Objective:To investigate the effects of icaritin(ICT)on the proliferation and osteogenic differentiation of rat bone mar-row stromal cells(rBMSCs).Methods:rBMSCs were cultured from the bone marrow of SD rats and identified by multilineage differ-entiation assays.3,6 and 9 days after the treatment of rBMSCs of passage 4 by ICT at 1 0 -9 ,1 0 -8 ,1 0 -7 ,1 0 -6 and 1 0 -5 mol/L re-spectively,the proliferation and differentiation of the cells were examined by cck-8 and alkaline phosphatase (ALP)activity assay kit respectively.The calcium nodule formation was observed by alizarin red(AR)staining 21 days after 1 0 -9 mol/L ICT treatment. Results:Primary rBMSCs showed the typical spindle-like shape with attachment growth.rBMSCs could be induced to osteogenic and adipogenic differentiation.The proliferation of rBMSCs was inhibited but ALP activity was enhanced by ICT.1 0 -9 mol/L ICT in-cresed calcium nodule formation.Conclusion:ICT can dose-dependently inhibit the proliferation,but promote the osteogenic differ-entiation of rBMSCs.

BACKGROUND: A polygenic risk score (PRS) derived from 112 single-nucleotide polymorphisms (SNPs) for gastric cancer has been reported in Chinese populations (PRS-112). However, its performance in other populations is unknown. A functional PRS (fPRS) using functional SNPs (fSNPs) may improve the generalizability of the PRS across populations with distinct ethnicities. METHODS: We performed functional annotations on SNPs in strong linkage disequilibrium (LD) with the 112 previously reported SNPs to identify fSNPs that affect protein-coding or transcriptional regulation. Subsequently, we constructed an fPRS based on the fSNPs by using the LDpred2-infinitesimal model and then analyzed the performance of the PRS-112 and fPRS in the risk prediction of gastric cancer in 457,521 European participants of the UK Biobank cohort. Finally, the performance of the fPRS in combination with lifestyle factors were evaluated in predicting the risk of gastric cancer. RESULTS: During 4,582,045 person-years of follow-up with a total of 623 incident gastric cancer cases, we found no significant association between the PRS-112 and gastric cancer risk in the European population (hazard ratio [HR] = 1.00 [95% confidence interval (CI) 0.93-1.09], P = 0.846). We identified 125 fSNPs, including seven deleterious protein-coding SNPs and 118 regulatory non-coding SNPs, and used them to construct the fPRS-125. Our result showed that the fPRS-125 was significantly associated with gastric cancer risk (HR = 1.11 [95% CI, 1.03-1.20], P = 0.009). Compared to participants with a low fPRS-125 (bottom quintile), those with a high fPRS-125 (top quintile) had a higher risk of incident gastric cancer (HR = 1.43 [95% CI, 1.12-1.84], P = 0.005). Moreover, we observed that participants with both an unfavorable lifestyle and a high genetic risk had the highest risk of incident gastric cancer (HR = 4.99 [95% CI, 1.55-16.10], P = 0.007) compared to those with both a favorable lifestyle and a low genetic risk. CONCLUSION These results indicate that the fPRS-125 derived from fSNPs may act as an indicator to measure the genetic risk of gastric cancer in the European population.
Humans ; Prospective Studies ; Stomach Neoplasms/genetics* ; Genetic Predisposition to Disease/genetics* ; Risk Factors ; Multifactorial Inheritance/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Genome-Wide Association Study