Association Between Transforming Growth Factor-ß1 Polymorphisms and Ischemic Stroke Susceptibility: A Meta-Analysis.

Epidemiological studies have suggested a potential relationship between the transforming growth factor-ß1 (TGF-ß1) gene and ischemic stroke (IS) risk; however, the current results are inconsistent. Therefore, we performed this meta-analysis to assess the precise association between TGF-ß1 polymorphisms and IS risk. Online databases were searched for themes related to TGF-ß1 polymorphisms and ARE risk. Quantitative calculations of odds ratios (ORs) and confidence intervals (CIs) were performed using 5 genetic models of each variant locus. Heterogeneity tests, cumulative analyses, sensitivity analyses, and publication bias were conducted to examine statistical power. Moreover, changes in the secondary structure and minimum free energy (MFE) were explored using in silico analysis. Nineteen case-control studies were included in our meta-analysis on rs1800468 G>A, rs1800469 C>T, and rs1800470 T>C polymorphisms and IS risk. Overall, only a marginal association was found between the rs1800469 C>T polymorphism and IS risk (T vs C: OR = 1.12, 95%CI = 1.00-1.46, P = .05, I2 = 77.0%). Otherwise, no significant association was observed between the rs1800468 G>A and rs1800470 T>C polymorphisms and IS risk in general and stratified analyses. Moreover, no significant changes in secondary structure and MFE were found in any of the 3 polymorphic loci. Current evidence cautiously suggests that TGF-ß1 polymorphisms are not associated with IS susceptibility.

ATPR triggers acute myeloid leukaemia cells differentiation and cycle arrest via the RARα/LDHB/ERK-glycolysis signalling axis.

Acute myeloid leukaemia (AML) remains a therapeutic challenge and improvements in chemotherapy are needed. 4-Amino-2-trifluoromethyl-phenyl retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, has been proven to show superior anticancer effect compared with ATRA on various cancers. However, its potential effect on AML remains largely unknown. Lactate dehydrogenase B (LDHB) is the key glycolytic enzyme that catalyses the interconversion between pyruvate and lactate. Currently, little is known about the role of LDHB in AML. In this study, we found that ATPR showed antileukaemic effects with RARα dependent in AML cells. LDHB was aberrantly overexpressed in human AML peripheral blood mononuclear cell (PBMC) and AML cell lines. A lentiviral vector expressing LDHB-targeting shRNA was constructed to generate a stable AML cells with low expression of LDHB. The effect of LDHB knockdown on differentiation and cycle arrest of AML cells was assessed in vitro and vivo, including involvement of Raf/MEK/ERK signalling. Finally, these data suggested that ATPR showed antileukaemic effects by RARα/LDHB/ ERK-glycolysis signalling axis. Further studies should focus on the underlying leukaemia-promoting mechanisms and investigate LDHB as a therapeutic target.