ENO1 contributes to the gemcitabine resistance of pancreatic cancer through the YAP1 signaling pathway.

Pancreatic cancer (PC), a leading cause of cancer-related deaths, has a 5-year survival rate of approximately 10%. α-Enolase (ENO1) is a junction channel protein involved in tumor cell apoptosis and chemoresistance. However, the role of ENO1 in PC remains unclear. The expression and prognosis of ENO1 levels were determined in PC using public databases based on The Cancer Genome Atlas (TCGA) data sets. Cell viability, half maximal inhibitory concentration (IC50), autophagy, apoptosis, and autophagy markers were examined using cell counting kit-8 (CCK-8), transmission electron microscope, flow cytometry assays, and immunoblot, respectively. Using the Gene Expression Omnibus (GEO) and TCGA data sets, we found that ENO1 was significantly enriched in PC tumor tissues, and high expression levels of ENO1 were associated with an unfavorable prognosis. Whereas ENO1 silencing suppressed proliferation, autophagy, and induced cell apoptosis in PC cells, and inhibited tumor growth in vivo. Mechanistically, knockdown of ENO1 enhanced cellular cytotoxicity of gemcitabine (GEM), as well as reducing the expression of yes-associated protein 1 (YAP1), a major downstream effector of the Hippo pathway in vitro. YAP1 promoted autophagy and protected PC cells from GEM-induced apoptotic cell death. Furthermore, YAP1 overexpression attenuated the inhibition effects of ENO1 silencing. Our results suggest that ENO1 overexpression promotes cell growth and tumor progression by increasing the expression of YAP1 in PC. Further studies are required to understand the detailed mechanisms between ENO1 and YAP1 in PC.

Clinical application of pancreatic-duct-jejunum end-to-side continuous suture anastomosis in total laparoscopic pancreaticoduodenectomy.

BACKGROUND: To present a new pancreaticojejunostomy technique for laparoscopic pancreaticoduodenectomy (LPD) and to evaluate its safety and reliability. METHODS: The data of 120 patients who underwent LPD at a single centre from October 2017 to October 2019 were retrospectively analysed. Of these patients, 71 received continuous suture pancreaticojejunostomy, and 49 received "8-character" suture pancreaticojejunostomy for LPD. We compared and analysed the operation time, anastomosis time, and incidence of postoperative complications between the patients in the two groups. RESULTS: All operations were successfully performed, with no transfer to open surgery. The operation time and anastomosis time in the continuous suture group were lower than those in the "8-character" suture group (305.8 ± 60.7 min vs. 354.3 ± 69.1 min; 28.6 ± 6.3 min vs. 39.4 ± 11.9 min P < 0.001), and the postoperative hospital stay was also shorter (12.9 ± 3.8 days vs. 15.4 ± 5.8 days P < 0.05) in the continuous suture group. There was no significant difference in the pancreatic duct diameter or intraoperative blood loss between the two groups. There was also no significant difference in the incidence of a pancreatic fistula between the continuous suture group and the "8-character" suture group. The data of patients in the continuous suture group with pancreatic duct diameters < 3 mm and ≥ 3 mm were statistically analysed. There was no significant difference in the operation time, pancreaticojejunostomy time, postoperative hospital stay, or incidence of pancreatic fistula in the different pancreatic duct diameter groups. CONCLUSIONS: Continuous suture of pancreaticojejunostomy in LPD is simple, safe, reliable, and rapid. This technique not only saves the anastomosis time but also suitable for pancreatic ducts < 3 mm.

Rg1 exerts protective effect in CPZ-induced demyelination mouse model via inhibiting CXCL10-mediated glial response.

Myelin damage and abnormal remyelination processes lead to central nervous system dysfunction. Glial activation-induced microenvironment changes are characteristic features of the diseases with myelin abnormalities. We previously showed that ginsenoside Rg1, a main component of ginseng, ameliorated MPTP-mediated myelin damage in mice, but the underlying mechanisms are unclear. In this study we investigated the effects of Rg1 and mechanisms in cuprizone (CPZ)-induced demyelination mouse model. Mice were treated with CPZ solution (300 mg· kg-1· d-1, ig) for 5 weeks; from week 2, the mice received Rg1 (5, 10, and 20 mg· kg-1· d-1, ig) for 4 weeks. We showed that Rg1 administration dose-dependently alleviated bradykinesia and improved CPZ-disrupted motor coordination ability in CPZ-treated mice. Furthermore, Rg1 administration significantly decreased demyelination and axonal injury in pathological assays. We further revealed that the neuroprotective effects of Rg1 were associated with inhibiting CXCL10-mediated modulation of glial response, which was mediated by NF-κB nuclear translocation and CXCL10 promoter activation. In microglial cell line BV-2, we demonstrated that the effects of Rg1 on pro-inflammatory and migratory phenotypes of microglia were related to CXCL10, while Rg1-induced phagocytosis of microglia was not directly related to CXCL10. In CPZ-induced demyelination mouse model, injection of AAV-CXCL10 shRNA into mouse lateral ventricles 3 weeks prior CPZ treatment occluded the beneficial effects of Rg1 administration in behavioral and pathological assays. In conclusion, CXCL10 mediates the protective role of Rg1 in CPZ-induced demyelination mouse model. This study provides new insight into potential disease-modifying therapies for myelin abnormalities.

Red mud modified sludge biochar for the activation of peroxymonosulfate: Singlet oxygen dominated mechanism and toxicity prediction.

In this paper, red mud-sewage sludge derived biochar (RSDBC) was synthesized and employed as the heterogenous activator of peroxymonosulfate (PMS) for sulfamethoxazole (SMX) degradation. With the incorporation of red mud, 82.5% degradation of SMX was achieved by RSDBC/PMS system in a process dominated by 1O2, which was attributed to the participation of oxygen vacancy, ketone groups and graphitic carbon. On the other hand, in the absence of red mud, OH and SO4•- were dominantly accounted for SMX degradation in sewage sludge derived biochar (SDBC)/PMS system. In this case heterogeneous Fe species, ketone groups and graphitic carbon were responsible for PMS activation. Due to the different Reactive Oxygen Species (ROS), effects of reaction conditions including initial pH, common anions and natural organic matter (NOM) were not in full accord. Besides, Fe leaching from RSDBC (0.67 ppm) was much lower than that of SDBC (3.07 ppm), leading to a better reuse ability for RSDBC. Less degradation intermediates were disclosed in RSDBC/PMS system, along with lower residual toxicity. In addition, eco-toxicity of all the intermediates was predicted by ECOSAR program for the further understanding of the detoxification of SMX. Advantages of RSDBC/PMS system as disclosed in this paper further suggest its potential full-scale application of environmental remediation.

Clinical application of a modified pancreatojejunostomy technique for laparoscopic pancreaticoduodenectomy.

BACKGROUND: The aim of this study was to present a modified pancreatojejunostomy technique for laparoscopic pancreaticoduodenectomy (LPD) and to evaluate its safety and reliability. METHODS: Clinical data from 67 patients who underwent LPD at a single center, from September 2016 to December 2017 were retrospectively collected and analysed. Of these patients, 31 cases were subjected to modified pancreatojejunostomy (modified group), and 36 cases received duct-to-mucosa pancreatojejunostomy (control group) for LPD. We compared and analysed the operative outcomes and postoperative complications between the patients in the two groups. RESULTS: All LPDs were successfully completed. The mean operation time for pancreatojejunostomy in the modified group was obviously lower than that of the control group (30.9 ± 6.6 min vs 45.3 ± 6.1 min, P < 0.01), and the total operative time was also shorter (321.8 ± 63.6 min vs 362.2 ± 59.6 min, P < 0.05) in the modified group. The overall incidence of postoperative complications was similar (29.0% vs 30.6% P = 0.724). Clinically relevant grade B/C POPF occurred in 2 patients (6.5%) in the modified group and 3 patients (8.3%) in the control group (P = 0.947); All cases were cured using conservative treatment. CONCLUSIONS: Our modified pancreatojejunostomy technique is safe, effective and easy to manipulate and learn following LPD.