Expression of VNN1 in Ulcerative Colitis / 胃肠病学

Background: Molecular markers associated with disease progression and prognosis of ulcerative colitis (UC) are still lacking in clinic. Aims: To investigate the expression and clinical significance of vanin 1 (VNN1) in intestinal mucosal tissue, serum and stool in patients with UC. Methods: A total of 100 UC patients and 100 healthy volunteers from Dec. 2018 to Jan. 2020 at the People's Hospital of Xinjiang Uygur Autonomous Region were recruited, and colonoscopy biopsy tissue samples, blood samples and stool samples were collected. PCR, Western blotting and immunohistochemistry were used to detect mRNA and protein expressions of VNN1 in intestinal mucosal tissue, respectively. The expression of VNN1 in serum and stool was determined by ELISA. Results: The mRNA and protein expressions of VNN1 in intestinal mucosal tissue in patients with UC were significantly higher than those in healthy controls (P0.05). Conclusions: The expressions of VNN1 in intestinal mucosal tissue and blood in UC patients are high, and can be used as a molecular marker of UC.

VNN1, a potential biomarker for pancreatic cancer-associated new-onset diabetes, aggravates paraneoplastic islet dysfunction by increasing oxidative stress.

In our previous clinical microarray analysis, we were the first to report on Vanin-1 (VNN1) as a novel clinically derived biomarker of pancreatic cancer-associated new-onset diabetes (PCAND). The functional mechanisms of VNN1 in the pathogenesis of PCAND, however, are not completely understood. In the present study, we further extend our previous clinical study to include laboratory research. The functions and mechanisms of neoplastic overexpressed VNN1 in PCAND have been explored using a co-culture model. Furthermore, the serum concentrations and discrimination power of downstream molecules of VNN1 were tested in a PCAND cohort. Pancreatic ductal adenocarcinoma (PDA) overexpressed VNN1 further aggravates paraneoplastic islet dysfunction; decreases in GSH/PPAR-γ concentrations and increases in ROS/cysteamine might be primary cause of this effect. Clinical serum analyses revealed that the expression profiles of these molecules were aberrant in the PCAND group. Our results further demonstrated that PCAND is a type of paraneoplastic diabetes. As the only clinically derived biomarker for PCAND screening available today, the biological role of VNN1 in triggering oxidative stress within the pancreatic microenvironment is important. The molecules downstream of VNN1 are also potential biomarkers for PCAND screening.

Anthocyanins from Chinese bayberry extract activate transcription factor Nrf2 in ß cells and negatively regulate oxidative stress-induced autophagy.

Islet replacement is a promising cure for insulin-dependent diabetes but is limited by a massive early cell death following transplantation. Overburden oxidative stress is one of the major factors causing cell damage. We have shown previously that anthocyanins in Chinese bayberry extract protected ß cells (INS-1) from hydrogen peroxide (H2O2)-induced apoptosis and decreased grafts' apoptosis after transplantation partially through heme oxygenase-1 (HO-1) up-regulation. In the present study, we observed that H2O2 stimulation induced autophagy in ß cells. Inhibition of autophagy increased cell viability and decreased cell death. Anthocyanin pretreatment attenuated oxidative stress-mediated autophagic cell death. Anthocyanins activated antioxidant transcription factor Nrf2 in INS-1 cells, and Nrf2/HO-1 negatively regulated autophagy process. Furthermore, we here demonstrate that autophagy also took place in ß cell grafts during the early post-transplantation phase. ß Cells pretreated with anthocyanins displayed decreased extent of autophagy after transplantation. Taken together, these findings further supported the conclusion that anthocyanins could serve as a protective agent of ß cells and suggested that autophagy might play a role in ß cells during transplantation.