[Retracted] P21 activated kinase 2 promotes pancreatic cancer growth and metastasis.

[This retracts the article DOI: 10.3892/ol.2019.10040.].

S1P/S1PR2 promote pancreatic stellate cell activation and pancreatic fibrosis in chronic pancreatitis by regulating autophagy and the NLRP3 inflammasome.

Sphingosine-1-phosphate (S1P) is a bioactive lipid molecule that governs various functions by embedding its receptor, S1PR, in different cells. Chronic pancreatitis (CP) is characterized by pancreatic fibrosis via activation of pancreatic stellate cells (PSCs). However, the effect of S1P on CP and PSC activation is still unknown. Here, we conducted a series of experiments to explore the effect of S1P on a CP rat model and primary cultured PSCs. In vivo, CP was induced by intravenous injection of dibutyltin dichloride. S1P was administered at a dosage of 200 µg/kg body weight per day by intraperitoneal injection. After 4 weeks, serum, plasma and pancreas samples were collected for molecular analysis and histological detection. In vitro, PSCs were isolated and cultured for treatment with different doses of S1P. 3MA and MCC950 were used to determine the effect of S1P on PSC activation by regulating autophagy and the NLRP3 inflammasome. JTE013 and Si-S1PR2 were applied to verify that the functions of S1P were realized by combining with S1PR2. Cells were collected for RT‒PCR, western blotting and immunofluorescence. The results showed that S1P was increased in the plasma and pancreatic tissue of CP rats. When S1P was administered to CP rats, the function and histomorphology of the pancreas were severely impaired. In addition, S1P promoted PSC activation, heightened autophagy and enhanced the NLRP3 inflammasome in vivo and in vitro. Moreover, S1PR2 mediated the effect of S1P on PSC activation by regulating autophagy and the NLRP3 inflammasome sequentially. In conclusion, S1P binding to S1PR2 promoted PSC activation and pancreatic fibrosis in CP by regulating autophagy and the NLRP3 inflammasome. These findings provide a theoretical basis for targeting S1P/S1PR2 to treat pancreatic fibrosis and further suggest that considering the role of autophagy and the NLRP3 inflammasome may help with the treatment pancreatic fibrosis.

[Characteristics of Bacterial Community Structure in Wuliangsu Lake During an Irrigation Interval in Hetao Plain].

In order to study the bacterial community composition and corresponding function in Wuliangsu Lake at the end of the Hetao Plain during the irrigation gap period, lake samples were collected in September 2020, and the pH, TN, TP, DIP, DTP, NH4+-N, Chla, EC, SAL, and other indicators were analyzed. The 16S rRNA high-throughput sequencing method was used to explore the attached bacteria and bacterioplankton in 15 samples of the surface water in Wuliangsu Lake. The experimental results showed that:① the alpha diversity Chao and Shannon indices of attached bacteria were greater than that of bacterioplankton, but the median of Shannoneven index was the same. ② In each sampling point, the bacterioplankton of Proteobacteria and Actinobacteria in the top five dominant bacteria phyla were higher than that of attached bacteria, and the abundance of attached bacteria and bacterioplankton of Bacteroidota were staggered. On the contrary, the contents of attached bacteria of Verrucomicrobiota and Cyanobacteria were all higher than that of bacterioplankton. ③ Redundant analysis showed that pH had the most significant effect on dominant attached bacteria, and the effect of conductivity and salinity in dominant bacterioplankton was the most significant. ④ PICRUSt2 function prediction analysis showed that attached bacteria and planktonic bacteria had the strongest metabolic functions, showing abundant metabolic functions. There were 29 nitrogen-related effective KOs and 88 phosphorus-related effective KOs, with the greatest nitrogen-fixing function and strong inorganic phosphorus-dissolving function, and bacterioplankton played a greater role in the two functions.

Erratum: P21 activated kinase 2 promotes pancreatic cancer growth and metastasis.

[This corrects the article DOI: 10.3892/ol.2019.10040.].

P21 activated kinase 2 promotes pancreatic cancer growth and metastasis.

Pancreatic cancer has an overall 5-year survival rate of only 9%, due to its rapid metastasis and poor prognosis. To combat this disease, novel therapeutic targets and biomarkers are required. In this study, immunohistochemistry was used to detect the expression of P21 activated kinase 2 (PAK2) protein in the tissues of cancer and the paired adjacent normal tissues. The association between PAK2 and the clinicopathologic features of patients with pancreatic cancer was subsequently analyzed. The results indicated that PAK2 was overexpressed in the cancer tissues, which indicated high pTNM stage, poor tumor grade, lymph node metastasis and vascular invasion. In addition, the results demonstrated evidence of a close association between PAK2 expression and poor prognosis of patients with pancreatic cancer. The results also suggested that PAK2 may promote pancreatic cancer cell proliferation and migration in vitro through clone formation, MTT, wound healing and Transwell assays. The present study further identified that PAK2 could stimulate pancreatic cancer growth and metastasis in mice. Decreased expression of proliferation marker protein Ki-67 and proliferating cell nuclear antigen in response to PAK2 knockdown further verified the role of PAK2 in promoting cell proliferation by western blot analysis. In addition, the expression levels of matrix metallopeptidase (MMP) 2 and MMP9 were decreased in PANC1 and BxPC3 cell lines transfected with PAK2-short hairpin RNA as indicated in western blot analysis, suggesting a function of PAK2 in promoting cell invasion. Collectively, these findings revealed a critical role for PAK2 in the development of pancreatic cancer and may have important implications for the management of this disease.

JinQi Jiangtang Tablet Regulates Gut Microbiota and Improve Insulin Sensitivity in Type 2 Diabetes Mice.

BACKGROUND: Gut microbiota modulates the barrier function and host inflammatory state in metabolic disease. JinQi Jiangtang (JQJT) tablets are a traditional Chinese medicine for the treatment of diabetes. However, the low bioavailability of its chemical compositions makes it hard to explain the pharmacological mechanisms. METHOD: Diabetic mice were orally treated with JQJT tablets for 5 weeks. Fasting blood glucose and the level of HbA1c were measured, and ITT were conducted to determine the insulin improvement effect of JQJT tablets. The regulation effect on gut microbiota was assessed by 16S rRNA gene sequencing on an Illumina HiSeq platform. The concentration of short-chain fatty acids was measured by HS-GC/MS. D-LA leakage experiment and PAS staining were used to check the function of the gut barrier. The levels of the inflammatory cytokines were determined by using an ELISA kit. RESULTS: This study showed that JQJT tablets downregulated fasting blood glucose and HbA1c and regulated gut microbiota. JQJT tablet-treated groups exhibited a more sensitive reaction after a small-dose injection of short-acting insulin. T2DM mice treated with JQJT tablets showed a higher abundance of Akkermansia spp. and lower abundance of Desulfovibrio. JQJT tablets increased the concentration of acetic acid, propionic acid, and butyric acid; in particular, butyric acid was significantly increased with respect to the MOD group. Gut mucosal barrier function experiment showed that the level of D-LA was obviously decreased in JQJT tablet-treated groups compared with the model group and the number of goblet cells was significantly increased by JQJT tablet treatment. JQJT tablets could also reduce the levels of TNF-α, IL-6, and MCP-1, which were related to insulin resistance. CONCLUSION: We demonstrated that JQJT tablets could improve T2DM insulin resistance, regulating the gut microbiota and promoting the production of SCFAs. The mechanism was related to increasing the gut barrier function and reducing the host inflammatory reaction.

AFP-negative mixed hepatoid adenocarcinoma of the colon: a case report with review of literature.

AIM: To investigate the clinicopathologic profile of hepatoid adenocarcinoma (HAC) of the colon and to improve the diagnostic and treatment level. MATERIALS AND METHODS: The clinical observations and histopathologic and immunohistochemical features of HAC were analyzed. RESULTS: HAC is usually composed of well-differentiated common adenocarcinoma and hepatoid differentiation. The tumor cells in hepatoid differentiation area are arranged in trabecular or solid shape, with large polygonal tumor cells, and abundant cytoplasm. Immunohistochemical markers showed the HAC cells were positive for Glypican-3, HepPar1, CK19, and carcinoembryonic antigen (CEA), while alpha-fetoprotein (AFP) was negative. CONCLUSION: HAC is a rare malignant tumor of the colon. Its diagnosis depends on histopathology and immunohistochemical staining. Surgical resection should be the treatment of choice if possible.