PID1 based connection of insulin resistance to hepatocellular carcinogenesis

OBJECTIVE To investigate the effect of phosphotyrosine interaction domain containing1(PID1,NYGGF4) onpromotion of IR and HCC,and explore its underlying mechanisms.METHODS Lentivirus were used to mediate the knockdown of PID1 in HFD induced IR mouse model as well as ob/ob mice.Intraperitoneal glucose and insulin tolerance were performed 4 weeks after lentivirus injection.Hydrodynamics-based transfection was applied to induce the liver specific overexpression of PID1.Flow cytometry was exerted to detect the proportion and function of immune cells.qRT-PCR and Western blot were used to detect the expression of downstream pathways of PID1.Liquid chromatographymass spectrometry(LC-MS) and co-immunoprecipitation(Co-IP) were conducted to identify proteins interacting with PID1.Chromatin immunoprecipitation(ChIP) was operated to measure the modification of H3K4me3 of PID1 promoter.RESULTS PID1 restriction improved insulin resistance,hyperglycemia and fatty liver.Conversely,hepatic knockdown of PID1 attenuated liver xenografted tumor growth.Moreover,PID1 liver-specific protooncogenes via hydrodynamics-based transfection established a primary hepatocellular carcinoma mouse model,induced an immunosuppressive environment,with the reduction of CD3+,CD4+,CD8+T cells,retarded maturation of dendritic cells(DCs),pronounced differentiation of regulatory T cells(Tregs),and recruitment of MDSC.In addition,PID1 overexpression activated prolifer.ation related genes,promoted anti-inflammatory genes,suppressed pro-inflammatory genes,induced glycolysis and lipid metabolism genes to facilitate tumorigenesis in liver.Importantly,PID1 exerted its tumor-promoting function through binding to epidermal growth factor receptor(EGFR) and activation of downstream KRAS/ERK pathway.As such,PID1 exist trimethylation of histone H3 at lysine 4(H3K4me3)modification and IR up-regulated the expression of PID1 by activation the H3K4me3 modification.CONCLUSION PID1 is a new gene that exerts both liver cancer-promoting and insulin resistance inducing function.IR accelerates liver cancer development and progression partially dependent on the activation of PID1.

Increased expression of matrix metalloproteinase-9 associated with gastric ulcer recurrence

AIM: To compare matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in gastric ulcer (GU) and chronic superficial gastritis (CSG). METHODS: This study enrolled 63 patients with GU and 25 patients with CSG. During upper gastroduodenal endoscopy, we took samples of gastric mucosa from the antrum and ulcer site from patients with GU, and samples of antral mucosa from patients with CSG. Mucosal biopsy tissues were cultured for 24 h, and the culture supernatant was measured for levels of MMP-9 and TIMP-1. After receiving eradication therapy for Helicobacter pylori (H. pylori ) and 8 wk proton-pump inhibitor therapy for GU, follow-up endoscopy examination was performed after 6 mo and whenever severe symptoms occurred. RESULTS: Levels of MMP-9 and TIMP-1 at the ulcer site or in the antrum were significantly higher in GU than CSG patients. MMP-9 levels at the ulcer site were significantly higher than in the antrum in GU patients, and had a significantly positive correlation with TIMP-1. MMP-9 levels were significantly higher in H. pylori -positive than H. pylori -negative GU and CSG patients. Levels of MMP-9 or TIMP-1 at the ulcer site were associated with the histological severity of activity and inflammation. About 57 GU patients were followed up, and seven had GU recurrence. H. pyloriinfection and MMP-9 levels were risk factors for the recurrence of GU adjusted for age and sex by multiple logistic regression analysis. CONCLUSION: MMP-9 may perform an important function in gastric ulcer formation and recurrence.

Combination of concurrent endoscopic submucosal dissection and modified peroral endoscopic myotomy for an achalasia patient with synchronous early esophageal neoplasms

Achalasia is generally accepted as a condition associated with an increased risk for developing esophageal squamous cell carcinoma. In our paper, we introduced an achalasia patient combined with synchronous early esophageal neoplasms. We performed a combination of concurrent endoscopic submucosal dissection(ESD) and peroral endoscopic myotomy(POEM). No complications other than postoperative pain that needed morphine treatment for two days had occurred. Dysphagia was significantly improved. Neither reflux nor cough occurred. The short-term efficacy and safety of our case is favorable and suggests that concurrent ESD and POEM could be a treatment option to such patients.

Microfabrication technology for non-coplanar resonant beams and crab-leg supporting beams of dual-axis bulk micromachined resonant accelerometers

This paper presents the design principles and fabrication techniques for simultaneously forming non-coplanar resonant beams and crab-leg supporting beams of dual-axis bulk micromachined resonant accelerometers by masked-maskless combined anisotropic etching.Four resonant beams are located at the surface of a silicon substrate,whereas the gravity centre of a proof mass lies within the neutral plane of four crab-leg supporting beams on the same substrate.Compared with early reported mechanical structures,the simple structure not only eliminates the bending moments caused by in-plane acceleration,and thereby avoiding the rotation of the proof mass,but also providing sufficiently small rigidity to X and Y axes accelerations,potentially leading to a large sensitivity for measuring the in-plane acceleration.