ABSTRACT
Objective@#To analyze changes in proteoglycan and its correlation with alveolar bone resorption in periodontitis. @*Methods @#Twelve eight-week-old C57BL/6J male mice were selected, and the periodontitis model was established by ligating the right maxillary second molar with 6-0 silk thread. The nonligated part of the left maxilla was used as the control. The mice were killed 14 days after the operation. Micro-CT was used to assess alveolar bone resorption. HE staining was used to observe the alveolar bone profile, and TRAP staining was conducted to examine the positive rate of osteoclasts. The expression of proteoglycan-related genes, such as aggrecan (ACAN), biglycan (BGN), versican (VCAN), decorin (DCN), osteoclast-related genes, such as cathepsin K (CTSK), matrix metalloprotein-9 (MMP-9), and receptor activator of nuclear factor kappa-B ligand (RANKL), and inflammation-related genes, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), was detected by real-time quantitative PCR. Additionally, the correlation of the expression of proteoglycans with osteoclast-related genes and inflammation-related genes was evaluated by Pearson correlation analysis.@* Results@#The resorption of alveolar bone on the periodontitis side increased. TRAP staining showed that the number of osteoclasts was substantially increased in the maxilla with periodontitis. Real-time quantitative PCR demonstrated that compared with the control side, the expression of proteoglycan-related genes, such as ACAN, BGN, and DCN, was decreased, whereas the expression of the VCAN gene was significantly increased in the periodontitis side. Meanwhile, the expression of osteoclast-related genes, such as CTSK, MMP-9, and RANKL, and inflammation-related genes, such as IL-1β, IL-6, and TNF-α, was markedly increased in the periodontitis side (P<0.05). Pearson correlation analysis indicated a negative correlation between the expression of proteoglycans and the mRNA levels of osteoclast-related genes and inflammation-related genes (P<0.05). @*Conclusion @#The expression of proteoglycan was closely related to alveolar bone resorption in a periodontitis model.
ABSTRACT
@#[Abstract] Objective: To investigate the effect of lncRNA MAFG-AS1/ miR-11181-3p/GLG1 axis on cell migration, invasion and aerobic glycolysis of gastric cancer (GC) cells and its possible mechanism. Methods: AGS, a GC cell line with relatively high expression of MAFG-AS1, was selected as the study object. qPCR was used to detect RNA expression levels of MAFG-AS1, miR-11181-3p and GLG1. Transwell and glycolysis analysis were used to investigate cell migration, invasion and aerobic glycolysis. Bioinformatics analysis and Dual luciferase reporter gene assay were used to analyze the interaction among MAFG-AS1, miR-11181-3p and GLG1. Results: Knockdown of MAFG-AS1 significantly up-regulated miR-11181-3p and down-regulated GLG1 expression (both P<0.01), and significantly inhibited migration, invasion and aerobic glycolysis of GC cells (all P<0.01). Luciferase reporter gene assay confirmed that MAFG-AS1 competitively sponged miR-11181-3p (P<0.01). Inhibition of miR-11181-3p or overexpression of GLG1 partially reversed the inhibitory effect of MAFG-AS1 knockdown on GC cell migration, invasion, and aerobic glycolysis (all P<0.05 or P<0.01). Conclusion: MAFG-AS1 promotes cell migration, invasion and aerobic glycolysis of GC cells via miR-11181-3p/GLG1 axis, and may be a potential molecular target for GC diagnosis and therapy.
ABSTRACT
@#Objective: To investigate the effect of Notch4 regulatingATF2 (activating transcription factor 2) on the invasion and migration of pancreatic cancer (PC) cells and its possible mechanism. Methods:Atotal of 60 pairs of PC tissues and corresponding para-cancerous tissues that surgically resected at Taizhou University Hospital during February 2015 and July 2019 were collected for this study. The expression of Notch4 was detected by immunohistochemistry. siRNA technology was used to knock down Notch4 gene expression in PC cell lines (MiaPaCa-2 and PANC-1). Transwell assay was used to analyze the effect of Notch4 knockdown on cell invasion and migration. qPCR and Western blotting (WB) were used to detect the effects of Notch4 knockdown on mRNA and protein expressions of Notch4 and ATF2. Results: Compared with para-cancerous tissues, the expression of Notch4 in PC tissues significantly higher (P<0.01). After Notch4 siRNA transfection, the mRNA and protein expressions of Notch4 and ATF2 in MiaPaCa-2 and PANC-1 cells significantly decreased (all P<0.01). Compared with Control siRNA group, the migration and invasion ability of PC cells in Notch4 siRNA groupsignificantlyreduced(allP<0.01).Conclusion:Notch4ishighlyexpressedinPCtissues.Knockdown of Notch4 can down-regulate the expression ofATF2 at the transcriptional level, thereby inhibiting the invasion and migration ability of PC cells.
ABSTRACT
@#Chimeric antigen receptor T-cell (CAR-T) targeting CD19 has made significant progress in the treatment of B cell malignancies. FDA has approved two CD19 CAR-T therapeutic products. With the development in the clinical and mechanism research of immunotherapy (CAR-T, bispecific T-cell engager [BiTE]), dual affinity re-targeting [DART], and genetically modified T cell receptorT cell [TCR-T]), its potential risks and side effects have been more widely recognized, especially cytokine release syndrome (CRS). CRS is currently the most common complication after CAR-T treatment and can be life-threatening in severe cases. Moreover, the pathophysiological process of CRS is complex, involving a variety of immune cells and non-immune cells, and can affect whole body organs. Elucidating the mechanisms of CRS development is of great significance to improve the safety of CAR-T therapy. In recent years, researchers have conducted study in animal models to illustrate the mechanisms of CRS more deeply. This review discusses the development, pathophysiological mechanisms, animal models, clinical features, and graded treatments of CRS, aiming to provide an in-depth understanding of the mechanism of CRS and improve the safety of CAR-T therapy.
ABSTRACT
@# Cell therapy includes stem cell therapy and immunotherapy for multiple diseases including cancer. With the progress in life science and medicine as well as people’s increasing demands for health, cell therapy has become an important frontier research field. Constantly emerged innovative theories, technologies and clinical outcomes of cell therapy have laid a solid foundation for the development of cell therapy industrialization. Now some cell therapy products have already been approved by the regulatory authorities abroad; and in China, cell therapy is in a period of great opportunities. Therefore, how to optimize the supervision and guiding system and provisions, to better stimulate the vitality of research and transformation, to create more benefits for patients and to promote the development of the industry in an orderly manner have become an issues that worth deep consideration. In this paper, we discussed the current progress on stem cell therapy and immunotherapy represented by chimeric antigen receptor T-Cell (CAR-T) in both domestic and overseas, and the industry supervision of cell therapy in China; in addition, we also put forward some suggestions for the development of cell therapy in China for the reference of peers in this field.