BackgroundRecent studies show that C-reactive protein (CRP) is not only a biomarker but also a pathogenic mediator contributing to the development of inflammation and ageing-related diseases. However, serum levels of CRP in the healthy ageing population remained unclear, which was investigated in the present study.MethodsSerum levels of high sensitive C-reactive protein (hs-CRP), glucose (Glu), triglyceride (TG), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), superoxide dismutase (SOD), serum creatinine (SCr), serum uric acid (SUA) were measured in 6060healthy subjects (3672 male and 2388 female, mean age:45.9 years) who received routine physical examination at Sun Yat-sen Memorial Hospital, Guangzhou, China.ResultsIn total of 6060 healthy people, serum levels of hs-CRP were significantly increased with ageing (P < 0.05), particularly in those with age over 45-year-old (1.31[0.69–2.75] vs 1.05[0.53–2.16]mg/L, P < 0.001). Interestingly, levels of serum hs-CRP were significantly higher in male than female population (1.24[0.65–2.57] vs 1.07[0.53–2.29]mg/L, P < 0.001). Correlation analysis also revealed that serum levels of hs-CRP positively correlated with age and SUA, but inversely correlated with serum levels of HDL-c and SOD (all P < 0.05).ConclusionsBaseline levels of serum hs-CRP are increased with ageing and are significantly higher in male than female healthy population. In addition, elevated serum levels of hs-CRP are also associated with increased SUA but decreased HDL-c and SOD. Thus, serum levels of hs-CRP may be an indicator associated with ageing in healthy Chinese population.Electronic supplementary materialThe online version of this article (10.1186/s12979-018-0126-7) contains supplementary material, which is available to authorized users.
Background Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer with exceedingly poor prognosis, and chemoresistance is a huge challenge for treatment. N6‐methyladenosine (m 6 A) modification plays an important role in the progression and chemoresistance of cancers. We aimed to investigate the oncogenic function and therapeutic significance of the m 6 A binding protein, YTH domain family 2 (YTHDF2), in ICC progression and cisplatin‐based chemotherapy. Methods Several independent data sets were used to assess the expression of YTHDF2 in ICC, particularly in chemoresistant ICC. Knockdown and overexpression were used to evaluate the effects of YTHDF2 on tumourigenesis and cisplatin response in ICC. Multi‐omics sequencing was performed to identify target genes. RIP, dual luciferase reporter, RNA stability experiment and loss‐of‐function assays were conducted to study the mechanisms underlying the oncogenic function of YTHDF2. Furthermore, patient‐derived xenograft (PDX) model was established to determine the effect of combination treatment of YTHDF2 siRNA and cisplatin in ICC. Results Our study showed that YTHDF2 was upregulated in ICC tissues, particularly in chemoresistant ICC tissues, and correlated with poor prognosis. Furthermore, silencing YTHDF2 led to inhibited proliferation, promoted apoptosis and G0/G1 cell cycle arrest. Its downregulation also enhanced DNA damage and sensitised ICC cells to cisplatin. YTHDF2 overexpression exerted the opposite results. Integration analysis using RNA‐seq, MeRIP‐seq and anti‐YTHDF2 RIP‐seq elucidated the role of YTHDF2 in tumourigenesis and cisplatin‐desensitising function by promoting the degradation of cyclin‐dependent kinase inhibitor 1B (CDKN1B) mRNA in an m 6 A‐dependent manner. Downregulation of CDKN1B increased the YTHDF2 silencing‐induced influence on tumourigenesis and cisplatin response to ICC. In addition, the combination treatment of YTHDF2 siRNA and cisplatin significantly enhanced the anti‐tumour effect of cisplatin in a chemoresistant ICC PDX model. Conclusions YTHDF2 exhibits tumour oncogenic and cisplatin‐desensitising properties, which may offer insight into the development of novel combination therapeutic strategies for ICC.
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