treated with 2 mL sodium hyaluronate before closing the peritoneal cavity. The AICAR 1 and 2 groups were treated with 100 mg/kg and 200 mg/kg AICAR, respectively. Seven days after the operation, all of the rats were euthanized, and the adhesion condition was evaluated by Nair's system. Inflammation was assessed by Eosin-hematoxylin (HE) staining and transforming growth factor-ß (TGF-ß1) detection. Oxidative stress effect was determined by ROS, nitric oxide (NO) level, superoxide dismutase (SOD), catalase, glutathione peroxidase (Gpx) and malondialdehyde (MDA) levels in adhesion tissue. Then, Sirius red picric acid staining was used to detect the fiber thickness. Immunohistochemical staining of cytokeratin-19 (CK-19), alpha-smooth muscle actin (α-SMA) and nuclear factor erythroid 2-related factor 2 (Nrf2) was also performed. Finally, HMrSV5 cells were treated with TGF-ß1 and AICAR, the mRNA expression of E-cadherin, α-SMA and vimentin was assessed by q-PCR and cellular immunofluorescent staining. RESULTS: The rats in the AICAR-treated group had fewer adhesion formation incidences and a reduced Nair's score. The inflammation was determined by HE staining and TGF-ß1 concentration. The ROS, SOD, Catalase, Gpx, MDA levels and fiber thickness were decreased by AICAR treatments compared to the control. However, the NO production, Nrf2 levels and peritoneal mesothelial cell integrity were promoted after AICAR treatments. In vitro work, AICAR treatments reduced E-cadherin, α-SMA and vimentin mRNA level compared to that in the TGF-ß1 group. CONCLUSION: AICAR can inhibit postoperative adhesion formation by reducing inflammation, decreasing oxidative stress response and promoting peritoneal mesothelial cell repair.

LncRNA LINC02253 activates KRT18/MAPK/ERK pathway by mediating N6-methyladenosine modification of KRT18 mRNA in gastric cancer.

Long non-coding RNAs (lncRNAs) play a crucial role in gastric cancer (GC) progression. And understanding the role of N6-methyladenosine (m6A) in tumorigenesis is an emerging field in cancer research. Here, we identified a novel oncogene, lncRNA LINC02253, in GC. LINC02253 expression was found to be significantly increased in GC. And LINC02253 expression was closely correlated with tumor size, lymph node metastasis and TNM stage of GC. Besides, GC patients with higher LINC02253 expression had worse 5-year overall survival. Additionally, LINC02253 promoted GC cell growth, migration and invasion both in vitro and in vivo. Mechanistically, we determined that LINC02253 increased KRT18 expression through enhancing the stability of KRT18 mRNA. Furthermore, LINC02253 increased m6A modification of KRT18 mRNA to stabilize KRT18 mRNA by recruiting m6A writer METTL3. And, rescue experiments revealed that KRT18 mediated the effects of LINC02253 on growth, migration and invasion of GC cells through activating MAPK/ERK signaling pathway. In conclusion, we demonstrates that oncogenic lncRNA LINC02253 positively regulates GC growth and metastasis via increasing METTL3-mediated mRNA stability of KRT18, extending the understanding of GC pathogenesis regulated by lncRNAs.

Luteolin exerts an anticancer effect on gastric cancer cells through multiple signaling pathways and regulating miRNAs.

Accumulating studies confirmed that luteolin, a common dietary flavonoid which is widely distributed in plants and has diverse beneficial biological function, including anti-oxidant, anti-inflammation and anticancer properties. However, the detail mechanisms of luteolin on GC are poorly understood. Here, we investigated the anticancer effect of luteolin in GC cells in vitro and in vivo. Luteolin reduced the cell viability in a time and dose-dependent manner. Luteolin significantly inhibited cell cycle progress, colony formation, proliferation, migration, invasion and promoted apoptosis in vitro and in vivo. Luteolin also regulated these biological effects associated regulators. Mechanically, luteolin treatment regulated Notch1, PI3K, AKT, mTOR, ERK, STAT3 and P38 signaling pathways and modulated a series of miRNAs expression. These findings provide novel insight into the molecular function of luteolin which suggest its potential as a therapeutic agent for human GC.

[Efficacy comparison of laparoscopic versus open tension-free hernia repair using biologic mesh for inguinal strangulated hernia].

OBJECTIVE: To compare the efficacy of laparoscopic versus open tension-free mesh repair using biologic mesh for inguinal strangulated hernia. METHODS: Clinical data of 27 patients with inguinal strangulated hernia in the Shanxi Provincial People's Hospital between January 2012 and April 2014 were analyzed retrospectively. All the patients underwent one-stage tension-free repair using biological mesh, including laparoscopic(n=13) and open procedures(n=14). RESULTS: As compared with the open group, the laparoscopic group had shorter operative time [(90.8±11.6) min vs. (130.8±32.5) min, P<0.01], lower rates of hematoma/seroma and wound infection[(7.7% vs. 42.9%) and (0 vs. 28.6%) respectively, both P<0.05], faster recovery of bowel function [(2.5±0.3) d vs. (3.8±1.4) d, P<0.01], and shorter hospital stay [(6.3±1.8) d vs. (9.8±3.2) d, P<0.01]. The mean follow-up was 5.7 months (ranged from 2 to 12 months), and no recurrence or serious complications occurred. CONCLUSION: Laparoscopic tension-free hernia repair using biological mesh for inguinal strangulated hernia has significant advantage versus open operation.

DUSP10 gene polymorphism and risk of colorectal cancer in the Han Chinese population.

Dual-specificity protein phosphatases (DUSP) negatively regulate members of the mitogen-activated protein kinase superfamily, which is associated with cellular proliferation and differentiation. A recent study suggests that DUSP10 is frequently upregulated in colorectal cancer (CRC). Our study aimed to assess whether DUSP10 contributes to the risk of CRC. We analyzed nine tag single nucleotide polymorphisms (tSNPs) of DUSP10 in a case-control study of Han Chinese by the χ²-test and the SHEsis software. We found that two tSNPs (rs908858, P=0.00004; rs11118838, P=0.02510) were significantly associated with CRC using the χ²-test. Using the SHEsis software, six tSNPs (rs12041033, rs17010629, rs12724393, rs12036163, rs11118838, rs12044821) were found in the same linkage disequilibrium block. Within this linkage disequilibrium block, haplotype 'CTCAAC' showed an increased risk of CRC by 42%. By global haplotype analysis, we found that the haplotype 'ACTCAACTA' may increase the risk of CRC by ∼53%; the haplotype 'GCCCACCCA' may decrease the risk by ∼46%. Our results, combined with previous studies, suggest that certain mutations in DUSP10 correlate with the incidence of CRC. Thus, the function of the DUSP10 gene product may contribute toward CRC in the Han Chinese population.