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BACKGROUND Homocysteine-lowering intervention with folate was recently shown to be able to increase day-night difference of blood pressure (BP) in humans indicating a potential relationship between homocysteine and circadian BP variation. We thus sought to investigate the association between plasma total homocysteine level (tHcy) and circadian BP variation in hypertensive adults. METHODS We enrolled 244 eligible dipping and 249 nondipping BP status adults from 560 adults who were randomly sampled from 5,233 Chinese hypertensive adults who received ambulatory BP monitoring (ABPM). We further enrolled 390 adults with CC/CT genotypes of the methylenetetrahydrofolate reductase (MTHFR) and 79 TT genotype who received ABPM at the same time from 1858 hypertensive adults with MTHFR polymorphisms detection. RESULTS Plasma tHcy in nondippers was significantly higher than dippers (P < 0.001). Simple linear analysis revealed that tHcy significantly correlated with nocturnal systolic BP fall (r = -0.145, P = 0.001) and diastolic BP fall (r = -0.141, P = 0.002). Multivariate logistic regression analysis further identified tHcy as an independent factor correlated with the presence of nondipping BP status in hypertensive adults (odds ratio: 1.873, 95% confidence interval: 1.171-2.996, P = 0.009). The percentage of dipping BP status was 19.49% or 8.86% and the percentage of nondipping BP status was 80.51% or 91.14% in CC/CT or TT genotypes, respectively. The above different between CC/CT and TT genotypes was significant (P = 0.024). CONCLUSIONS These results indicated that high homocysteine levels associate with disturbed circadian BP variation in Chinese hypertensive adults.

Chlorogenic acid (CGA) exhibits various biological properties, including the inhibition of oxidation, obesity, apoptosis and tumorigenesis. CGA is also able to promote cell survival and proliferation. The aim of the present study was to determine the effects and underlying molecular mechanisms of CGA on the adipogenesis of bone marrow‑derived mesenchymal stem cells (BMSCs). Treatment with CGA had a marginal effect on cell proliferation, by promoting the expression levels of phosphorylated Akt and cyclin D1. Furthermore, treatment with CGA also upregulated the phosphorylation of extracellular signal‑regulated kinase (Erk) and inhibited the adipocyte differentiation of BMSCs by inhibiting the expression of peroxisome proliferator‑activated receptor (PPAR)γ and CCAAT/enhancer binding protein (C/EBP)α. However, knockdown of the expression of Shp2 attenuated CGA‑induced proliferation and inhibited the phosphorylation of Akt and expression of cyclin D1. Furthermore, CGA treatment upregulated Erk phosphorylation and decreased the expression levels of PPARγ and CEBPα, which was inhibited by treatment with the Shp2 PTPase activity inhibitor, NSC‑87877. The results of the present study suggested that CGA‑induced Akt and Erk pathways regulate proliferation and differentiation and that Shp2 is important in the proliferation and differentiation of BMSCs.

To investigate the inhibitory effects of antisense oligonucleotides to different sequences on VEGF gene expression by human hepatoma cells.SMMC7721 cells were cultured under normoxic or hypoxic conditions for 24 h, followed by being transfected with different antisense oligonucleotides (A06513 to cap structure, A06514 to translation initiation, A06515 to Exon-3 and A06516 to translation terminal). The total RNAs from the cells were extracted and the VEGF expression were examined with RT-PCR. The relative concentrations of VEGF transcripts in SMMC772 cells from different groups were determined using GAPDH (glyceraldehyde-3-phosphate dehydrogenase) cDNA as internal standard.In response to the hypoxic challenge, SMMC7721 cells upregulated VEGF mRNA; Comparative to the control (no oligonucleotides), A06513, A06514, A06515, and A06516 had obvious sequence-specific inhibitory effect on VEGF gene expression, with the ratio of VEGF over GAPDH of 0.49+/-0.08, 0.71+/-0.12, 0.72+/-0.11 and 0.86+/-0.12, respectively (F=12.21, P0.05). A06513 showed the strongest inhibitory effect (P0.01).The antisense oligonucleotides complementary to VEGF cap structure, may become a potential alternative for antisense gene therapy of HCC.