Expression and Prognostic Value of PIK3CA, VEGF, IL-8, IL-10, and RIP2 in Diffuse Large B-Cell Lymphoma.

Background: To explore clinical features and prognostic value of vascular endothelial growth factor (VEGF), interleukin (IL) 8, IL-10, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and receptor-interacting protein-2 (RIP2) in diffuse large B-cell lymphoma (DLBCL). Methods: A total of 68 DLBCL patients admitted to the Affiliated Hospital of Hebei Engineering University from January 2017 to June 2021 were included in this retrospective analysis. Serum VEGF was detected by enzyme-linked immunosorbent assay, serum IL-8 and IL-10 were detected by chemiluminescent enzyme immunoassay, and expression of PIK3CA and RIP2 in tumors was detected by immunohistochemistry. The correlation between clinical features of DLBCL and tumor-related index were analyzed. Cox regression was conducted to explore risk factors and hazard ratio. Results: The serum level or expressions of VEGF, IL-8, IL-10, and RIP2 were significantly elevated with the increase of Ann Arbor Stage, International Prognostic Index (IPI) scores, Eastern Cooperative Oncology Group (ECOG) scores, serum lactate dehydrogenase (LDH) level, and the number of extranodal sites (all P < 0.05). Beside, these serum indexes were significantly higher in patients with the presence of extranodal involvement and germinal center B-cell (GCB), but significantly lower in patients with the presence of bone marrow involvement (all P < 0.05). Cox regression analysis for overall survival revealed that high expression of VEGF, high level of serum IL-8, serum IL-10, and RIP2, Ann Arbor Stage (III-IV), number of extranodal sites (>1), serum LDH level (≥245 U/L), IPI scores (3-5), ECOG scores (≥2), and bone marrow involvement were independent risk factors for the prognosis of DLBCL patients (all P < 0.05). Conclusion: The serum levels of VEGF, IL-8, and IL-10, as well as the expression of RIP2 and PIK3CA in tumor tissues, were highly correlated to clinical features of DLBCL, and high expression level of these indexes may have adverse effects for the prognosis of DLBCL patients.

Dual Inhibition of BMP and WNT Signals Promotes Pancreatic Differentiation from Human Pluripotent Stem Cells.

Pathological or functional loss of pancreatic beta cells is the cause of diabetes. Understanding how signaling pathways regulate pancreatic lineage and searching for combinations of signal modulators to promote pancreatic differentiation will definitely facilitate the robust generation of functional beta cells for curing hyperglycemia. In this study, we first tested the effect of several potent BMP inhibitors on pancreatic differentiation using human embryonic stem cells. Next, we examined the endodermal lineage bias upon potent BMP inhibitor treatment and further checked the crosstalk between signal pathways governing endodermal lineage determination. Furthermore, we improved current pancreatic differentiation system based on the signaling pathway study. Finally, we used human-induced pluripotent stem cells to validate our finding. We found BMP inhibitors indeed not only blocked hepatic lineage but also impeded intestinal lineage from human definitive endoderm unexpectedly. Signaling pathway analysis indicated potent BMP inhibitor resulted in the decrease of WNT signal activity and inhibition of WNT could contribute to the improved pancreatic differentiation. Herein, we combined the dual inhibition of BMP and WNT signaling and greatly enhanced human pancreatic progenitor differentiation as well as beta cell generation from both embryonic stem cells and induced pluripotent stem cells. Conclusively, our present work identified the crosstalk between the BMP and WNT signal pathways during human endoderm patterning and pancreas specification, and provided an improved in vitro pancreatic directed differentiation protocol from human pluripotent stem cells.

Hierarchical microspheres with macropores fabricated from chitin as 3D cell culture.

3D cell culture is an urgent requirement for large-scale cell manufacture and structure-based tissue engineering; however, their preparation is still challenging due to the lack of a highly biocompatible culture environment for various types of cells. The excellent biocompatibility of chitin derived from crabs and shrimps has been proved before. Herein, for the first time, we designed and prepared hierarchical chitin microspheres with open tunable macropores using chitosan microspheres as a sacrificial template, based on their selective solubility. In our findings, the chitosan microspheres with various sizes were embedded in the chitin microsphere fabricated from NaOH/urea aqueous solution, and then were removed using a weak acid to form macropores with mean pore sizes of 63 µm, 94 µm and 135 µm. Importantly, the chitin microspheres having an average diameter of 240 µm with the macroporous structure exhibited good strength, as a result of the existence of nanofibrous networks. The chitin nanofibers played important roles in both enhancing the mechanical properties of PCMS and improving the adhesion, growth, and proliferation of cells due to the inherent bioactivity of chitin. Moreover, the chitin macroporous microspheres could support the growth of various mammalian cells, such as monkey fibroblasts, human hepatocytes and even human stem cells. The stem cells cultured in this microsphere maintained their 3D structure and multi-lineage differentiation capacity. This study provides a new "bottom-up" approach to create macroporous microspheres from a chitin solution, which could be used for large-scale human stem cell 3D culture and also as a promising candidate for the fabrication of excellent scaffolds.